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13105230 Clinical Drug Therapeutic Nursing

13105230 Clinical Drug Therapeutic Nursing

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Publicado porPopa D. Silviu

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Published by: Popa D. Silviu on May 29, 2013
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  • Anesthetics
  • Drugs Affecting the Endocrine System
  • Nutrients, Fluids, and Electrolytes
  • Drugs Used to Treat Infections



Introduction to Drug Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1 Introduction to Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
A Message to Students 2 Overview 2 Sources of Drugs 3 Drug Classifications and Prototypes 3 Drug Names 3 Drug Marketing 3 Pharmacoeconomics 4 Prescription and Nonprescription Drugs 4 Drug Approval Processes 4 Sources of Drug Information 7 Strategies for Studying Pharmacology 7


Basic Concepts and Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Overview 9 Cellular Physiology 9 Drug Transport Through Cell Membranes 10 Pharmacokinetics 10 Pharmacodynamics 15 Variables That Affect Drug Actions 17 Tolerance and Cross-Tolerance 20 Adverse Effects of Drugs 20


Administering Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Overview 29 General Principles of Accurate Drug Administration Legal Responsibilities 30 Medication Errors 30 Medication Systems 31 Medication Orders 31 Drug Preparations and Dosage Forms 32 Calculating Drug Dosages 34 Routes of Administration 35 29


Nursing Process in Drug Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Overview 47 Nursing Process in Drug Therapy 48 Integrating Nursing Process, Critical Paths and Drug Therapy General Principles of Drug Therapy 59 51





Drugs Affecting the Central Nervous System
Characteristics and Functions of the Central Nervous System Drugs Affecting the Central Nervous System 77 72

. . . . . . . . . . . 71

Physiology of the Central Nervous System . . . . . . . . . . . . . . . . . . . . . . 72


Opioid Analgesics and Opioid Antagonists . . . . . . . . . . . . . . . . . . . . . 79
Overview 79 Pain 79 Endogenous Analgesia System Opioid Analgesics 80 Individual Drugs 82 Principles of Therapy 89 80


Analgesic–Antipyretic–Anti-inflammatory and Related Drugs . . . . . 99
Overview 99 Pain, Fever, and Inflammation 100 Mechanism of Action 100 Indications for Use 102 Contraindications to Use 103 Subgroups and Individual Drugs 104 Principles of Therapy 114


Antianxiety and Sedative-Hypnotic Drugs . . . . . . . . . . . . . . . . . . . . . 124
Overview 124 Anxiety 125 Sleep and Insomnia 125 Drugs Used to Treat Anxiety and Insomnia Principles of Therapy 134



Antipsychotic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
Psychosis 144 Schizophrenia 145 Antipsychotic Drugs 145 Principles of Therapy 152


Drugs for Mood Disorders: Antidepressants and Mood Stabilizers . . . . . . . . . . . . . . . . . . . . . . . . 163
Mood Disorders 163 Antidepressant Drugs 165 Types of Antidepressants and Individual Drugs Principles of Therapy 171 166


Antiseizure Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
Seizure Disorders 182 Antiseizure Drugs 183 Individual Antiseizure Drugs Principles of Therapy 193 184




Antiparkinson Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
Parkinson’s Disease 202 Antiparkinson Drugs 202 Individual Antiparkinson Drugs Principles of Therapy 207 203


Skeletal Muscle Relaxants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
Skeletal Muscle Relaxants 213 Individual Drugs 214 Principles of Therapy 217


Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
General Anesthesia 220 Regional Anesthesia 221 Adjuncts to Anesthesia 221 Individual Anesthetic Agents 222 Principles of Therapy 222


Substance Abuse Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
Substance Abuse 236 Dependence 236 Central Nervous System Depressants 237 Central Nervous System Stimulants 243 Principles of Therapy 249


Central Nervous System Stimulants . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Uses 251 Types of Stimulants 252 Individual Central Nervous System Stimulants Principles of Therapy 255 252


Drugs Affecting the Autonomic Nervous System
Autonomic Nervous System 261 Characteristics of Autonomic Drugs

. . . . . . 260

Physiology of the Autonomic Nervous System . . . . . . . . . . . . . . . . . . 261


Adrenergic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
Description 268 Individual Adrenergic Drugs 272 Principles of Therapy 275


Antiadrenergic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
Description 283 Individual Antiadrenergic Drugs Principles of Therapy 290 285




Cholinergic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
Description 298 Individual Cholinergic Drugs Principles of Therapy 303 299


Anticholinergic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308
Description 308 Individual Anticholinergic Drugs Principles of Therapy 314 310


Drugs Affecting the Endocrine System
Overview 321 Endocrine System–Nervous System Interactions 321 General Characteristics of Hormones 322 General Characteristics of Hormonal Drugs 324

. . . . . . . . . . . . . . . . . 320

Physiology of the Endocrine System . . . . . . . . . . . . . . . . . . . . . . . . . . 321


Hypothalamic and Pituitary Hormones . . . . . . . . . . . . . . . . . . . . . . . 325
Overview 325 Therapeutic Limitations 327 Individual Hormonal Agents 328 Principles of Therapy 331


Corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
Overview 334 Endogenous Corticosteroids 334 Exogenous Corticosteroids (Glucocorticoid Drugs) Principles of Therapy 343 337


Thyroid and Antithyroid Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
Overview 353 Thyroid Disorders 354 Individual Drugs 356 Principles of Therapy 360


Hormones That Regulate Calcium and Bone Metabolism . . . . . . . . 366
Overview 366 Drugs Used for Calcium and Bone Disorders Principles of Therapy 375 368


Antidiabetic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382
Overview 382 Endogenous Insulin 382 Diabetes Mellitus 384 Hypoglycemic Drugs 385 Principles of Therapy 394




Estrogens, Progestins, and Hormonal Contraceptives . . . . . . . . . . . 409
Overview 409 Estrogens 410 Progesterone 410 Estrogens and Progestins Used as Drugs 411 Individual Estrogens, Progestins, and Combination Products Principles of Therapy 418



Androgens and Anabolic Steroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425
Overview 425 Testosterone 425 Anabolic Steroids 426 Abuse of Androgenic and Anabolic Steroid Drugs 426 Androgens and Anabolic Steroids Used As Drugs 427 Principles of Therapy 429


Nutrients, Fluids, and Electrolytes . . . . . . . . . . . . . . . . . . . . . . 433
30 Nutritional Support Products and Drugs for Obesity . . . . . . . . . . . . 434
Overview 434 Nutritional Deficiency States Nutritional Products 435 Pancreatic Enzymes 435 Obesity 436 Principles of Therapy 442 434


Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453
Overview 453 Description and Uses 454 Vitamin Supplements 454 Principles of Therapy 460


Minerals and Electrolytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469
Overview 469 Minerals as Nutrients 470 Individual Agents Used In Mineral–Electrolyte Imbalances Principles of Therapy 483 470


Drugs Used to Treat Infections
Overview 494 Microorganisms and Infections 494 Host Defense Mechanisms 499 Characteristics of Anti-Infective Drugs Principles of Therapy 502

. . . . . . . . . . . . . . . . . . . . . . . . . . 493

General Characteristics of Antimicrobial Drugs . . . . . . . . . . . . . . . . 494





Beta-Lactam Antibacterials: Penicillins, Cephalosporins, and Others . . . . . . . . . . . . . . . . . . . . . . 510
Overview 510 Penicillins 511 Cephalosporins 517 Carbapenems 518 Monobactam 519 Principles of Therapy 519


Aminoglycosides and Fluoroquinolones . . . . . . . . . . . . . . . . . . . . . . 527
Overview 527 Aminoglycosides 527 Fluoroquinolones 530 Principles of Therapy 531


Tetracyclines, Sulfonamides, and Urinary Agents . . . . . . . . . . . . . . 537
Overview 537 Principles of Therapy 543


Macrolides and Miscellaneous Antibacterials . . . . . . . . . . . . . . . . . . 548
Overview 548 Macrolides 548 Miscellaneous Antibacterial Drugs Principles of Therapy 552 550


Drugs for Tuberculosis and Mycobacterium avium Complex (MAC) Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
Overview 559 Epidemiology of Tuberculosis 560 Drug-Resistant Tuberculosis 561 Preventing the Development and Spread of Tuberculosis Antitubercular Drugs 561 Treatment of Active Tuberculosis 567 Mycobacterium avium Complex Disease 567 Principles of Therapy 568



Antiviral Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 576
Overview 576 Principles of Therapy 585


Antifungal Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595
Overview 595 Fungal Infections 596 Principles of Therapy 606


Antiparasitics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 614
Overview 614 Protozoal Infections 614 Helminthiasis 616 Scabies and Pediculosis 616 Antiparasitic Drugs 617 Principles of Therapy 623




Drugs Affecting Hematopoiesis and the Immune System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 627
42 Physiology of the Hematopoietic and Immune Systems . . . . . . . . . . 628
Overview 628 Hematopoietic Cytokines 628 Overview of Body Defense Mechanisms 630 Immunity 631 Immune Cells 632 Patient-Related Factors That Influence Immune Function 637 Immune Disorders 638 Drugs That Alter Hematopoietic and Immune Responses 638


Immunizing Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 640
Overview 640 Immunization 641 Agents for Active Immunity 641 Agents for Passive Immunity 641 Individual Immunizing Agents 642 Principles of Therapy 648


Hematopoietic and Immunostimulant Drugs . . . . . . . . . . . . . . . . . . . 657
Overview 657 General Characteristics of Hematopoietic and Immunostimulant Drugs Principles of Therapy 663 657


Immunosuppressants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 671
Overview 671 Autoimmune Disorders 672 Tissue and Organ Transplantation Immunosuppressant Drugs 675 Principles of Therapy 682 674


Drugs Affecting the Respiratory System
Overview 694 Summary 696 Disorders of the Respiratory System Drug Therapy 696

. . . . . . . . . . . . . . . 693

Physiology of the Respiratory System . . . . . . . . . . . . . . . . . . . . . . . . . 694


Drugs for Asthma and Other Bronchoconstrictive Disorders . . . . . 697
Overview 697 Drug Therapy 700 Principles of Therapy 706




Antihistamines and Allergic Disorders . . . . . . . . . . . . . . . . . . . . . . . . 715
Overview 715 Histamine and Its Receptors 715 Hypersensitivity (Allergic) Reactions Antihistamines 718 Principles of Therapy 723 716


Nasal Decongestants, Antitussives, and Cold Remedies . . . . . . . . . . 728
Overview 728 The Common Cold 728 Sinusitis 729 Common Signs and Symptoms of Respiratory Disorders Drugs for Respiratory Disorders 729 Individual Drugs 730 Principles of Therapy 733



Drugs Affecting the Cardiovascular System
Overview 739 Heart 739 Blood Vessels 740 Blood 741 Cardiovascular Disorders 742 Drug Therapy in Cardiovascular Disorders

. . . . . . . . . . . 738

Physiology of the Cardiovascular System . . . . . . . . . . . . . . . . . . . . . . 739



Drug Therapy of Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 743
Overview 743 Drug Therapy 744 Principles of Therapy 750


Antidysrhythmic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 758
Overview 758 Cardiac Electrophysiology 758 Cardiac Dysrhythmias 759 Antidysrhythmic Drugs 760 Classifications and Individual Drugs Principles of Therapy 767



Antianginal Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 774
Overview 774 Antianginal Drugs 777 Principles of Therapy 782


Drugs Used in Hypotension and Shock . . . . . . . . . . . . . . . . . . . . . . . 788
Overview 788 Antishock Drugs 789 Individual Drugs 789 Principles of Therapy 792




Antihypertensive Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 797
Overview 797 Regulation of Arterial Blood Pressure Hypertension 798 Antihypertensive Drugs 801 Individual Drugs 803 Principles of Therapy 804 797


Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 818
Overview 818 Renal Physiology 818 Alterations in Renal Function Diuretic Drugs 821 Principles of Therapy 824 821


Drugs That Affect Blood Coagulation . . . . . . . . . . . . . . . . . . . . . . . . 832
Overview 832 Hemostasis 833 Clot Lysis 833 Thrombotic and Thromboembolic Disorders 833 Drugs Used in Thrombotic and Thromboembolic Disorders Principles of Therapy 843



Drugs for Dyslipidemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 851
Overview 851 Atherosclerosis 851 Blood Lipids 852 Dyslipidemia 853 Initial Management of Dyslipidemia 853 Drug Therapy of Dyslipidemia 854 Principles of Therapy 857


Drugs Affecting the Digestive System . . . . . . . . . . . . . . . . . . . 863
59 Physiology of the Digestive System . . . . . . . . . . . . . . . . . . . . . . . . . . . 864
Overview 864 Organs of the Digestive System 864 Secretions of the Digestive System 866 Effects of Drugs on the Digestive System 866


Drugs Used for Peptic Ulcer and Acid Reflux Disorders . . . . . . . . . 867
Overview 867 Peptic Ulcer Disease 867 Types of Drugs 869 Principles of Therapy 875




Laxatives and Cathartics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 883
Overview 883 Defecation 883 Laxatives and Cathartics 884 Principles of Therapy 887


Antidiarrheals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 892
Overview 892 Antidiarrheal Drugs 893 Principles of Therapy 897


Antiemetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 902
Overview 902 Antiemetic Drugs 903 Principles of Therapy 907


Drugs Used in Special Conditions . . . . . . . . . . . . . . . . . . . . . . . 912
64 Drugs Used in Oncologic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . 913
Overview 913 Normal and Malignant Cells Cancer 914 Antineoplastic Drugs 916 Individual Drugs 919 Cytoprotectant Drugs 919 Principles of Therapy 920 913


Drugs Used in Ophthalmic Conditions . . . . . . . . . . . . . . . . . . . . . . . . 935
Overview 935 Disorders of the Eye 936 Types of Ophthalmic Drugs 937 Ophthalmic Drug Therapy 937 Individual Drugs 937 Principles of Therapy 938


Drugs Used in Dermatologic Conditions . . . . . . . . . . . . . . . . . . . . . . 949
Overview 949 Disorders of the Skin 950 Types of Dermatologic Drugs Individual Drugs 953 Principles of Therapy 957 952




Drug Use During Pregnancy and Lactation . . . . . . . . . . . . . . . . . . . 965
Overview 965 Pregnancy and Lactation 965 Maternal–Placental–Fetal Circulation 966 Drug Effects on the Fetus 966 Fetal Therapeutics 970 Maternal Therapeutics 970 Abortifacients 973 Tocolytics 973 Drugs Used During Labor and Delivery at Term 974 Neonatal Therapeutics 975 Principles of Therapy 976


Recently Approved and Miscellaneous Drugs . . . . . . . . . . . . . . . . . . 981

The International System of Units . . . . . . . . . . . . . . . . . . . . . . . . . . . 983

Therapeutic Serum Drug Concentrations for Selected Drugs . . . . . 984

Canadian Drug Laws and Standards . . . . . . . . . . . . . . . . . . . . . . . . . 985

Canadian Drug Names . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 986 INDEX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 995

The basic precepts underlying previous editions of Clinical Drug Therapy continue to guide the writing of this seventh edition. The overall purpose is to promote safe, effective, and rational drug therapy by: • Providing information that accurately reflects current practices in drug therapy. • Facilitating the acquisition, comprehension, and application of knowledge related to drug therapy. Application requires knowledge about the drug and the client receiving it. • Identifying knowledge and skills the nurse can use to smooth the interface between a drug and the client receiving it.

• Preventing the need for drug therapy, when possible, by promoting health and preventing
conditions that require drug therapy.

• Using appropriate and effective nonpharmacologic interventions instead of, or in conjunction with, drug therapy when indicated. When used with drug therapy, such interventions may promote lower drug dosage, less frequent administration, and fewer adverse effects. • Enhancing therapeutic effects by administering drugs accurately and considering clients’ individual characteristics that influence responses to drug therapy. • Preventing or minimizing adverse drug effects by knowing the major adverse effects associated with particular drugs, identifying clients with characteristics that may increase risks of experiencing adverse effects, and actively monitoring for the occurrence of adverse effects. When adverse effects occur, early recognition allows interventions to minimize their severity. Because all drugs may cause adverse effects, nurses must maintain a high index of suspicion that symptoms, especially new ones, may be drug-induced. • Teaching clients and caregivers about accurate administration of medications, nonpharmacologic treatments to use with or instead of pharmacologic treatments, and when to contact a health care provider.

The content of Clinical Drug Therapy is organized in 11 sections, primarily by therapeutic drug groups and their effects on particular body systems. This approach helps the student make logical connections between major drug groups and the conditions for which they are used. It also provides a foundation for learning about new drugs, most of which fit into known groups. The first section contains the basic information required to learn, understand, and apply drug knowledge. The chapters in this section include drug names, classifications, prototypes, costs, laws and standards, schedules of controlled substances, drug approval processes, and learning strategies (Chapter 1); cellular physiology, drug transport, pharmacokinetic processes, the receptor theory of drug action, types of drug interactions, and factors that influence drug effects on body tissues (Chapter 2); dosage forms and routes and methods of accurate drug administration (Chapter 3); and guidelines for using the nursing process in drug therapy and general principles of drug therapy (Chapter 4). Most drug sections include an initial chapter that reviews the physiology of a body system followed by several chapters that discuss drug groups used to treat disorders of that body system. The seven physiology review chapters are designed to facilitate understanding of drug effects on a



body system. These include the central nervous system; the autonomic nervous system; and the endocrine, hematopoietic, immune, respiratory, cardiovascular, and digestive systems. Other chapters within each section emphasize therapeutic classes of drugs and prototypical or commonly used individual drugs, those used to treat common disorders, and those likely to be encountered in clinical nursing practice. Drug chapter content is presented in a consistent format and includes a description of a condition for which a drug group is used; a general description of a drug group, including mechanism(s) of action, indications for use, and contraindications; and descriptions and tables of individual drugs, with recommended dosages and routes of administration. Additional clinically relevant information is presented under the headings of Nursing Process, Principles of Therapy, and Nursing Actions. The Nursing Process section emphasizes the importance of the nursing process in drug therapy, including assessment of the client’s condition in relation to the drug group, nursing diagnoses, expected outcomes, needed interventions, and evaluation of the client’s progress toward expected outcomes. Client teaching guidelines are displayed separately from other interventions to emphasize their importance. The Principles of Therapy section presents guidelines for individualizing drug therapy in specific populations (eg, children, older adults, clients with renal or hepatic impairments). General principles are included in Chapter 4; specific principles related to drug groups are included in the chapters where those drug groups are discussed. This approach, rather than separate chapters on pediatric and geriatric pharmacology, for example, was chosen because knowledge about a drug is required before that knowledge can be applied to a specific population with distinctive characteristics and needs in relation to drug therapy. Each drug chapter includes a Nursing Actions display that provides specific nursing responsibilities related to drug administration and client observation. Other drug sections include products used to treat nutritional, infectious, oncologic, ophthalmic, and dermatologic disorders.

• Updated Drug Information. More than 100 new drugs have been added. Some are additions to well-known drug groups, such as the angiotensin II receptor antagonists (Chapter 55); antidiabetic drugs (Chapter 27); antiretroviral drugs (Chapter 39); and drugs that affect blood coagulation (Chapter 57). Others represent advances in the drug therapy of some disease processes, such as newer anti-cancer agents (Chapter 64). In addition, continuing trends in drug dosage formulations are reflected in the increased numbers of fixed-dose combination drug products, long-acting preparations, and nasal or oral inhalation products. Major Revision of Many Chapters. Chapter revisions reflect current practices in drug therapy, integrate new drugs, explain the major characteristics of new drug groups, provide increased information about pharmacokinetics and toxicology, and add content related to herbal and dietary supplements when relevant to chapter content. Herbal and Dietary Supplements. Commonly used products are introduced in Chapter 4 and included in selected later chapters. Safety aspects are emphasized. New Tables. These include the conversion of all remaining drug monographs to a tabular format for drug dosages, tables of pharmacokinetic data for selected drug groups, a table of commonly overdosed drugs and their antidotes, and a table of commonly used herbal supplements. New Illustrations. Several new illustrations have been developed, primarily to enhance understanding of drug actions. New Boxed Displays. These include information to promote understanding of drug therapy for selected conditions.

• • • •

• Readability. Since the first edition of Clinical Drug Therapy was published in 1983, many
students and faculty have commented about the book’s clear presentation style.



• Organizational Framework. The book’s organizational framework allows it to be used
effectively as both a textbook and as a reference. As a textbook, students can read chapters in their entirety to learn the characteristics of major drug classes, their prototypical drugs or commonly used representatives, their uses and effects in prevention or treatment of disease processes, and their implications for nursing practice. As a reference book, students can readily review selected topics for classroom use or clinical application. Facilitating such uses are a consistent format and frequent headings that allow the reader to identify topics at a glance. Four-Color Design. The striking design enhances liveliness of the text and promotes student interest and interactivity. Interactive Displays. Presented in consistent formats and colors throughout the text, these displays heighten student attention and emphasize critical thinking and clinical decisionmaking skills. Drug-related chapters contain two or more of the following displays: an opening critical thinking scenario, a knowledge application situation, a medication error prevention exercise, and an ethical/legal dilemma. The solutions to the knowledge application situations and the medication error prevention exercises appear at the ends of chapters. Chapter Objectives. Learning objectives at the beginning of each chapter focus the student’s attention on important chapter content. Client Teaching Guidelines. This feature is designed to meet several goals. One is to highlight the importance of teaching clients and caregivers how to manage drug therapy at home, where most medications are taken. This is done by separating teaching from other nursing interventions. Another goal is to promote active and knowledgeable client participation in drug therapy regimens, which helps to maximize therapeutic effects and minimize adverse effects. In addition, written guidelines allow clients and caregivers to have a source of reference when questions arise in the home setting. A third goal is to make client teaching easier and less time consuming. Using the guidelines as a foundation, the nurse can simply add or delete information according to a client’s individual needs. To assist both the nurse and client further, the guidelines contain minimal medical jargon. Principles of Therapy. This unique section describes important drug-related and client-related characteristics that need to be considered in drug therapy regimens. Such considerations can greatly increase safety and therapeutic effects, and all health care providers associated with drug therapy should be aware of them. Most chapters contain principles with the headings of Use in Children, Use in Older Adults, Use in Renal Impairment, Use in Hepatic Impairment, and Home Care to denote differences related to age, developmental level, pathophysiology, and the home care setting. Some chapters include principles related to Genetic and Ethnic Considerations, Use in Critical Illness, and Management of Drug Toxicity or Drug Withdrawal. Nursing Actions Displays. These displays emphasize nursing interventions during drug therapy within the following categories: Administer accurately, Observe for therapeutic effects, Observe for adverse effects, and Observe for drug interactions. The inclusion of rationales for interventions provides a strong knowledge base and scientific foundation for clinical practice and critical thinking. Review and Application Exercises. Located at the end of each chapter, these questions encourage students to rehearse clinical application strategies in a nonclinical, nonstressful, nondistracting environment. They also promote self-testing in chapter content and can be used to promote classroom discussion. Answers to these exercises can be found on the connection companion Website http://connection.lww.com/go/abrams7e. Appendices. These include recently approved and miscellaneous drugs, the International System of Units, therapeutic serum drug concentrations for selected drugs, Canadian drug laws and standards, and Canadian drug names. Extensive Index. Listings of generic and trade names of drugs, nursing process, and other topics provide rapid access to desired information.

• •

• •

• •

Nursing students must develop skills in critical thinking, information processing, decision making, collaboration, and problem solving. How can a teacher assist students to develop these skills in relation to drug therapy? The goal of the ancillary package is to assist both student and teacher in this development.



The Study Guide engages the student’s interest and active participation by providing a variety of learning exercises and opportunities to practice cognitive skills. Worksheets promote the learning of concepts, principles, and characteristics and uses of major drug groups. The worksheets can be completed independently, by a small group as an in-class learning activity, or by the instructor, with answers elicited from the class as a whole. Clinical challenge scenarios promote appropriate data collection, critical analysis of both drug-related and client-related data, and application of the data in patient care. The connection companion Website http://connection.lww.com/go/abrams7e provides online updates for faculty and students, links to newly-approved drugs, answers to the chapter questions for review and application, and more. The free Back of Book CD-ROM is an invaluable learning tool that provides 3-D animated depictions of pharmacology concepts, video on preventing medication errors, NCLEX-style review questions, and monographs of the 100 most commonly prescribed drugs. The Instructor’s Resource CD-ROM facilitates use of the text in designing and implementing courses of study. To fulfill this purpose, the CD-ROM contains an Instructor’s Manual, an Electronic Testbank, and PowerPoint Slides. The Instructor’s Manual includes the following: • General observations and comments about teaching and learning pharmacology in relation to nursing • A sample syllabus for a separate three-credit hour, one-semester pharmacology course that may be taught in a traditional classroom or a nontraditional online setting • General teaching strategies for classroom or online teaching, with a listing of additional requirements for an online course (eg, a computer network and software such as WebCT or Blackboard; student computer skills and access to a computer; interactivity between students and faculty and among students; student preparation and participation; an online mechanism for submitting assignments, taking tests, and receiving grades; and modified teaching strategies) • Specific teaching strategies for classroom, online, small group, and clinical teaching of content in each chapter • A list of major topics; text locations of objectives, displays, and selected elements; terms and concepts; and selected individual drugs for each drug-related chapter of the text • Suggestions for designing an independent study course for RNs seeking a BSN • Suggestions for including pharmacology content in the nursing courses of an integrated curriculum. • Discussion/solutions of Clinical Challenges from the Study Guide • Drug Jeopardy Game, with a description and sample questions and answers The Brownstone® Testbank includes approximately 1,000 multiple-choice test items in NCLEX format, a Test Generator, and Grade Book. These materials can assist the instructor in evaluating students’ knowledge of drug information and their ability to apply that information in client care. PowerPoint slides include text and art from Clinical Drug Therapy to provide significant classroom or online teaching support. These varied materials allow each instructor to choose or adapt those relevant to his or her circumstances. The author and publisher hope the materials are truly helpful in easing the day-to-day rigors of teaching pharmacology, and invite comments from instructors regarding the materials. Anne Collins Abrams, RN, MSN

Sondra G. Ferguson, RN, MSN, CS, ANP, APRN, BC
Assistant Professor of Nursing Berea College Berea, Kentucky Chapters 50, 51, 55, 57, 58

Carol Ann Barnett Lammon, RN, PhD
Assistant Professor of Nursing Capstone College of Nursing University of Alabama Tuscaloosa, Alabama Chapter 17–21

Tracey Goldsmith, PharmD
Independent Legal and Healthcare Consultant Magnolia, Texas Chapters 33–37
Note: These chapters were reviewed by John Mohr, PharmD, Clinical Specialist, Infectious Diseases, Memorial Hermann Hospital, Houston, Texas

Sandra Smith Pennington, RN, PhD
Associate Professor of Nursing Berea College Berea, Kentucky Chapters 50, 52, 53, 54, 56

Constance J. Hirnle, RN, MN
Nursing Development Specialist Virginia Mason Medical Center Seattle, Washington and Lecturer, Biobehavioral Nursing and Health Systems University of Washington Seattle, Washington Chapter Opening Critical Thinking Scenarios, Nursing Notes: Apply Your Knowledge, How Can You Avoid This Medication Error?, and Ethical/Legal Dilemma

Frank Romanelli, PharmD, BCSP
Assistant Professor College of Pharmacy and College of Health Sciences University of Kentucky Lexington, Kentucky Chapters 39 and 41



NEW* Drugs at a Glance tables give students characteristics, and routes and dosage ranges in an easy-to-read format.





7 R2


t or kfas g or bjm brea O ecti er s ftve se 2 y. A with do il ST g AFTE aily, aR ce d startin once d e inUDYING THIS n o CHAPTE mg ximum 4 mg e1. dos k interR, THE 2 – – a s STUDEN eescus lly 1 eal. M dose 1 increa 2-wDi us s char T WILL um BE ABLE m initia ellit e to mac d, xim rolide an acteristics an TO: PO, t main tenanc reache s at 1- ls. Ma es M d spec tibacte e is firs Main bet les e lev2. ific uses g . r ria y ia y o m s . ls. il Co il h s da of stic less e of 2 f 2 mg gluco nce da nm or D re and epa 2–3 ri F c , te k s s o d o co o c 4. Disc common ntrast m pea rug mg a do ments n bloo 8 mg ; uss hara D ly h 8 ac C in us l o , rolides O ed antib a ut 1 for usin characteristic incre based d dose ulin, P 3. Ap e, 30 m wi : Or acteria abo pl s e , sy prin l drugs. th other o nce zolid, m g chloramphen s and clinical tion ciples of vals mend with in eal. le d Gla f ac indicatio etronida icol, cl using m sing client situat com ation ain m ta et o an a a re s d n ac io s va in in m ns. O rolides ncomyc zole, quinup indamycin, lin ns g on rst ame aily omb in select ristin/d in. eDru 5. Disc rati h In c h the fi mg d de N alfopris ed ene uss ily , wit y. wit ially 5 fast. /Tra tin, ose nd G dail g da vancom the roles of m eric eco init break 40 mg 2.5 m ingle d S , yc et Gen , in O ro in the tre nidazole P membr as ithitica Cr reas aryl) fore dose, rt w in e lu an at an l y b y t. m Th ou d il ent of ps oral inking s colitis on um ay sta Yo da (Am h; kfas g e a im Sc Sulf . .5 eu x m id u en m re 1 do a ar ario e an in y, M –5 1– epir ith b wio 2.5 lderl resistd Glim ately aily. dafe ilyct n contro an In e itially xim St g ap mg tm l nurse in ppro 20 ca.5 3 es y. hylococcus de who wi PO, akfast. se, de –, n, a h il ci pe aure ll y 1re g da bre m do dr ctio ug (MRSA) be providing mstan ally in long-te us u si itiall of a 10–16 2 t ; in e im . lo e 1 h x Becaus ce and rm it re Ma se PO dose, Ons ration 2–4 approp e MRS ng-term care nu rst b ca a als facilities, h firia A has be du rses wi ately tter ab tervm your Glyn ximum Reflect on: y wit k inte easure be roxim dail s to prev goal is to in en a significa th an update Ma ee aily app ase is about Factors crea nt mes - to 8-w mes d ary, ent spre on n t in tion th attipr 4 ree ad of th se knowledg problem over methicilline ti ecess t f ac 4 h. Gly r (onse given f om th a o re v W ot , l) t e abou hy e resi g nc ase is orga o e n is 2 o mva g th if st se le t the de the last m ) om ni 5 re cotr an Ons ration ts faste ), and forms o sm. g c 2 ce c yc 0 lu k in may velopm ; in Wha 60be th ially of 5 du e (G lsris an antib d glu thto , ac n 24 h other r t it a io e o id ent of d e e tic in s ks e s iz d lo e s. o m e re dr lb eun volve ugeof PO, main Glip sorb duratio s than tim m d har mo Wha choice ing inra se, ndiad h tuin e im ing wh ig io of max fe for MRS thre ect tp rona w 1 h; er dos n eig en s os co w mgvancomyc A. ll ro , Mic l pr1 to a atients n 1-h p lient 00 food t nts t in is us ac sma ride. tic rs te p Beta ) fi es to o C n ed r ra ia e . are e ce consiste u e up (fo nding hyd res e (D s Tab ifssary glyb ith th ned ranc ntly to e ses re p arbo urid re to limit treat M dep nd tole eed do dose). daily w crease of c food a at the Glyb nase P the spre RSA. a s d tion ct ad of M els g may n ximum e time ually in Gly iges ose an (GI) tra d a RSA an k ys d l rb 60 (the m mg thre al, gra d other y il a Dela en aca testina e d y resistan es OVERV dail itially 25 main m wh stroin m t organi ti rs o e a IEW sms. in ch d thre in g time hibit PO, e of ea . g an e mg e In 00 bit ssary ornin nts of sam idas 1 s m , e he o drugs de nece dose luc with creme p to a se) in th , o -G s y c a sc m il u te ribe th in ary, re duin this Alph e da se in xim t ydra eir antimic e (P s a n ic h s s e o o M su o tw ch mgte es and robial rb arb uses. So e d if nece on pati y r ar spectra, 500 ap fluids an as Aca of c rl e m d teroge eks incre wehe sene y char d may tion elde . dependin ;ac circumst e are used ofin In s 3 sticaily, ba itiall meals .ou te iges be bact g on dr –ri te in 2 ose ar an d vels m ys d ug eriostat some PO, en; g d s, san e effect very d u e le ning drugs ar ces. The m Dela tract cl ic or ba e0us 0m in im ive agai concentration ic ac co max /d e ar ev ed al g ro 0 e desc lu lid on ctericid 3 g GI m A in nst gram ly f d streptoc ribed in 500 es od toin spec an and dosa r develal, e loo m se s b u -positive infected tissu le oc a th if ct ic ci e d ed re mis ge ra fo , pneum xim are also an es. ut es allo inc w bng sk fo co eg ce m in t ri c oc atha lla r o re r of n se oc ef ne e e Glaa individu ctions; ci, and m cci, includin They ra fective ll ra ous le do n ma , nc e hig sis , po na to ta s g group ag al t os bl m ne ts , ai dr a n es, rout es. t staphy n m nst spec t) da, Neiss are c acido n. Thus functio atie ugs are listeaily es e lo lyse ie p s , co id s er lt cc of (G an iv ro u o l ti i. They dae e d d in the Dru bic orga ia, and Mycop Corynebacte acti r ad litol f lac rena two onc gs Mig Olde ment o fatal re ring of rium, Tr nisms su la e or Azithro mg 30 dos ech as Ba sma and agai mycin an op ntially ito M 15– one mon ed. ACROLID ns cteroide atypical d cl PO , in pote s and ES s and C t some mycobac arithromycin end aily e d s m d o re ) e lo m comb also are d e stridia. teria th efo pl use onc ex reco The macro hag e e g ac at (M p b in tiv id m o re cause M Ad e agains m a lides C) dise ay a luc in 0 uan 4–8 w (Zithro yc t th as ase hich , or n; ,m Big 1–3 fection c in (G reat include PO oses mfax suli tformin in th occurs m e. MAC diseas obacterium av e orm aily, al. mun d cl o in ), m eal; (Dyn um e is an ium es d a me im Metf ainly in ed erythr tsac omycin , e arithromyc c ab im h m od ef ic lin opportu ), l;ncy ie e usin (B people e tim if skip , az effe in eac E . Max m have si ay b su ea ith ssm iaxin), virus in nistic ni thre ro with ad ry ryth e ycin se h m m fore ssa g m a s a it ila s e ro ; o of m w an fe b r re ip va m n d ct antib . d diri e action. ycin, th nced hu it sk Inc ne or suli mth 120 if of min if neccas us ro e protot ion. man ee m ey are w acterial PO ec 30 yc alo54nylurea ts of in Th microbi ls. O 15– ls in do ype, is ea c idely di sp rmin o8 al resist meatra g d m it ath now us man re mha sulf es effe metfo stribut Om l. e developm h an ,1 ed le 1–2 g befo ec ily. a as en ith y wit r ce, numerou eak t il PO ed4in of to bo m g da d a me tabolized s drug in ss often beo Incre ne or w in; p w mdy e da ridne ) e er s m ic s tis to 6 in m e d te 1 ac twth lyliv ra ro alo 20 bu er .5 if a zon e, mately (Acto , e or ith e hin and excr lides. Erythrom ctions, and dos dose 20 Glita eak one onc %w g lly, PO 2 , wit a eted mai ycin is in; p h mg litaz ted is excr tion etted add menly 250 ly trea in: Initia n Piog f ac , 3–4h in 30 m ly 3–4 ) o to in urine. D n mg/ et o h us ndia ls, rm epending in bile; approx Ons duratio on, wit ximate (Ava 1.25 previo metfo h mea gs. ie on O ro n ti ; P it th ts s p c h e specifi dru plu daily w lly, Patien tazo of a tion ap te li ia a t c salt it ra ig e re . a In Ros Ons ; dura eals ulfonylu g twice of sep m h 1 g er s 500 m doses s ) m e th ix o / id 5 s rl mg 1.2 ; 2.5 iou litin (Sta or 5 ed prev in with Meg linide ons etform rmin; g in) exce m arati tfo tNate rand prep 0 mg g me e e (P le in and 25 500 m 0 mg m linid b g a a il Rep Ava buride de and and 50 gly lyburi uride g ce) mg mg glyb van rug* (Gluco or 5 in nD o in ti form bina metform m o C e/ urid Glyb R s oute and Dos R age



Macrol i Antibac des and Misc ellaneo terials us


dix pen e Ap *Se

A fo

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Chapter Objectives let students know what they’re going to learn in each and every chapter. Critical Thinking Scenarios at the beginning of each chapter help students prepare for using their knowledge in the real world. Prototype drugs are highlighted in the text for the first time.




Nursing Process material helps students think about Drug Therapy in terms of the nursing process.

How Can You Avoid This Medication Error? gives students examples of common mistakes, and helps them avoid them in the future.

There ar CHAPTE R 7 AN cosamin e no known ALGESIC cont –ANTIP e, YRETIC tation an but it should be raindications –ANTI-IN FLAMMA to the us d in child avoided TORY AN effects D RELA include ren, because ef during pregnanc e of gluTED DR GI upse fects are UGS y and la sea, cons • t cunknow Activity (eg, epig 113 tipation, n. In as rash. N A di to tri dv arrhea), lerance c pain, erse • Risk fo o intera he re dr la ar ow r te tb ctions w si been re • Risk fo Poisoning: Ace d to pain ith OTC ness, headache urn, nauported. r Injury taminop or prescr , and sk Glucosa re he lated to in renal in iption dr mine an adverse n overdose ugs have but are d chon drug effe • Defici sufficiency) m ent K cts (GI bl dosages ore often take droitin can ea eeding, common nowledge: Th n in co ch be us as listed erapeutic mbinatio ly used ed alon creased above. • drugs e, Deficien Use of and adve af this com n, with the sa t rse effe K J. Theo ter it was high no wledge: me bination cts of fever, an dosakis. ly praise C or grea d inflam rect use d in The As with mation of OTC Arthritis tly indrugs fo studies in studies of the Cure by Plannin r pain, in volving g/Goals glucosam dividual compo Americ The clie an ne ine and nt will: chondroi nts, many of th tion do College of Rhe no um e tin are fl • Experie aw they do t recommend th atology and th nc e Arthrit ed. The e use of not belie drug effe e relief of disc is th demonst Fo es ve undae supple reported omfort cts 193 rate • m GS si with m en Ex DRU gni research ts becaus perienc ANTISEIZURE disease inimal studies process. ficant relief of CHAPTER 11 e adverse • Inform e increased m sym ad These or with larg obility an health ca ganizatio ptoms or slow equately er grou re d re activity pr gu ure ps in ns ov cl seiz la g of peop in ientatta say long iders if ta rly of the s, so tole n and ime le reg m er ar ki • e bed cl e ng Se ph in needed. prescri aspirin or rance lf-admin ysicians 3 month When qu ical trials comply with the is suggest an s (gluco le te r the drug NSAID • Avoid estio ta 3 times samine y. A sing ov rap control. a da 500 mg king the supple ned by ation the • Use m eruse of the dr s safely y) ane. If d de versus combin toms ment fo and dication Error? sibl ugs easures n pos impr whe r Avoid This Me 3. Monotherapy y) is recommended ove (eg,ad-cide for themse chondroitin to prev dose, es How Can You whether 400 mg the less pa lves whe ent acci has notherap rgery in the pe (mo rapy rosu g ci othe neu dru th al for in mon , dental in ey wantdrug th ly in ch , • Experie icato your unit trolling seizures ildre g– to contin improved abili er their sympgestion e holds all med ly is admitted nce few effective in con effects, fewer dru ue. Ms. Hammer ty to w or over n night. The nurs er and le n er adverse drug alk) and h is usually take client is NPO after mid ss severe morning. She vantages of few medication, whic usually greater Interven attacks ly’s surgery is her antiseizure age, lower costs, and dos ti s, , Ms. Hammer of migra te on ion ning tions, including qua ract mor wers ade inte the sho in le 6 AM. In ine Implem first drug, her shower. Whi the adwith If le at midnight and . her ptab nce en t measu unacce complia ses decide to help N cau ed seizure. u or an s raliz rs re ure d gene delayed so you s as in a seiz inflamm to prev ces gP be rotrie merly experien fails to control ent or m ation: nt should ced ss ing, Ms. Ham • Treat inimize then another age sequen the di verse effects, pain, fe Aers recommend before ver, Most practition ssessm cumstan sease processe enher t apy monotherapy. as monot ce s nts (e s age e g, infect (e • thre g, Assess impaire activity ls of two to ion, arth tria fo Y tial . d , AP r apy po bl si ER ood supp ritis) or or positio s an OF TH bination therseverity, thergn ond be sec com d ci the sy , ring ca ly rni m side , us PRINCIPLES ng ptoms of la con duration, D for ano one AE • Treat ing pain, fever, or body alignm ck of physical pain, su (s ape ee Cha d utic theran factors th reac When substituting pain or inflam ch as lo top. ent) thou wed 6).h at cause cation, ed and•allo al mation ght to Assess dua vent seve as soon as po decreased lly or g should be add re dru gra fo ss is Therapeutic Go lie g ib re r dru ve the pa fever (try when le pain an ore the first[3 analgesi clients of all hermom 7.3 in d anxiet ; early treatm necessa C] not blood levels bef is c sϒ ent may nt of epilepsy for are Thi usua ontinued. vice eter readings other no drugs. Use dist y and allow th flus the main treatme llyor minimal adine hed fa co ama in dosage and disc nsidered e use of preabove 99 np Drug therapy is raction, ure activity with ce; zep e for carb reduced milder fever). relaxa apy, whe harmacologic .6ϒ ur is to control seiz oxcarbazepin t be individine m F ting mus apy stitu . ur sub H ther te l, ay ages. The goal ilar n in ot ch e output , dry sk niques al tion techniqu are sim accompa some• With ac appropriate. meet this goa D is drugsdr To AE the e le cts. in es, aus and ; at effe sing on ny g ; bec nd, an a ed g with dr d concen fever if . ive, a seco versa, ute mus verse dru tment with fect inef ug therth culoskel rapy•isA plicatio however, st clients, trea ssess fo bination therapy e person also trated etal inju When monothe ns com 30% of clients, ualized. In mo If to ca ed. r 20% n add in In be l. decrease ries (eg, flamm is dehy the Apply fo t this goa sess d, drug may edema, an nee bination ther at reas thir com a sp , to io pa es d eral ra n. tim in r sufficient to mee gen ins), co approx Log–l si , swel . In n may d pain or icia • Assist the clin druca Ds are required gns are fe interactions or ver, elical tend clients w imately 20 min ling, and inflam ld apditions is ineffective, two or more AE erness adverse effects, , med evatcon ith migra ure m ed whitediso ut ; system redness, heat, of seizan with more severe rder or ts. d weakn Assist cl ine to id es, then remov ation. seizure bloo client for type apy is associated the , and higher cos te es d nce entify an e. cell coun ic signs includ aggrava s. • W poor compliance an NSA ients to drink ions that plia Ds, ract com d ith AE e inte av and g t een ar dru oi Ds, (le betw 2 to 3 L ID regu thrit AE d “trigger ukocytos ss of is or othe ene ctiv la of effe he s.” rly fo fl is the lp r pain an uid daily ), . This s to m decrease regimen. r musculosk d lim therapy when ed • drugab ita of aspirin aintain good ki decreases gast client coneletal diso tio trol ns , con with the prescrib Ask ease dney fu ric irrita taking in ouseiz , fluids activd rders, as t usure incr nction. e of Ole, ity retion and n may cr he s tio an nde in se ys lp lec form exte fla d ss ta Se TC age to W m ls g m mp obility. ith pr in Dru m. 4. Dos analgesi re at For ory exa nce drugs an accurate • plia to preven the urinary tra event precipita long-term use com c, antip ntain mo abou venience, and Askdos ct. With tion s can mai d he or. Therefore, an yretic, t precip form CHA t al rb of PTER age al or 9 ANTIPSYCHOT lergic salic ofet or antian ted. In ure is a major fact urate ki •cting cy di uen ylate re IC DRUGS freq eCL actio ary supp reas g therapy is star 1. Type of seiz dney ston itation of urate tigout drugs, fl lease or long-a Asses dec forls nsIEN 153 hiand to Tpi leve gs ntial before dru TEA story le l CH ui onset crystals as dru es ora m tia ialm in en ING . part le lly seru ki rin Fl of ilab ent ts GU dn both ui w diagnosis is esse sist ava . pe IDE or d intake ey hen seru and form ds help con LINES NSAID Ds are ptAn dithe ic ul AE sord activity against of ce with m is st leve tip er ids at s. r of Ds Mo e, es ur . • sy di s. io liqu AE gin l ion , pecially uric acid ic acid le ch se n of oti ase, general le as ora c administrat With mig Dr ilab G include lamotri ug ava s im ve I s ar are ra ure bl po ls e in few seiz ee a being ex are high e, assess rtant inis; ding, or , and zonisamide. and generalized creted. and larg severity tablets or capsule ate, valproic acid Evaluat e amount s. ude an or da N solu maj pa be tte sition may ion tiracetam, topiram t useful for partial seizures incl s ipsy ng Dia or injectable ur cho e this Ant s ofsoc ticrn drug bec red are mos gn curr give gs conside osaus nobarbi• with n to ence be er dru es chro Intesch new • A nic men Drugs considered s. clients rvie gh the arbazepine, phe Cost should cu tal 5. hou oxc , illne izop w te Alt . ntin ss. hren an Pa nce ape Bec s, ia, gab d ob in ause of the•natu complia older a nt resp  These drug sea Inte than clie ence seizure d • ons in rv abs carbamazepine, or rate ible C re e rv For fact of tole hr adu re ie the s er ne. should be tape onic garding w an dise ase, and bett ein Pa , and tiagabi d ob ctiv about de- lt caregiver is needed red in dosage pam and chpart relief of ued grad leve whi to ls ng rv pro tal, phenytoin Costs, taki and discontinicul are generally effe quite expensive. of y;sy choice; clonaze . mpt a cliese they sho mpt nt e regarding uall - ar doses and to • is the drug of omuld the drug also rma man s. not be stopped abruptly pha Inte age mobili ther othe apy regimen, ed seizures, a com ethosuximide rvie r aspects agents, they are . w an lesale prices and as follows. effective. For mix d observ Medication Adm ty and activity s and ufacturers’ who th unt man e amo on e ry. valproate are also dr d inis dos e essa Gen pen trat ug regardin ion eral Considerati s. l as prescribed arch gs is usually nec wel • nge dru rese g as ons Ass s of cha as Se n g sa ist kup and atio lvin or prom lect drug fe,pt bin cies’ mar efthe gs are evo pharma fe  cies dru ng clie ct er Ask nt s amo iv y new to: abo ap use r var e for ut per propria  Take medicat us of of coststhe planned drug therap Guidelines erience with thei tely. other factors, may r, the following list ions in the e the desired resu y regi correct doses e and clinical exp approved for comeve times, to mai and at the corr and may be lts, when results can men, including Ds tent studies are don are ntain blood leve AEthe over time. How ect be expected, ative leng of these agents ls and beneficial  Avoid taking parisons among e- th of drug whose and gs are carb dru these medicat increases. Most therapy. effects.  r month allow com tice. Costs of olde AEDs in clients Mai er nta oth in h ions with anta an wit le ade is needed (eg, for cids. If an anta to $158), quate supply of med 05 adm in clinical prac led with a sing ($1 bination therapy ful trol regu de hea use con cid imi rtbu lar icat sux tely rn), ion to ensure it should be take inis adequa tration. Consist fore or 2 hours apy of and to $81), etho ), her 4 not ($5 $35 e n to mo 1 6 ent hou afte ess epin seizures are not for ($2 r bloo r the antipsycho ary to control sym ed maz bed leve nytoin crease absorpt pine is approv tic drug. Antacids thought ($2 to $5), phe gs are ptoms and prevent recu ls are necion of these drug er acu drug. Oxcarbaze new der drugs are also tedru phenobarbital illness and hos rring episodes ts of of  Lie down for s from the inte ; some of the othe pitalization. to $280). Cos  Do $289), stine. approximately to ($196 partial seizures allo valproate ($80 gine not w the client to y. an hour after ication, if dizz drive a car, ope or in as monotherap to to $354), lamotri perf receiving med 7 fact 39 g ines ($9 ($1 e idin orm s ntin pin and rate dec acti to be effective aze ape faintness occ machinery, or vities that requ arb gab be the  Take the med ur. ire alertness whe s can 05 to $315), oxcmedicat g effects may 4), ication at bed $35 8 toDro ion. ($8 n drowsy from types of seizure 2. Adverse dru time, if able, levetiracetam ($1 to $190), topiramate wsines ness aids slee so that drowsiD because most muscle p and is minimiz pre- s, slowed thinking, and imp e,atio abine ($99 coo gs. The use of sibl tiag rdin dru pos choosing an AE 8), of en  $35 ety ed aire n Wh Pra are duri vari 1). d ctice good ora especially like ng waking hou ely by a 2 weeks of begs ($100 to $20 l hygiene, incl ly during the fi rs. g dru drug ther be treated effectiv increased largely by choosin apy but tend to uding dental and zonisamide thorough and rst nce  Rep checkups, decrease with ort unusua and valproic acid frequent toothb chofor ourage complia l side time carbamazepine effects and all ce plans or, rushing, drin cognitive and psy and frequent scribers can enc ran cau nts’ insu king fluids, physical illnesse . se changesgin mouth rinsing. less sedation and dru ther covered by clie and phenytoin, drug s, Mou ive betal are cause they cause mon ther ens th arbi that apy dryn exp side nob  may be indicate ess is a com effect of the ent than phe choosing lessTry to prevent the client ous addrugs. Althoug d. serious, dry from taki motor impairm h it is usually uninsured clients, er potentially seri ications, includin mouth can lead not may cause oth and e availab ng unprescribed medly cause g s thos to mouth infe dental cavities ent girl although they AEDs reported le without pres apy regimens. thos ado ctions and e lesc prescribed for D . active st of the newer cription or AE another person, d than the  Minimize exp risk. Sexually an rate ncy uire tole verse effects. Mo req gna er able Pre bett who to prevent und 6. osure to sunligh al drug interactions e effects and are esirentially . Alcohol and t, wear protecti dbearing potentibe avoy clos and use sunscre ely becaus fewer adverse sleeping pills also cause pot ve clot women of chil ver ided bec en lotions. Sen ause they may should ough they may erse ed and monitored sitivity to sunligh hing, with some of cause excess ness and dec older drugs alth and milder adv the drugs and must be evaluat t occurs ive drowsireased awarene effects. Fewer may produce ness to of skin reaction ss of safety haz ling env wil iron a sunburn-typ s ’ nt serious adverse men clie . t. ards in the e increase a  atly Avo  gre id Kee exp can p osure to excess all physicians effects
informed abo being taken by ut all the med the client, to ications decrease risk able drug inte s of undesirractions. ive heat. Som ications may e of these med cause fever and heat prostration environmental with high temperatures. In hot weather keep the client or climates, indoors and use during the hou air conditioning rs of highest hea or fans t levels.

Client Teaching Guidelines gives students specific information they may need to educate patients. Nursing Notes: Apply Your Knowledge asks students a specific question about information from the chapter.

undergo extensiv e first-pass met abolism in the significant por liver so that a tion of a dose doe s not reach the culation and low systemic cirserum drug leve ls are produced. intramuscular In contrast, (IM) doses avo id first-pass met produce serum abolism and drug levels app roximately dou oral doses. Thu ble those of s, usual IM dos es are approxima oral doses. tely half the Initial drug ther apy for acute psy quire IM adminis chotic episode s may retration and hos pitalization; sym usually control led within 48 ptoms are to 72 hours, afte drugs can be giv r which oral en. When trea tment is initiate d with oral

drugs, divided daily doses are recommended. nance therapy, For mainteonce daily dos ing is usually pre gle bedtime dos ferred. A sine is effective for most clients. Thi increases com pliance with pre s scribed drug ther schedule better nighttime apy, allows sleep, and dec reases hypoten sion and day-

Nursing Notes:



Nursing Notes:

Apply Your Kn


You are assigne d to care for John Chou, hospitali and started on fl zed 2 weeks ago uphenazine hyd rochloride (Pro psychotic symptom lixin) to treat acut s. During your e assessment, John less, unable to sit appears reststill, and uncoord inated. He also tremor. How wou has a fine hand ld you interpre t these data?

Mr. Seager, 37 years of age and homeless, has been treated for schi diagnosed and zophrenia and alcohol abuse for He is admitted the last 15 year to the hospital for s. pneumonia. Wh room to adminis en you enter his ter his prescrib ed antipsychoti his antibiotic, c medication and he swears at you and tells you to because he has leave the room no plans to take that poison. Reflect on:

• Does Mr. Seager hav • Does his psychiat e the right to refuse to take his med ric history alte ication? r his rights? • Role play how you
the nurse in this would respond to Mr. Seager if you were situation.









ent and hepatic impairm ciated nts may develop ed antibiotic-asso t of critically ill clie s colitis (also call men nou elop bra dev mem pseudo at high risk for are agnts ive clie n rece colitis). These ause they ofte spectrum nous colitis bec ltiple or broadpseudomembra nrga therapy with mu roo tic mic bio el anti e gressiv normal bow gs that destroy ill clients d in critically antibacterial dru ole is often use for drug toxrisk at are isms. Metronidaz nts comycin ctions. These clie with mixed infe metabolites. Van ulation of active and achieves icity from accum ically ill clients ues well in crit ibitory coninh m imu penetrates tiss min ls well above the occi. Plasma therapeutic leve cci and enteroc Although most staphyloco centration for uld be monitored. renal function sho en orally to and giv ls is leve ycin g dru sion, vancom infu pristin IV alfo by en in/d Quinuprist usually giv branous colitis. treat pseudomem

because ically ill clients often used in crit occur in this and linezolid are ns commonly resistant pathoge infections with population.

NEW* Herbal and Dietary Supplement Content is highlighted so students are aware of how these alternative therapies can affect traditional medications.

gs may be Drugs at a Gla cellaneous dru nce: Drugs for nurse is rolides and mis Migraine of the home care Most of the mac Generic/Trade Name e setting. The role ; that is, the hom apy the Routes and Dos ther in ic n take age Ranges other antibiot adwith g as dru e Sero ut sam tonin agonist caregivers abo generally the s (Triptans) or nts l clie h ora ng Almotriptan (Axe d to teac For clients taki rt) nurse may nee PO 6.25 mg, s coliexpected effects. nou and repe bra n at after 2 h if mem atio istr min necesfor pseudo sary. Maximu the triptan (Amerge) m, 12.5 mg/24h or vancomycin tested inNara PO 1–2.5 mg metronidazole be collected and as a single dose ens may need to ; repeat in ins. 4 tox Riza h or if tript tis, stool specim nece ms an ssary. Maximum (Maxalt) ficile organis dif , 5 mg/d C. PO for 5 – ry 10 mg as a single laborato dos
Sumatriptan (Imitrex) e; repeat after 2 h if nece ssary. Maximu m dose, 30 mg/ d PO 25–100 mg as a single dos e. Maximum dose, 300 mg/d SC 6 mg as a single dose. Max imum, 12 mg/d Nasal spray 5, 10 or 20 mg by unit-dose spray device. Maximum, 40 mg/d PO 1.25–2.5 mg as a single dose; may repeat after 2 h if necessary. Maximum dose, 10 mg/d

Home Care




Macrolides an

d Miscellaneo

us Antibacter

Zolmitriptan (Zomig)


TIONS NURSING AC accurately g to manu1. Administer arations accordin ed hromycin prep er, at evenly spac a. Give oral eryt 6 to 8 oz of wat with , ions ruct inst facturers’ the clock. intervals, around

PO, sublingually, 1–2 mg at ons et of migraine, then 2 mg q30 min, if necessary, to a max imum of 6 mg/ 24 h or 10 mg/wk ty Inha emp lation, 0.36 mg on an (one inhalatio oral suspension n) at onset of migr ycin, give the ets without aine, repeat in b. With azithrom or 2 h after a meal. Give tabl Herbal and Die 5 min, if necessary, to re a maximum of with aluminum tary Supplem stomach, 1 h befo 6 inhalations/24 h Ergotamine tart oral azithromycin ents give not Do ns. ls. rate atio Adults: PO 2 tabl regard to mea In addition to the r’s recommend cids. and ly. ture anta caff rate ufac ing eine accu ets tain Man (Cafergot) con at onset of midrugs described well to measure the oral susgraine, then 1 ed or magnesiumand mix above, many her cine ets be ld s tabl are tablet q30 min used to relieve give regular bal medisuspensions shou lease cin, , if necAll d-re essa omy pain nde ithr ry, and exte up clar /or inflammatio to 6 tablets per of these (eg, com c. With . Give the attack or n. For most frey, marigold, 10 tablets/wk or without food on well before peppermint, prim usage is anecdo pension with Shake the suspensi Rectal suppos rose), such tal and unsupp XL) with food. itory 0.5–1 sup orte tablets (Biaxin d few by pos rucclin sup itory onset of migr ical studies. For plements, ther at tion, and inst dose. aine, repeat in e is some evid a stability in solu h after a meal. measuring the 1 h, if with few adverse necessary, up ence of effectiv ion has limited food or within 1 apeutic effects. to two suppos effects; these are eness ycin, give with The IV formulat to achieve ther itories per attack or rucdescribed belo Chondroitin sulf d. With dirithrom followed carefully tent and continuous infusions. five suppositori ufacturer’s inst w. tions must be es/wk ate (CS), a sup Children: PO 0.5 rmit , consult the man inte . Indiss ycin for ’ drug er aire hrom anim the diff – g plem ionn 1 eryt tablet initially, al cartilage or ent extracted ice for Leg e. For IV administerin Also, instructions then 0.5 tablet q30 manufactured ). treatment of cho ng, diluting, and 408 min, if necessar is the r 30–60 min SECTION 4 ycin treat arthritis, is synthetically and from DRUGS AFFECTING THE ENDOCRINE SYSTEM tions for dissolvi y, to a ly (eg, q6h ove maximum of thre Dihydroergotami IV erythrom . thought to dela used to y or intermittent e tablets ne it is rarely used y the breakdown tilage (by inhibit IM 1 mg at ons fuse continuousl mesylate (DH ease. Otherwise, of joint caring elastase, a et of migraine E 45) , may pro syn teol be repe ovial membranes ytic enzyme fou ated hourly, if d levels necessary, to bloo ), nd in tic to stim apeu ulate synthesis total of 3 mg a (by stimulating maintain ther Nursing Notes: Apply 12. For a diabetic n and of new cartilag rptio Your who reports using dietary and Knowle chondrocytes to dge IV 1 mg, client e herbal To increase abso phenicol: repeated, if nece produce teog lycan), and to pro supplem ls, q6h around f. With chloram ents, ssar analyze y, afterents in relation specific supplem 1 h; max mote the “shock- collagen and proor 2 h after mea re imu to m befo h dos with 1 e cart 2 mg. Do not ilage (by retainin absorbing” qua their potential exceed impact on blood (1) Give oral drug testinal (GI) upset occurs, give sugar control. 6 mg/wk. lity of g water). Answer: NPH gastroin

ty Ergot Preparat taken on an emp ions Some should be Ergotam n tartrate to meals. ntaiine without regard s help to mai regular interval (Ergomar) n; rptio abso aids Adequate water d levels. therapeutic bloo antacids decrease the suspension; s absorption of Food decrease ension ets and the susp absorption of tabl

can be taken stomach; some

metabolism of rizatriptan and zolmitriptan pro metabolites. Sub duces active cutaneous sum atriptan produc verse effects than es more adthe oral drugs, whi effects (eg, pain , paresthesias, nau ch have similar adverse sea ness). These dru gs are considered , dizziness, and drowsisafer than ergot Ergotamine tar alkaloids. trate (Ergomar) only in the trea is an ergot alka tment of migrain loid used e. Ergot prepar migraine by con ations relieve stricting blood vessels. Ergotam effective when ine is most given sublinguall y or by inhalat onset of headac ion at the he. When given orally, ergotam cally absorbed, ine is erratiand therapeutic effects may be to 30 minutes. delayed for 20 Ergotamine is contraindicated nancy and in the during pregpresence of sev ere hypertensio vascular disease, n, peripheral coronary artery disease, renal or ease, and severe hepatic disinfections. Ergotamine tar trate and caffein monly used anti e (Cafergot) is migraine prepar a comation. Caffeine increases the abs reportedly orption and vas oconstrictive effe gotamine. Dih ydroergotamine cts of ermesylate (DH semisynthetic derivative of erg E 45) is a otamine that is less effective than less toxic and the parent drug.

is an intermediate-acting insulin that Chondroitin is the clock. If usually a normal com peaks 8 to 12 hours after administration. ponent of join which contains Hypoglycemia is most food. 5% dextrose t cartilage, water (65 to 80% 50–100 mL of likely to occur before meals. The morning ), collagen, pro and chondrocy ramphenicol in NPH is most likely to SELECTED REFERENCES teoglycans, tes that produc . (2) Mix IV chlo min cause 30 hypoglyce – mia before dinner and the evening NPH e new collagen se over 15 cans. CS was fi spe is ci likely fi call and proteoglyy rst in water and infu for use n the to cause hypoglycemia after d as a dietary sup trea American tme Diabetes eal irritatio midnight, Associatio nt the hag so of n. diabetics (2002). ies mod ken Insulin esop need plem sug to administra id The thic eat erat an : tion. avo ges y e ent may Diabetes are or severe migrain To ted that it wou ycin because studed sele evening snack. Care, 25 (Suppl. 1, Clinical Practice drug stability and callrate g. With clindam ld promote hea es. 2002, sero Recommendations toni ly. ctive dam n 5-HT1 receptor s of water. January), cau pou aged by inflamm not required for r accu ling of cartilag they act on aS112 with a full glas –S115. agonists beRefrigeration is sure and se ation or injury. speci e fic sub . (1) Give capsules on the client’s it difficult to mea The daily dose crease sero of sero J. B. (1999).type tonin rece tuted oral solution Overview toninBuse, weight: under solution, making of current is based therapeutic ptor to (5-hydr formation options igerate reconsti in- in type 2 diabetes. oxy abscess 120 tryp and 200 n, tam lbs, Diabetes The ratio lbs, ine 800 (2) Do not refr Care, y indu or C65 1200 mg CS; ove 22(Suppl. 3), relieve migrain mg CS; 120 to 5-H –T) C69. in the brain. decrease pain, To e ) r by 200 ed . con tinu lbs, DerMarder sites stric ally taken with te Can You Avoid This Medication How (con osian, A. (Ed.) 1600 mg CS. CS ting(2001). of their vasoco bloodThe review of natural products. St. ves Error? deeply, and rota food, in two to sels. Bec Louis: is usunstrictive Compariso ause cular injections properties four divided dos ns. ction. Proponents of CS indicated in clie Facts and , the drugs are (3) Give intramus es. in a single inje Answer: Metformin nts wit cite clinical trial Drug contrafacts comparison h and e than 600 mg a hist (Glucophage) should be discontinued s. (Updated monthly). effeand ory of ang s that indicate ben St Louis: Facts cts.Comcard a few For example, ialdays Do not give mor ina pectori infarction, parisons. before any efi
diagnostic procedure involving a contrast s, myocial one study cited or uncontrolled compared CS with medium toons vary in dehypertension. The Fetrow, C. W. & Avila, crease the chance of lactic acidosis, diclofenac sodium by Fetrow and Avila R. (1999). Professional dru a potentially lethal side effect. et of action, with ’s handbook gs of complemen subcutaJ. with , an NSAID, in the most rapidly tary & alternative osteoart neous sum The incidence of lactic acidosis increases hritis of the kne 146 clients atriptan Springhous e, PA: when renal insufficiency and starting to medicines. Springhous acti e Corporation. ng e. The NSA auth is present. Urinary tract infections can Fleming, reli with ors ID D. R. eve migg (1999). Challengin concluded that relieved pain fast in 10 minutes. Mo traditional contribute to renal damage. rain insulin e headac the er but the effects st clie he injection Documenting in Mrs. Watson’s chart nts get American up topractices. Journal ofreli with Nursing, 3 months after of CS lasted long 99 (2),1 that she has taken ef wit 72 all –74. of the ora hin her mettreatment. Propon to 2 hours l drugs. er, formin is good but this is not enough Guven, S., Kuenzi, The dru J. gs A., are & Mat of CS In fin, G. (2002). Diabetes because the physician ents also tout the liver bymay inC. com met monoaminPorth M. parison with abolized in the mellitus. overlook reading it in the chart. The physician safety e oxi(Ed.), the dase Pathophysi adv ology: Concepts erse or cytochr should be notified bemai of altered effe health n states, adv cts of NSAIDs. 6therse ed., effects ome P450 enzym cause it would be prudent to reschedule pp. 930–952. Philadelphia: are reportedly The Lippincott Williamses; Mrs. Watson’s IVP. & Wilkins. addition, there minor stomach Guyton, A. C. & Hall, J. E. (2000). Textbook is ups a theo et. retical risk of blee In of medical physiology, 10th ed. ding because of Philadelphia: W. B. Saunders. the Halter, J. B. (2000). Approach to the elderly patient with diabetes. In H. D. Humes (Ed.), Kelley’s Textbook Review and Application Exercises of internal medicine, 4th ed., pp. 3032–3037. Philadelphia: Lippincott Williams & Wilkins. Hoffman, R. P. (2001). Eating disorders in adolescents with type 1 diabetes. 1. What is the function of insulin in normal Postgraduate Medicine, 109(4), 67–69, 73–74. cellular metabHu, F. B., Manson, J. E., Stampfer, M. olism? J., et al. (2001). Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. New England Journal of 2. What are the effects of insulin, cortisol, Medicine, 345(11), 790–797. epinephrine, glucagon, and growth hormone on blood Inzucchi, S. E. (2002). Oral antihyperg glucose levels? lycemic therapy for type 2 diabetes. Journal of the American Medical Association 3. What are the major differences between , 287(3), 360–372. type 1 and type Kudolo, GB. (2001). The effect of 3-month 2 diabetes? ingestion of ginkgo biloba extract (EGb761) on pancreatic beta-cell function in response to glucose 4. What is the rationale for maintaining loading in individuals with non-insulin-dependent diabetes mellitus. near-normal blood Journal of Clinical Pharmacology, 41(6), glucose levels? What is the major risk? 600–611. Ludwig, D. S. & Ebbeling, C. B. (2001). Type 2 diabetes mellitus in chil5. At what blood glucose range is brain dren. Journal of the American Medical damage most likely Association, 286(12), 1427–1430. to occur? Massey, P. B. (2002). Dietary supplement s. Medical Clinics of North America, 86(1), 127–147. 6. Compare regular, NPH, and Lente insulins in terms of Mautz, H. (2001). Undiagnosed diabetes common among Mexican-Americans. onset, peak, and duration of action. Diabetes Care, 24(7), 1204–1209. 7. Describe major characteristics and Rocchini, A. P. (2002). Childhood obesity and a diabetes uses of insulin epidemic (Editorial). New England Journal of Medicine, 346 analogs. (11), 854–855. Setter, S. M., White, J. R., Jr., & Campbell, R. K. (2000). Diabetes. In E. T. 8. In a diabetic client with typical signs and symptoms, disHerfindal & D. R. Gourley (Eds.), Textbook of therapeutic s: Drug and tinguish between manifestations of hypergly disease management, 7th ed., pp. 377– cemia and 406. hypoglycemia. Silverstein, J. H. & Rosenbloom, A. L. (2000). New developments in type 1 (insulin-dependent) diabetes. Clinical 9. Contrast the five types of oral hypoglyc Pediatrics, 39, 257–266. emic agents in Sinha, R., Fisch, G., Teague, B., et al. (2002). Prevalence of impaired gluterms of mechanisms of action, indicatio cose tolerance among children and adolescents ns for use, conwith marked obesity. New traindications to use, and adverse effects. England Journal of Medicine, 346(11), 802–810. Skyler, J. S. (2000). Approach to hyperglyce 10. For an adult client newly diagnose mia in the patient with diad with type 2 diabetes mellitus. In H. D. Humes (Ed.), Kelley betes, outline interventions to assist the ’s Textbook of internal medclient in learnicine, 4th ed., pp. 2635–2648. Philadelph ia: Lippincott Williams & ing self-care. Wilkins. Thompson, W. G. (2001). Early recognition and treatment of glucose abnormalities to prevent type 2 diabetes mellitus and coronary heart disease. Mayo Clinic Proceedings, 76, 1137–1143.

Home Care content is highlighted in the text. Nursing Actions give students specific instructions on administration of drugs, with rationales for each step.

11. Prepare a teaching plan for a client starting insulin therapy and for a client starting an oral hypoglyc emic drug.

Nursing Notes and How Can You Avoid This Medication Error? answers are provided at the end of the chapter so students can think on their own, and compare their answers to the ones within the text. Review and Application Exercises gives students the opportunity to review what they just learned.

RN. New York Deanna L. RN. Pennsylvania viii . RNC. BSN Nursing Instructor Southwest Virginia Community College Grundy. CNS Associate Professor Columbus State Community College Columbus. Indiana Judy M. RN. RN. RNC. Reising. MSN Associate Professor of Nursing Pennsylvania College of Technology Williamsport. RN. RN. Mississippi Dorothy Mathers. MS Associate Professor of Nursing Onondaga Community College Syracuse. Wisconsin Christine Hobbs. MS. Virginia Denise R. MEd. Missouri Peggy Przybycien. BScN. Ohio Mary Jo Kirkpatrick. RN. MSN Nursing Instructor Northeast Wisconsin Technical College Green Bay. MEd Professor Humber College of Applied Arts and Technology Etobicoke.Reviewers Sarah P. MSN Assistant Professor of Nursing Truman State University Nursing Program Kirksville. Ontario Canada Assistant Professor Indiana University School of Nursing Bloomington. York. Delaware. BSN. MSN Director. CS. Associate of Science in Nursing Mississippi University for Women Columbus. PhD Mary Elliott. Truttmann. BSN.

1 Introduction to Drug Therapy .

Have you ever wondered why it’s usually okay to give children Tylenol but not aspirin? Why a lot of middle-aged and older people take an aspirin a day? Why people with high blood pressure. ᮣ Review your course syllabus and pharmacology text. Differentiate between generic and trade names of drugs. Develop personal techniques for learning about drugs and using drug knowledge in client care. Select authoritative sources of drug information. and disease processes. Analyze the potential impact of drug costs on drug therapy regimens. Develop a learning plan (eg. Much of what you learn will apply to your personal and family life as well as your professional life as a nurse. You anticipate that pharmacology will be challenging. Perhaps you’ve given medicines to your children. Define a prototypical drug. a skills laboratory. Discuss major drug laws and standards. This quarter you will be taking a basic nursing theory course. 2. 6. diagnose. Critical Thinking Scenario This is your first semester of clinical nursing. 9. Discuss nursing responsibilities in handling controlled substances correctly. and pharmacology. Bon voyage!! OVERVIEW Pharmacology is the study of drugs (chemicals) that alter functions of living organisms. relief of symptoms can greatly improve quality of life and ability to function in activities of daily living. Differentiate between pharmacology and drug therapy. heart failure. 7. Reflect on: ᮣ List successful strategies you have used in the past to learn difficult material. 4. readings. The purpose of 2 Y this book is to help you learn about medicines and the why. or others. THE STUDENT WILL BE ABLE TO: 1. and where they are used in daily life. student study groups) and develop a plan to use them. Differentiate the main categories of controlled substances in relation to therapeutic use and potential for abuse. learning center. study times for major tests) and enter this plan into your calendar. . assignments. A MESSAGE TO STUDENTS ou’ve probably been taking medicines and seeing other people take medicines most of your life. how. Discuss the role of the Food and Drug Administration. Drugs given for therapeutic purposes are usually called medications.chapter 1 Introduction to Pharmacology Objectives AFTER STUDYING THIS CHAPTER. or diabetes take ACE inhibitors and what ACE inhibitors are? When an antibiotic should NOT be prescribed for an infection? You are embarking on an exciting journey of discovery as you begin or continue your study of pharmacology. 3. grandparents. when. symptoms. or treat signs. peer tutors. also called pharmacotherapy. 10. Drug therapy. 8. parents. When prevention or cure is not a reasonable goal. you want to develop a strong foundation in pharmacology. is the use of drugs to prevent. 5. what. To increase your clinical knowledge and ensure that you will be a safe practitioner. Reflect on which strategies might be helpful this semester. ᮣ Assess support for your learning at your school (eg.

which may require years of work and millions of dollars. drugs were mainly derived from plants (eg. Semisynthetic drugs (eg. which are often the first drug of a particular group to be developed. The trade name is designated and patented by the manufacturer. Drug classifications and prototypes are quite stable. For example. trade names are capitalized and generic names are lowercase unless in a list or at the beginning of a sentence. antihypertensives. penicillin is the prototype of antibacterial drugs. To meet this goal. Each hybrid molecule produces a genetically identical molecule. some groups lack a universally accepted prototype and some prototypes are replaced over time by newer. called a clone. Cloning makes it possible to identify the DNA sequence in a gene and produce the protein product encoded by a gene. However. a narcotic or opioid analgesic. act mainly at the site of application. For example. Trimox) and several of which use only the generic name. Generic drugs are required to be therapeutically equivalent and are much less expensive than trade name drugs. Now. DRUG CLASSIFICATIONS AND PROTOTYPES Drugs are classified according to their effects on particular body systems. Drugs with local effects. The generic name often indicates the drug group (eg. Chemists. SOURCES OF DRUGS Where do medications come from? Historically. Prototypes. amoxicillin is manufactured by several pharmaceutical companies. insulin). Drugs may be prescribed and dispensed by generic or trade name. The names of therapeutic classifications usually reflect the conditions for which the drugs are used (eg. antidiabetic drugs). animals (eg. and an incentive for developing other drugs. Many commonly used drugs fit into multiple groups because they have wide-ranging effects on the human body. This is seen as a return on the company’s investment in developing a drug. Amoxil. drugs with generic names ending in “cillin” are penicillins). Such techniques and other technologic advances have enabled the production of new drugs as well as synthetic versions of many drugs originally derived from plants and animals. many antibiotics) are naturally occurring substances that have been chemically modified. more consistent in their effects. This process involves manipulating deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) and recombining genes into hybrid molecules that can be inserted into living organisms (Escherichia coli bacteria are often used) and repeatedly reproduced. For example. and their chemical characteristics. including insulin and several other body proteins. some of which assign a specific trade name (eg. adding. Prozac was approved in 1987 and went off patent in 2001. more commonly used drugs. morphine). Many drugs are given for their long-term effects. in acute problems such as pain or infection) or long-term effects (eg. similar drugs are compared. such as citalopram (Celexa). for example. their therapeutic uses. Drugs may also be given for relatively immediate effects (eg. and most new drugs can be assigned to a group and compared with an established prototype. For example. groups reflect their chemical characteristics rather than therapeutic uses (eg. morphine can be classified as a central nervous system depressant. are usually the standards with which newer. benzodiazepines). adrenergics. In many instances. to relieve signs and symptoms of chronic disorders). fluvoxamine (Luvox). but the two most commonly used are the generic name and the trade name (also called the brand or proprietary name). for new drugs that are popular and widely used. deleting. and less likely to produce allergic reactions. Synthetic drugs are more standardized in their chemical characteristics. and minerals (eg. morphine is the prototype of opioid analgesics. the names of many drug . the goal of drug therapy is to lessen disease processes rather than cure them. can often create a useful new drug by altering the chemical structure of an existing drug (eg. and eventually eliminated from the body. antidepressants. circulated through the bloodstream to their sites of action in various body tissues. amoxicillin) is related to the chemical or official name and is independent of the manufacturer. The generic name (eg. meaning that any pharmaceutical company could then manufacture and market the generic formulation of fluoxetine. However. during which it can be marketed only by the pharmaceutical manufacturer that developed it. drugs may be given for local or systemic effects. In drug literature. the marketing of fluoxetine (Prozac) led to the introduction of similar drugs from different companies. and as an opiate (derived from opium). Other pharmaceutical companies cannot manufacture and market the drug. DRUG MARKETING A new drug is protected by patent for 14 years. antiadrenergics. Most drugs are given for their systemic effects. paroxetine (Paxil). Cloning also allows production of adequate amounts of the drug for therapeutic or research purposes. Biotechnology is also an important source of drugs. such as sunscreen lotions and local anesthetics. DRUG NAMES Individual drugs may have several different names. However. other companies often produce similar drugs. most drugs are synthetic chemical compounds manufactured in laboratories. Individual drugs that represent groups of drugs are called prototypes. iron).CHAPTER 1 INTRODUCTION TO PHARMACOLOGY 3 Medications may be given for various reasons. or altering a side-chain). with different generic and trade names. and sertraline (Zoloft). Those with systemic effects are taken into the body.

How did the resources you used differ in the organization and depth of information provided about drugs? DRUG APPROVAL PROCESSES The FDA is responsible for assuring that new drugs are safe and effective before approving the drugs and allowing them to be marketed. Prescriptions for Schedule II drugs cannot be refilled. and labeling of drugs. hallucinogens. keep accurate records of all transactions. It also confers official status on drugs listed in The United States Pharmacopeia. from managed care organizations) to prescribe less costly drugs. and the Federal Trade Commission can suppress misleading advertisements of nonprescription drugs. including those of purchasing. Canadian Drug Laws and Standards Canada and its provinces have laws and standards that parallel those of the United States. laboratory and other tests used to monitor client responses. Title II of this law. distribution. and reporting discrepancies to the proper authorities. Physicians are assigned a number by the DEA and must include the number on all prescriptions they write for a controlled substance. and Cosmetic Act of 1938 was especially important because this law and its amendments regulate the manufacture. Their main provisions are summarized in Table 1–1. maintaining an accurate inventory. administering them only to people for whom they are prescribed. dentist. and Cosmetic Act. recording each dose given on agency narcotic sheets and on the client’s medication administration record. The FDA reviews research studies (usually conducted or sponsored by a pharmaceutical company) about proposed new drugs. is labeled C–II). morphine. look up the following drugs: meperidine and diazepam. there is considerable pressure on prescribers (eg. Nursing Notes: Apply Your Knowledge Using this text and a drug handbook. and losses from expiration. Another important law. Their main goal is to protect the public by ensuring that drugs marketed for therapeutic purposes. the Comprehensive Drug Abuse Prevention and Control Act. salaries of pharmacists. reflect on why each drug was placed in the assigned category. American consumers have two routes of access to therapeutic drugs. or the Physicians’ Desk Reference (PDR). Costs are increasingly being considered a major factor in choosing medications. In addition to federal laws. and research projects that compare costs have greatly increased in recent years. a Schedule II drug. Drug. advertising. particularly those related to controlled substances (see Appendix D). American Drug Laws and Standards Current drug laws and standards have evolved over many years. was passed in 1970. stimulants. Nurses are responsible for storing controlled substances in locked containers. depressants. The Drug Enforcement Administration (DEA) is charged with enforcing the Controlled Substances Act. or nurse practitioner. Indicate the controlled substance category for each drug. a new prescription is required. Drug. state laws also regulate the sale and distribution of controlled drugs. storage. The names of these drugs may be fol- lowed by the letters USP. In addition. administration (eg. Acquiring and using prescription drugs for nontherapeutic purposes. The goal of most studies is to define drug therapy regimens that provide the desired benefits at the least cost. and provide for secure storage. called the Controlled Substances Act. if so. the organization does not test the drugs. PRESCRIPTION AND NONPRESCRIPTION DRUGS Legally. From the information you obtained in researching the drug. salaries of nurses. The Food. These laws may be more stringent than federal laws. regulates the manufacture and distribution of narcotics.4 SECTION 1 INTRODUCTION TO DRUG THERAPY PHARMACOECONOMICS Pharmacoeconomics involves the costs of drug therapy. are safe and effective. For drugs or regimens of similar efficacy and toxicity. whether prescription or OTC. Individuals and companies legally empowered to handle controlled substances must be registered with the DEA. the stricter laws usually apply. such as a physician. the Public Health Service regulates vaccines and other biologic products. costs of supplies). by persons who are not authorized to have the drugs or for whom they are not prescribed. Before passage of the Food. Length of illness or hospitalization is also considered. and anabolic steroids. dispensing (eg. is illegal. many drugs were marketed without confirmation of safety or . The DurhamHumphrey Amendment designated drugs that must be prescribed by a physician and dispensed by a pharmacist. The Food and Drug Administration (FDA) is charged with enforcing the law. pharmacy technicians). These drugs are categorized according to therapeutic usefulness and potential for abuse (Box 1–1) and labeled as controlled substances (eg. One route is by prescription or order from a licensed health care provider. Official drugs must meet standards of purity and strength as determined by chemical analysis or animal response to specified doses (bioassay). Both of these routes are regulated by various drug laws. The other route is by over-the-counter (OTC) purchase of drugs that do not require a prescription.

drugs considered unsafe for use except under supervision by a health care provider. and Cosmetic Act 1945 1952 Amendment Durham-Humphrey Amendment 1962 Kefauver-Harris Amendment 1970 1978 1983 1987 1992 Comprehensive Drug Abuse Prevention and Control Act. Food and Drug Administration. barbiturates not listed in other schedules). with each new drug application. Included are antidiarrheal drugs. marijuana. BOX 1–1 CATEGORIES OF CONTROLLED SUBSTANCES drogens and anabolic steroids. methamphetamine. peyote. Schedule III Drugs with less potential for abuse than those in Schedules I and II. chloral hydrate). temazepam). secobarbital). They may be dispensed by the pharmacist without a physician’s prescription but with some restrictions regarding amount. but abuse may lead to psychological or physical dependence: an- . Drug. codeine. phentermine). and use of opium. benzphetamine). and other drugs that the act defined as narcotics • Required proof of safety from the manufacturer before a new drug could be marketed • Authorized factory inspections • Established penalties for fraudulent claims and misleading labels Required governmental certification of biologic products. and barbiturate sedative-hypnotics (amobarbital. mescaline. marijuana. cocaine. mazindol. and drugs limited to prescription use under a manufacturer’s new drug application) • Required a manufacturer to provide evidence (from well-controlled research studies) that a drug was effective for claims and conditions identified in the product’s labeling • Gave the federal government the authority to standardize drug names • Regulated distribution of narcotics and other drugs of abuse • Categorized these drugs according to therapeutic usefulness and potential for abuse Pure Food and Drug Act Sherley Amendment Harrison Narcotic Act Food. record keeping. Schedule I Drugs that are not approved for medical use and have high abuse potentials: heroin. codeine. oxycodone.CHAPTER 1 INTRODUCTION TO PHARMACOLOGY 5 TABLE 1–1 Year 1906 1912 1914 1938 Name American Drug Laws and Amendments Main Provision(s) Established official standards and requirements for accurate labeling of drug products Prohibited fraudulent claims of drug effectiveness Restricted the importation. and other safeguards. and mixtures containing small amounts of controlled substances (eg. oxymorphone). Title II. lorazepam. lysergic acid diethylamide (LSD). tetrahydrocannabinol. by hiring more staff) • Specified a review time of 12 months for standard drugs and 6 months for priority drugs • Updated regulation of biologic products • Increased client access to experimental drugs and medical devices • Accelerated review of important new drugs • Allowed drug companies to disseminate information about off-label (non–FDA-approved) uses and costs of drugs • Extended user fees FDA. pentobarbital. methadone. cocaine. to shorten the review time (eg. methylphenidate). Schedule V Products containing moderate amounts of controlled substances. hydromorphone. phenobarbital. Schedule IV Drugs with some potential for abuse: benzodiazepines (eg. sale. such as diphenoxylate and atropine (Lomotil). some CNS stimulants (eg. diazepam. such as insulin and antibiotics Designated drugs that must be prescribed by a physician and dispensed by a pharmacist (eg. Schedule II Drugs that are used medically and have high abuse potentials: opioid analgesics (eg. Controlled Substances Act Drug Regulation Reform Act Orphan Drug Act Prescription Drug User Fee Act 1997 FDA Modernization Act • Established guidelines for research studies and data to be submitted to the FDA by manufacturers • Shortened the time required to develop and market new drugs • Decreased taxes and competition for manufacturers who would produce drugs to treat selected serious disorders affecting relatively few people • Established new regulations designed to speed up the approval process for high-priority medications • Allowed the FDA to collect user fees from pharmaceutical companies. meperidine. other sedative-hypnotics (eg. manufacture. and some prescription appetite suppressants (eg. morphine. controlled substances. central nervous system (CNS) stimulants (eg.

Motrin is the common trade name and dosage may be 400. Can consumers accurately self-diagnose the condition for which a drug is indicated? 2. Most clinical trials use a randomized. usually because of adverse effects that become evident only when the drug is used in a large. fever. excretion. allows the drug to be marketed for general use. some drugs are marketed but later withdrawn. indications for use may be different. a few doses are given to a few subjects with the disease or symptom for which the drug is being studied. Many potential drugs are discarded and never marketed. especially for drugs used to treat acquired immunodeficiency syndrome. With OTC drugs. with or without consultation with a health care provider. and dysmenorrhea. Individual patients are not identified in these databases. Other research methods include control studies. absorption. a few doses are given to a few healthy volunteers to determine safe dosages. The FDA has increased efforts to monitor marketed drugs more closely in recent years. In Phase I. In 1992. In Phase II. and subject matching. With prescription ibuprofen. 600. new drugs are categorized according to their review priority and therapeutic potential. each subject receives the experimental drug during half the study and a placebo during the other half. if any. and administration of the test drug to one group and a control substance to another group. and determines a need for the drug. and may require additional clinical trials to determine safety and effectiveness of OTC use. and recommended doses are usually lower for the OTC formulation. with neither subjects nor researchers knowing who receives which formulation. Several drugs have been withdrawn in recent years. verse effects. With prescription drugs. using information on the product label. and requires manufacturers to continue monitoring the drug’s effects. Phase III studies help to determine whether the potential benefits of the drug outweigh the risks. the drug is given to a larger and more representative group of subjects. In Phase III. One such effort involves contracts with some commercial companies that provide access to databases containing information on the actual use of prescription drugs in adults and children. The FDA also approves drugs for OTC availability. Advil) in 200-mg tablets and used for pain. procedures were changed to accelerate the approval process. the recommended dose is usually 200 to 400 mg three or four times daily. Since then. partly or mainly because of the increased postmarketing surveillance. interpret warnings and contraindications and determine whether they apply. especially for their adThe FDA approves many new drugs annually. which combinations of medications are being prescribed to patients. including the transfer of drugs from prescription to OTC status. or 800 mg three or four times daily. Examples of information include how long nonhospitalized patients stay on prescribed medications. for OTC ibuprofen. In Phase IV. Most newly approved drugs are “1S” prescription drugs. In crossover studies. controlled experimental design that involves selection of subjects according to established criteria. Testing usually proceeds if there is evidence of safety and effectiveness but may be stopped at any time for inadequate effectiveness or excessive toxicity. in which clients are paired with others of similar characteristics. half the subjects receive the new drug and half receive a placebo. random assignment of subjects to experimental groups. metabolism. which is available under its generic and several trade names (eg. Questions to be answered include the following: 1. the client must make these decisions. and toxicity. Can consumers read and understand the label well enough to determine the dosage. placebo-controlled designs. In double-blind. The drug then undergoes clinical trials in humans. however. proponents claim that the faster review process helps clients with serious diseases to gain effective treatment more quickly. subjects serve as their own controls. the FDA evaluates the data from the first three phases for drug safety and effectiveness. and the use of prescription drugs in hospitalized children. Food and Drug Administration Approval Testing and Clinical Trials The testing process begins with animal studies to determine potential uses and effects. The next step involves FDA review of the data obtained in the animal studies. and shifts primary responsibility for safe and effective drug therapy from health care professionals to consumers. The drugs are carefully evaluated at each step. “1P” status indicates a new drug reviewed on a priority basis and with some therapeutic advantages over similar drugs already available. often with the help of laboratory and other diagnostic tests. Some adverse drug effects may become evident during the postmarketing phase as the drug is more widely used. “1S” status indicates standard review and drugs with few. Critics contend that changes enacted to streamline the approval process have allowed unsafe drugs to be marketed. newly developed drugs have been extensively tested before being marketed for general use. For example. and responses are compared with those of healthy subjects. Since 1962. the new drug is similar to one already available). routes of administration. FDA approval of a drug for OTC availability involves evaluation of evidence that the consumer can use the drug safely. and recognize drugs already being taken that might interact adversely with the drug being considered? . a health care professional diagnoses the condition. For drugs taken orally. Numerous drugs have been transferred from prescription to OTC status in recent years and the trend is likely to continue. in which some clients receive a known drug rather than a placebo. diverse population. therapeutic advantages (ie.6 SECTION 1 INTRODUCTION TO DRUG THERAPY efficacy.

Its abuse potential is high and it is therefore given a Schedule II classification. The PDR. 7. pharmaceutical companies’ sales and profits increase and insurance companies’ costs decrease. especially for dosage ranges. Concentrate on therapeutic classifications and their prototypes. conditions in which the drug is contraindicated or must be used cautiously.rxmed. Use the reference freely whenever you encounter an unfamiliar drug or when a question arises about a familiar one. Relating the unknown to the known aids learning and retention of knowledge. and trade names of drugs encountered in clinical practice settings directly into your pharmacology textbook. it was estimated that Americans spent more than $19 billion on OTC drugs. It is published annually. These include the main indications for use. and developing adverse drug reactions and interactions. It provides the reader with drug inserts from the manufacturer and color photographs of many medications. a textbook is usually the best source of information because it describes groups of drugs in relation to therapeutic uses. It is the best resource to use when you are first learning about drugs. A widely available but less authoritative source is the Physicians’ Desk Reference (PDR). Diazepam (Valium) is an antianxiety agent that has some potential for abuse. 6. Drug reference books are most helpful in relation to individual drugs. 3. “What if I have a client who is receiving this drug? What must I do to safely administer the drug? For what must I assess the client before giving the drug and for what must I observe the client after drug administration? What if my client is an elderly person or a child?” Nursing Notes: Apply Your Knowledge Answer: Meperidine (Demerol) is an opioid analgesic that is used to manage severe pain. is a compilation of manufacturers’ package inserts for selected drugs. Disadvantages include inaccurate self-diagnoses and potential risks of choosing a wrong or contraindicated drug. For the beginning student of pharmacology. This allows you to predict therapeutic effects and to predict. Much information is provided. SOURCES OF DRUG INFORMATION There are many sources of drug data. The PDR is available in many health care facilities. published yearly. and possibly increased efforts by consumers to learn about their symptoms/conditions and recommended treatments. so it is listed as a Schedule IV drug. 6). drug reference books. 2. The mental processing required for these activities helps in both initial learning and later retention of knowledge. and Internet sites. published annually) and pharmacologic. For the year 2000. and related nursing care needs. fewer visits to a health care provider. Compare a newly encountered drug with a prototype when possible. . which can make it difficult for a beginning student to use effectively. journal articles. The latter is published by the Facts and Comparisons division of Lippincott Williams & Wilkins and updated monthly (looseleaf edition) or annually (hardbound edition). common and potentially serious adverse effects.CHAPTER 1 INTRODUCTION TO PHARMACOLOGY 7 3. Numerous drug handbooks (eg. write notes. medical. STRATEGIES FOR STUDYING PHARMACOLOGY 1. Journal articles often present information about drug therapy for clients with specific disease processes and may thereby facilitate application of drug knowledge in clinical practice. Try to understand how the drug acts in the body. possibly earlier resumption of usual activities of daily living. Helpful Internet sites include the Food and Drug Administration (http:// www. or minimize adverse effects by early detection and treatment. Drug handbooks are helpful when you are trying to research specific information about a specific drug. This is a much more reliable source of drug information than memory. but without prioritization (eg. For example. A nursing textbook of pharmacology is comprehensive and gives you enough information to understand how drugs work. and nursing journals also contain information about drugs. any reported side effect is given rather than identifying the most common or most serious side effects). Mentally rehearse applying drug knowledge in nursing care by asking yourself. prevent. faster and more convenient access to effective treatment. Is the drug effective when used as recommended? 4. Lippincott’s Nursing Drug Guide. Two authoritative sources are the American Hospital Formulary Service and Drug Facts and Comparisons. Is the drug safe when used as instructed? Having drugs available OTC has potential advantages and disadvantages for consumers. Concentrate your study efforts on major characteristics. Keep an authoritative. Advantages include greater autonomy.com). Different references give you different information and are organized differently. When a drug is switched from prescription to OTC status. 5. Use your own words when taking notes or writing drug information cards.gov). Also.fda. including pharmacology textbooks. up-to-date drug reference readily available. preferably at work and home. Costs to consumers may increase because health insurance policies do not cover OTC drugs. so it is a good resource for new drugs. definitions of new terms. delaying treatment by a health care professional. and RxMed (http://www. answers to review questions. Understanding morphine makes learning about other opioid analgesics easier because they are compared with morphine. morphine is the prototype of opioid analgesics (see Chap. The former is published by the American Society of Health-System Pharmacists and updated periodically. 8. They are arranged alphabetically and assume you have a basic understanding of pharmacology.

810–816. B. D. K. List at least three authoritative sources of drug information. Changing the status of drugs from prescription to overthe-counter availability. Philadelphia: Lippincott Williams & Wilkins. & Sharp. Kelley’s Textbook of internal medicine. New England Journal of Medicine. Frequently asked questions. (2000). 14(5). Lipsky. Accessed 25 January 2003. 4th ed. P. M. What is the difference between local and systemic effects of drugs? 2. List at least three strategies for studying pharmacology. E. L. United States Food and Drug Administration. Journal of the American Board of Family Practice. Schwartz. (2001). .8 SECTION 1 INTRODUCTION TO DRUG THERAPY Review and Application Exercises 1. 345(11). (2001). 6. Humes (Ed. Why is it helpful to study prototypes of drug groups? 5. [On-line.gov/opacom/faqs/faqs. Geriatric clinical pharmacology. 362–367..] Available: http://www. 3095–3107. S.fda.). pp. From idea to market: The drug approval process. Why is it helpful for nurses to know the generic names of commonly used medications? 4.html. J. Can a client experience systemic effects of local drugs and local effects of systemic drugs? Why or why not? 3. SELECTED REFERENCES Brass. In H.

11. Green’s medications? What data will be important to collect before developing a plan for Mrs. 5. How do systemic drugs reach. After they act on cells. 4. 8. pharmacodynamics. metabolism. their common characteristics include the ability to: 9 . they must enter the body and be circulated to their sites of action (target cells). manufacture various products required to maintain cellular and bodily functions. pharmacokinetics. the risk for drug interactions and toxicity increases. an 89-year-old widow. 10. busy. they cannot add functions and activities. Describe drug-related and client-related variables that affect drug actions. These concepts and processes form the foundation of rational drug therapy and the content of this chapter.chapter 2 Basic Concepts and Processes Objectives AFTER STUDYING THIS CHAPTER. OVERVIEW ll body functions and disease processes and most drug actions occur at the cellular level. distribution. excretion) of the drugs she takes? What data will you collect to determine her risk? ᮣ What psychosocial factors could affect the therapeutic and adverse effects of Mrs. Discuss cellular physiology in relation to drug therapy. interact with. 7. Discuss general management of drug overdose and toxicity. Green’s age. 6. That is. Drugs are chemicals that alter basic processes in body cells. 2. Although cells differ from one tissue to another. Describe the main pathways and mechanisms by which drugs cross biologic membranes and move through the body. and leave body cells? How do people respond to drug actions? The answers to these questions are derived from cellular physiology. Discuss selected drug antidotes. When you visit as a home health nurse. To act on body cells. Reflect on: ᮣ Considering Mrs. drugs given for systemic effects must reach adequate concentrations in blood and other tissue fluids surrounding the cells. Differentiate between agonist drugs and antagonist drugs. lives alone and has recently started taking many heart medications. they must be eliminated from the body. “factories” (Fig. and other basic concepts and processes. pathways A and mechanisms of drug transport. Thus. Describe major characteristics of the receptor theory of drug action. Box 2–1). 3. Critical Thinking Scenario Mrs. what factors might alter the pharmacokinetics (absorption. and deliver those products to their appropriate destinations in the body. CELLULAR PHYSIOLOGY Cells are dynamic. Green? ᮣ When clients are taking many medications. Green. THE STUDENT WILL BE ABLE TO: 1. Describe how you will develop a plan to research possible drug interactions for any client. Describe each process of pharmacokinetics. 9. they take in raw materials. you assess therapeutic and adverse effects of her medications. They can stimulate or inhibit normal cellular functions and activities. She prides herself on being independent and able to manage on her own despite failing memory and failing health. 2–1. Discuss the clinical usefulness of measuring serum drug levels. Discuss mechanisms and potential effects of drug–drug interactions. Identify signs and symptoms that may occur with adverse drug effects on major body systems.

metabolism (biotransformation). For many drugs. drug molecules must cross numerous cell membranes. Figure 2–1 organelles. However. and rectum. peak and duration of drug actions. such as neurotransmitters and hormones DRUG TRANSPORT THROUGH CELL MEMBRANES Drugs. Schematic diagram of cell highlighting cytoplasmic • Exchange materials with their immediate environment • Obtain energy from nutrients • Synthesize hormones. and delivered to the small intestine (which has a large surface area for absorption of nutrients and drugs) before they are absorbed. therapeutic and adverse drug effects. fentanyl. circulate to the liver. Specific processes are absorption. these processes largely determine serum drug levels. blood flow to the site of administration. must reach and interact with or cross the cell membrane in order to stimulate or inhibit cellular function. Most oral drugs must be swallowed. as well as physiologic substances such as hormones and neurotransmitters. PHARMACOKINETICS Pharmacokinetics involves drug movement through the body (ie. sunscreens). and be excreted in urine. it also may decrease absorption because some drugs may move through the small intestine too rapidly to be absorbed. Drugs injected into subcutaneous (SC) or intramuscular (IM) tissues are usually absorbed more rapidly than oral drugs because they move directly from the injection site to the bloodstream. and other complex molecules • Duplicate themselves (reproduce) • Communicate with each other via various biologic chemicals. metabolism. mucous membranes. return to the bloodstream. To move through the body and reach their sites of action. eye. nose. circulate to the kidneys. Overall. systemic absorption occurs from the mucosa of the oral cavity. estrogen. . 2–2). scopolamine). perform their action. GI function. systemic effects). Also. For example. and excretion. Rapid movement through the stomach and small intestine may increase drug absorption by promoting contact with absorptive mucous membrane. and other variables. 2–3 and Box 2–2). route of administration. Drugs injected intravenously (IV) do not need to be absorbed because they are placed directly into the bloodstream. intensity is determined by the extent of absorption. Other absorptive sites include the skin. Most drugs are given for effects on body cells that are distant from the sites of administration (ie. Absorption Absorption is the process that occurs from the time a drug enters the body to the time it enters the bloodstream to be circulated. The lungs have a large surface area for absorption of anesthetic gases and a few other drugs. enzymes. liver. and excretion. Systemic absorption is minimal from intact skin but may be considerable when the skin is inflamed or damaged. “what the body does to the drug”) to reach sites of action. metabolism. Several transport pathways and mechanisms are used to move drug molecules through the body (Fig. the presence of food in the stomach slows the rate of absorption and may decrease the amount of drug absorbed. the presence of food or other drugs. neurotransmitters. Liquid medications are absorbed faster than tablets or capsules because they need not be dissolved. Drugs absorbed through mucous membranes pass directly into the bloodstream. a number of drugs have been formulated in adhesive skin patches for absorption through the skin (eg. circulate to their target cells. vagina. dissolved in gastric fluid.10 SECTION 1 INTRODUCTION TO DRUG THERAPY Cell membrane Cytoplasm Lysosomes Chromatin Nucleus Endoplasmic reticulum Ribosomes Golgi apparatus Mitochondria distribution. Onset of drug action is largely determined by the rate of absorption. and lungs. drug half-life. Absorption is rapid from IM sites because muscle tissue has an abundant blood supply. onset. including dosage form. Numerous factors affect the rate and extent of drug absorption. nitroglycerin. re-enter the bloodstream (usually as metabolites). An intravenous drug is virtually 100% bioavailable. molecules of most oral drugs must cross the membranes of cells in the gastrointestinal (GI) tract. and capillaries to reach the bloodstream. reach drug-metabolizing enzymes in liver cells. leave the bloodstream and attach to receptors on cells. Dosage form is a major determinant of a drug’s bioavailability (the portion of a dose that reaches the systemic circulation and is available to act on body cells). and other important aspects of drug therapy. Some drugs applied to mucous membranes also are given for local effects. clonidine. Most drugs applied to the skin are given for local effects (eg. an oral drug is virtually always less than 100% bioavailable because some is not absorbed from the GI tract and some goes to the liver and is partially metabolized before reaching the systemic circulation. structural proteins. and excretion (Fig.

a small amount of carbohydrate is stored within the cell as glycogen. which covers the entire surface of the cell. electrolytes (potassium. consists of a thin. The nucleus might be called the “manager” of cellular activities because it regulates the type and amount of proteins. It is composed of water. proteins. Glucose is present in extracellular fluid and readily available to supply the cell’s need for energy. proteins. insulin). sodium. is soluble in water. Lysosomes are membrane-enclosed vesicles that contain enzymes capable of digesting nutrients (proteins. Integral proteins penetrate through the entire membrane so that each end is available to interact with other substances. inner core of protein (called proteoglycans) often are attached to and cover the entire outside surface of the cell. However. the “carbohydrate coat” of some cells attaches to the carbohydrate coat of other cells and thereby connects cells to each other. and carbohydrates. a storage form of glucose that can be rapidly converted when needed. triglycerides. which then move out of the Golgi complex into the cytoplasm and. The cell membrane. the glyco portion protrudes to the outside of the cell.CHAPTER 2 BASIC CONCEPTS AND PROCESSES 11 BOX 2–1 CELL STRUCTURES AND FUNCTIONS activated by enzyme inhibitors and excessive tissue destruction is prevented. Glycoproteins composed of carbohydrate around a small. The lipid layer is composed of phospholipid (fatty acid and phosphate) molecules. Third. many have a negative electrical charge which gives most cells an overall negative surface charge that repels other negatively charged substances. Some of these proteins provide structural channels or pores through which water and water-soluble substances (eg. electrolytes. Cell membrane proteins. Carbohydrates play a minor role in cell structure. and calcium ions) can diffuse between extracellular and intracellular fluids. this portion of the membrane allows easy penetration of fat-soluble substances such as oxygen and alcohol. These include enzymes that synthesize glycogen. Thus. the enzymes are in- . The protein portion protrudes on the intracellular side of the cell membrane. These enzymatic proteins come into direct contact with other substances in the cell fluid and catalyze chemical reactions within the cell. Cell membrane carbohydrates occur mainly in combination with proteins (glycoproteins) or lipids (glycolipids). Normally. cellular enzymes. enzymes. Second. and steroids and those that detoxify drugs and other chemicals. The phosphate end of each phospholipid molecule. after an appropriate stimulus. foreign substances (eg. They consist of “physical” proteins that form the structure of cells and “chemical” proteins that function mainly as enzymes within the cell. Others act as carriers to transport substances that otherwise could not penetrate the lipid layer of the membrane. The ER is important in the production of hormones by glandular cells and the production of plasma proteins and drug-metabolizing enzymes by liver cells. which synthesize enzymes and other proteins. These proteins function as enzymes and other substances that regulate intracellular function. located on the external surface and in contact with the tissue fluids surrounding the cell. transmission of electrochemical impulses in nerve and muscle cells). Mitochondria generate energy for cellular activities and require oxygen. Peripheral proteins do not penetrate the cell membrane. but a major role in cell nutrition. Water makes up 70% to 85% of most cells. The fatty acid end of the phospholipid molecule. and helps regulate growth and proliferation. and bicarbonate). lipids. the membrane around the lysosome breaks and the enzymes (hydrolases) are released. include integral and peripheral proteins. When a cell becomes worn out or damaged. potassium. mainly phospholipids and cholesterol. It also packages these substances into secretory granules. As a result. In addition. most of which are combined with a carbohydrate as glycoproteins. participates in electrical events that occur in nerve and muscle cells. Protoplasm comprises the internal environment of body cells. bacteria). form the membranes that separate structures inside the cell and the cell itself from surrounding cells and body fluids. They are usually attached to the intracellular side of the membrane and to integral proteins. Proteins comprise 10% to 20% of the cell mass. many of the carbohydrates act as receptor molecules for binding hormones (eg. damaged cellular structures. Lipids. The Golgi complex stores hormones and other substances produced by the ER. located in the middle of the membrane. separates intracellular contents from the extracellular environment. The endoplasmic reticulum (ER) contains ribosomes. dangling outward from the cell surface. sulfate. is soluble only in fat. The cell membrane. and other chemicals are dissolved or suspended in the water. and other substances to be produced. double layer of lipids interspersed with proteins (see Fig. phosphate. but is impermeable to water-soluble substances such as ions and glucose. carbohydrates. Still others act as enzymes to catalyze chemical reactions within the cell. a complex structure composed of phospholipids. First. The receptor–hormone combination then activates the attached inner core of protein to perform its enzymatic or other functions in the cell. lysosomal contents also are released into extracellular spaces. and the cell itself. cholesterol and carbohydrates. Electrolytes provide chemicals for cellular reactions and are required for some processes (eg. magnesium. destroying surrounding cells. The cytoplasm surrounds the nucleus and contains the working units of the cell. the carbohydrate molecules are free to interact with extracellular substances and perform several important functions. fats). provides receptors for hormones and other biologically active substances. 2–3). are released from the cell through the process of exocytosis.

or attaching to carrier proteins. fat. Once a drug is injected or absorbed into the bloodstream. Only the free or unbound portion of a drug acts on body cells. etc. which act as carriers. and excretion. through gaps between the cells that form capillary walls. GI tract) Excretion (eg. which are Cell membrane Lipid-soluble drugs dissolve in the lipid layer of the cell membrane and diffuse into or out of the cell. and excretion. . oral. 67). Drug molecules cross cell membranes to move into and out of body cells by directly penetrating the lipid layer.) Drug Absorption (from site of administration into plasma) Storage in Tissue (eg. only drugs that are lipid soluble or have a transport system can cross the blood–brain barrier and reach therapeutic concentrations in brain tissue. parenteral. and skin is usually slower. and excretion. Metabolism Metabolism is the method by which drugs are inactivated or biotransformed by the body. liver. and kidneys. sweat. feces) Figure 2–2 Entry and movement of drug molecules through the body to sites of action. expired air. Distribution to other internal organs. Drug distribution into the central nervous system (CNS) is limited because the blood–brain barrier. Drug molecules bound to plasma proteins are pharmacologically inactive because the large size of the complex prevents their leaving the bloodstream through the small openings in capillary walls and reaching their sites of action. During lactation. fat. Figure 2–3 Drug transport pathways. As the free drug acts on cells. more even blood levels and reduce the risk of toxicity. Nucleus Potassium Carrier proteins attach to drug molecules and move them across cell membranes. Protein binding allows part of a drug dose to be stored and released as needed. metabolism. body fat) PLASMA Bound Drug Free Drug Site of Action (eg. an active drug is changed into one or more inactive metabolites. kidney. many drugs enter breast milk and may affect the nursing infant. muscle. These storage mechanisms maintain lower. This barrier usually acts as a selectively permeable membrane to protect the CNS. metabolism. such as the heart. However. or other body tissues and released gradually when plasma drug levels fall. Most often. Drug distribution during pregnancy and lactation is also unique (see Chap. most drugs cross the placenta and may affect the fetus. it also can make drug therapy of CNS disorders more difficult because drugs must pass through cells of the capillary wall rather than between cells. Cytoplasm Sodium Gated channels regulate movement of ions. Distribution Distribution involves the transport of drug molecules within the body. liver. limits movement of drug molecules into brain tissue.12 SECTION 1 INTRODUCTION TO DRUG THERAPY Drug Administration (eg. An important factor in drug distribution is protein binding (Fig. which is composed of capillaries with tight walls. lung. 2–4). During pregnancy. mainly albumin. Most drugs form a complex with plasma proteins. Some drugs also are stored in muscle. Most drug molecules enter and leave the bloodstream at the capillary level. the decrease in plasma drug levels causes some of the bound drug to be released. Drugs are distributed rapidly to organs receiving a large blood supply. Drugs that are highly bound to plasma proteins or stored extensively in other tissues have a long duration of action. Distribution depends largely on the adequacy of blood circulation. cell receptor) Metabolism (eg. it is carried by the blood and tissue fluids to its sites of pharmacologic action. As a result. diffusing through open or gated channels. metabolism.

and conjugation with endogenous sub- . Hepatic drug metabolism or clearance is a major mechanism for terminating drug action and eliminating drug molecules from the body. which are able to dissolve in the lipid layer of the cell membrane. facilitated diffusion. even oral tablets and capsules that must be sufficiently water soluble to dissolve in the aqueous fluids of the stomach and small intestine. a characteristic that aids their movement across cell membranes. so that the drug moves (from capillaries) into the fluids surrounding the cells or into the cells themselves. when the gates open. when the gates open. The cytochrome P450 system consists of 12 groups or families. blocks the channel opening) to prevent additional ion movement. sodium and potassium) use this pathway. Bound drug (A–D) stays in bloodstream and is pharmacologically inactive. Individual members of the groups. nine of which metabolize endogenous substances and three of which metabolize drugs. Chemical gating (eg. On sodium channels. plasma. The gate is a flap of protein that opens for a few milliseconds to allow ion movement across the cell membrane. Most systemic drugs are formulated to be lipid soluble so they can move through cell membranes. red blood cells. A second pathway involves passage through protein channels that go all the way through the cell membrane. mainly albumin (A). a drug’s structure determines which carrier will transport it. can excrete only water-soluble substances. Only a few drugs are able to use this pathway because most drug molecules are too large to pass through the small channels. Therefore. All of the carrier proteins are selective in the substances they transport. potassium ions (K+) move from the cell into extracellular fluid. sodium ions (Na+) move from extracellular fluid into the cell. However. by neurotransmitters such as acetylcholine) is very important in the transmission of signals from one nerve cell to another and from nerve cells to muscle cells to cause muscle contraction. Of the many drugs metabolized by the liver. In active transport. They are used. and to carry drug molecules from the blood into renal tubules. involves movement of a drug from an area of higher concentration to one of lower concentration. which are the primary excretory organs. The most common pathway is direct penetration of the membrane by lipid-soluble drugs. the gates are located on the inside of the cell membrane. lungs. This process requires a carrier substance and the release of cellular energy. are complex proteins with binding sites for drug molecules (and endogenous substances). With voltage gating. These transport systems are an important means of moving drug molecules through the body. each of which metabolizes specific drugs. located within hepatocytes. Facilitated diffusion is a similar process. a chemical substance (a ligand) binds with the protein forming the channel and changes the shape of the protein to open or close the gate. The stimulus for opening and closing the gates may be voltage gating or chemical (also called ligand) gating. for example. the CYP3 group of enzymes is thought to metabolize about 50%. one function of metabolism is to convert fat-soluble drugs into water-soluble metabolites. These enzymes. Other drugs (called prodrugs) are initially inactive and exert no pharmacologic effects until they are metabolized. to carry hormones to their sites of action inside body cells.CHAPTER 2 BASIC CONCEPTS AND PROCESSES 13 BOX 2–2 DRUG TRANSPORT PATHWAYS AND MECHANISMS The third pathway involves carrier proteins that transport molecules from one side of the cell membrane to the other. Bloodstream A D A D A D D D A D D Tissue fluid around cells D Figure 2–4 Plasma proteins. Small ions (eg. the kidneys. then closes (ie. are further categorized. Passive diffusion. Some active drugs yield metabolites that are also active and that continue to exert their effects on body cells until they are metabolized further or excreted. and the CYP1 group about 5%. the gates are located on the outside of the cell membrane. This promotes movement of the drug into the bloodstream. When the drug is circulated. For example. They catalyze the chemical reactions of oxidation. Most drugs are metabolized by enzymes in the liver (called the cytochrome P450 [CYP] or the microsomal enzyme system). Free drug (D) can leave the bloodstream and act on body cells. CYP2C9. CYP2 and CYP3. the concentration is higher in the blood than in body cells. except that drug molecules combine with a carrier substance. drugs are transported to and from target cells by such mechanisms as passive diffusion. after oral administration. The three groups that metabolize drugs are labeled CYP1. act as carriers for drug molecules (D). and active transport. the CYP2 group about 45%. the initial concentration of a drug is higher in the gastrointestinal tract than in the blood. then excreted. or CYP3A4 enzymes. such as an enzyme or other protein. reduction. hydrolysis. the electrical potential across the cell membrane determines whether the gate is open or closed. drug molecules are moved from an area of lower concentration to one of higher concentration. Passive diffusion continues until a state of equilibrium is reached between the amount of drug in the tissues and the amount in the blood. For example. many drugs are metabolized by CYP2D6. kidneys. Most drugs are lipid soluble. On potassium channels. With chemical gating. but their movement is regulated by specific channels with a gating mechanism. and GI mucosa also contain drug-metabolizing enzymes. Pathways There are three main pathways of drug movement across cell membranes. Mechanisms Once absorbed into the body. the most common mechanism. to carry oral drugs from the intestine to the bloodstream.

digoxin. drug levels decline as the drug is eliminated (ie. • To monitor unexpected responses to a drug dose. measuring serum drug levels is useful in several circumstances: • When drugs with a low or narrow therapeutic index are given. others are excreted in bile. bowel. this is largely determined by the drug dose and how well it is absorbed into the bloodstream. Enzyme inhibition occurs within hours or days of starting an inhibiting agent. and eventually excreted in urine. then eliminated in feces. A toxic concentration is an excessive level at which toxicity occurs. This could be either a lack of therapeutic effect or increased adverse effects. in people with impaired blood flow to the liver or severe hepatic or cardiovascular disease. is the time required for the serum concentration of a drug to decrease by 50%. acetaminophen). also called elimination half-life. These are drugs with a narrow margin of safety because their therapeutic doses are close to their toxic doses (eg. estrogens. a gastric acid suppressor. When a drug is given at a stable dose. metabolized. smaller doses of the slowly metabolized drug may be needed to avoid adverse reactions and toxicity from drug accumulation. Excretion Excretion refers to elimination of a drug from the body. or slow metabolism that allows the drug to accumulate in the body. with only part of a drug dose reaching the systemic circulation for distribution to sites of action. and skin). therapeutic effects. cortisol. drug action stops when drug levels fall below the MEC. Enzyme induction accelerates drug metabolism because larger amounts of the enzymes (and more binding sites) allow larger amounts of a drug to be metabolized during a given time. lithium. In this case. • To document the serum drug levels associated with particular drug dosages. enough drug to be beneficial. aminoglycoside antibiotics. inhibits several CYP enzymes (eg. 2–5).14 SECTION 1 INTRODUCTION TO DRUG THERAPY stances. testosterone. which is the goal of drug therapy—that is. lead to accumulation of numerous drugs and may cause severe adverse effects if dosage is not reduced. It is determined primarily by the drug’s rates of metabolism and excretion. Some oral drugs are not absorbed and are excreted in the feces. The skin has minimal excretory function. The lungs mainly remove volatile substances. is a strong inducer of CYP 1A and 3A enzymes Metabolism also can be decreased or delayed in a process called enzyme inhibition. onset of action occurs when the drug level reaches the MEC. and vitamin D). and duration of drug action. such as anesthetic gases. Cimetidine. absorption. When multiple doses of a drug are given (eg. 2C. serum levels indicate the onset. metabolized and excreted) from the body. A minimum effective concentration (MEC) must be present before a drug exerts its pharmacologic action on body cells. Toxic concentrations may stem from a single large dose. Factors impairing excretion. half-life. A drug with a short half-life requires more frequent administration than one with a long half-life. Rapid metabolism may also increase the production of toxic metabolites with some drugs. (eg. 1A2. larger doses of the rapidly metabolized drug may be required to produce or maintain therapeutic effects. Rifampin. Effective excretion requires adequate functioning of the circulatory system and of the organs of excretion (kidneys. Between these low and high concentrations is the therapeutic range. The drug level continues to climb as more of the drug is absorbed. Serum Half-Life Serum half-life. but not enough to be toxic. lungs. reabsorbed from the small intestine. bioavailability. they are absorbed from the GI tract and carried to the liver through the portal circulation. repeated small doses. long-lasting conditions). For most drugs. and 3A) and can greatly decrease drug metabolism. Then. Some drugs are extensively metabolized in the liver. The rate of drug metabolism also is reduced in infants (their hepatic enzyme system is immature). Drugs that induce enzyme production also may increase the rate of metabolism for endogenous steroidal hormones (eg. • When a drug overdose is suspected. or possible adverse effects. The duration of action is the time during which serum drug levels are at or above the MEC. and the rates of metabolism and excretion. four or five halflives are required to achieve steady-state concentrations and develop equilibrium between tissue and serum concentra- . an antituberculosis drug. returned to the liver (called enterohepatic recirculation). theophylline). Although there may still be numerous drug molecules in the body. peak. which most often occurs with concurrent administration of two or more drugs that compete for the same metabolizing enzymes. because new enzyme proteins must be synthesized. especially severe renal disease. It reflects dosage. When drugs are given orally. such as glucuronic acid or sulfate. some drugs stimulate liver cells to produce larger amounts of drug-metabolizing enzymes (a process called enzyme induction). until it reaches its highest concentration and peak drug action occurs. and in people who are malnourished or on low-protein diets. for chronic. When a single dose of a drug is given. This is called the first-pass effect or presystemic metabolism. Some drugs or metabolites are excreted in bile. As a result. the goal is usually to give sufficient doses often enough to maintain serum drug levels in the therapeutic range and avoid the toxic range. enzyme induction does not occur for 1 to 3 weeks after an inducing agent is started. Serum Drug Levels A serum drug level is a laboratory measurement of the amount of a drug in the blood at a particular time (Fig. However. Most drugs are excreted by the kidneys and eliminated unchanged or as metabolites in the urine. With chronic administration. In clinical practice.

Drug action starts when enough drug is absorbed to reach the minimum effective concentration (MEC). Because almost all cellular functions are catalyzed by enzymes. To maintain steady-state conditions. “what the drug does to the body”). If concentrations above 25 units/mL are toxic and no more drug is given. continues as long as the serum level is above the MEC. Because maximal therapeutic effects do not occur until equilibrium is established.CHAPTER 2 BASIC CONCEPTS AND PROCESSES 15 Toxic concentration Serum Drug Levels Peak serum drug level ti o n ab Therapeutic concentration Drug action stops eli mi na tio n Dr rp ug Drug action starts Dr ug so Duration of drug action Minimum effective concentration (MEC) Administration of an oral drug Time (hours) Drug action in relation to serum drug levels and time after a single does. The goal of drug therapy is to maintain serum drug levels in the therapeutic range. sodium–potassium adenosine triphosphatase) or structural processes (eg. all drug actions occur at the cellular level. tubulin). when a drug is discontinued. wanes as drug molecules are metabolized and excreted (if no more doses are given). how long will it take for the blood level to reach the nontoxic range? . Therapeutic concentration Duration of drug action Drug action stops Minimum effective concentration (MEC) First dose of drug enters body Time (days) Drug is eliminated from the body Drug action in relation to serum drug levels with repeated doses. The drug’s half-life is 1 hour. drug-induced changes can markedly increase or decrease the rate of cellular metabolism. acetylcholinesterase). For example. Specific receptors include enzymes involved in essential metabolic or regulatory processes (eg. and stops when the serum level drops below the MEC. inactivation. or other alterations of intracellular enzymes. it is eliminated gradually over several half-lives. hormones and neurotransmitters) that normally regulate cell functions. When a drug dose is changed. and other metabolic activities. an epinephrine–receptor complex increases the activity of the intracellular enzyme adenyl cyclase. some drugs are not fully effective for days or weeks. 2–6). Toxic concentration Serum Drug Levels Steady-state serum drug level Regularly scheduled doses Drug action starts Last dose Waning serum drug levels Figure 2–5 Serum drug levels with single and multiple oral drug doses. Nursing Notes: Apply Your Knowledge A client has a drug level of 100 units/mL. which then causes the formation of cyclic adenosine PHARMACODYNAMICS Pharmacodynamics involves drug actions on target cells and the resulting alterations in cellular biochemical reactions and functions (ie. proteins involved in transport (eg. the resulting drug–receptor complex initiates physiochemical reactions that stimulate or inhibit normal cellular functions. DNA) involved in cellular protein synthesis. and nucleic acids (eg. One type of reaction involves activation. When drug molecules bind with receptor molecules. most drugs exert their effects by chemically binding with receptors at the cellular level (Fig. Receptors are mainly proteins located on the surfaces of cell membranes or within cells. the amount of drug given must equal the amount eliminated from the body. an additional four to five halflives are required to re-establish equilibrium. Receptor Theory of Drug Action Like the physiologic substances (eg. reproduction. tions. As previously stated. dihydrofolate reductase.

Agonists are drugs that produce effects similar to those produced by naturally occurring hormones. Thus. such as receptors for opiates and benzodiazepines in the brain and subgroups of receptors for epinephrine in the heart (beta1-adrenergic receptors) and lungs (beta2-adrenergic receptors). can initiate any one of many different intracellular actions. For example. and its binding to a drug molecule may open or close ion channels. movement of the ions into the cells may alter intracellular functions. the pharmacologic effects are those due to either agonism or antagonism. and circulate to the liver for metabolism and the kidneys for excretion. In this instance. chemical characteristics determine drug actions and pharmacologic effects. This prevents natural body substances or other drugs from occupying the receptor sites and activating cell functions. Another major factor is the concentration of drug molecules that reach receptor sites in body tissues. increasing the drug dosage increases the pharmacologic effects. if only a few receptors are available for many drug molecules. This action inhibits neuronal excitability and function. for example. potassium channels may open and allow movement of potassium ions out of the cell. the cell becomes less responsive to the agonist (a process called receptor desensitization . In muscle cells. prolonged stimulation of body cells with an excitatory agonist usually reduces the number or sensitivity of receptors. and insulin. increasing the drug dosage produces no additional pharmacologic effect. such as receptors for epinephrine and norepinephrine (whether received from stimulation of the sympathetic nervous system or administration of drug formulations) and receptors for hormones. monophosphate (cAMP). serotonin) that regulate many physiologic processes. Receptors are dynamic cellular components that can be synthesized by body cells and altered by endogenous substances and exogenous drugs. Conversely. As a result. The site and extent of drug action on body cells are determined primarily by specific characteristics of receptors and drugs. The receptor protein is a structural component of the cell membrane. These substances stimulate or inhibit cellular function. Because all drugs are chemical substances. neurotransmitters. and other substances. 3. return to the bloodstream. Receptors vary in type. For example. the exact effect depending on the type of cell. Drugs vary even more widely than receptors. the chemical binding is reversible). including growth hormone. A second type of reaction involves changes in the permeability of cell membranes to one or more ions. The number of receptor sites available to interact with drug molecules also affects the extent of drug action. release. For example. few drug effects occur. or inactivation of the neurohormones (eg. 2. acetylcholine. In this instance. Antagonists are drugs that inhibit cell function by occupying receptor sites. A third reaction may modify the synthesis. receptors may be saturated. Minor changes in drug structure may produce major changes in pharmacologic effects. depending on the type of receptor activated. both are agonists. if most receptor sites are occupied. cAMP. At other times. Some occur in fewer body tissues. Agonists may accelerate or slow normal cellular processes. all body cells do not respond to all drugs. and only those drugs able to bond chemically to the receptors in a particular body tissue can exert pharmacologic effects on that tissue. such as the direct effect of calcium ions in stimulating muscle contraction. When drug molecules chemically bind with cell receptors. Additional elements and characteristics of the receptor theory include the following: 1. epinephrine-like drugs act on the heart to increase the heart rate. thyroid hormone. Most types occur in most body tissues. if many receptors are available but only a few are occupied by drug molecules. The receptor is often described as a lock into which the drug molecule fits as a key. and acetylcholine-like drugs act on the heart to slow the heart rate. and functional capacity. number. many different types of receptors have been identified. location. norepinephrine. Drug molecules (Da and Db) also interact with receptors to stimulate or inhibit cellular function. in turn. Drugand client-related variables that affect drug actions are further described below. Presumably. Receptor type and location influence drug action. This usually causes the cell membrane to depolarize and excite the cell. Thus.16 SECTION 1 INTRODUCTION TO DRUG THERAPY Cell membrane H Cytoplasm H H Da H Receptor site Db NT Nucleus H NT NT Da Db H Receptor site Figure 2–6 Cell membrane contains receptors for physiologic substances such as hormones (H) and neurotransmitters (NT). a minimal number of receptors must be occupied by drug molecules to produce pharmacologic effects. Once drug action occurs. In nerve cells. a drug’s chemical structure affects its ability to reach tissue fluids around a cell and bind with its cell receptors. For example. sodium or calcium ion channels may open and allow movement of ions into the cell. drug molecules may detach from receptor molecules (ie. even though virtually all cell receptors are exposed to any drug molecules circulating in the bloodstream.

If the antagonist is suddenly reduced or stopped. pyrimidines) and that can be incorporated into cellular constituents. Osmotic diuretics (eg. Drug–Diet Interactions Food may alter the absorption of oral drugs. One such interaction occurs between tyraminecontaining foods and monoamine oxidase (MAO) inhibitor drugs. Interactions that alter drug absorption can be minimized by spacing food and medications. renal. Because dosage includes the amount of the drug and the frequency of administration. For some drugs. older adults. current clinical trials are including more representatives of these groups. When tablets or capsules are taken with or soon after food. potency. food slows absorption by slowing gastric emptying time and altering GI secretions and motility. however. other groups of people (eg. size. Route of Administration Routes of administration affect drug actions and responses largely by influencing absorption and distribution. In any client. which act chemically to neutralize the hydrochloric acid produced by gastric parietal cells and thereby raise the pH of gastric fluid 2. the IM route also produces drug action within a few minutes because muscles have a large blood supply. In addition.and client-related variables. For example. The dosage of a particular drug depends on many characteristics of the drug (reason for use. some foods contain substances that react with certain drugs. therefore. the IV route is most effective because the drug is injected directly into the bloodstream. Thus. Antacids. pharmacokinetics. Metal chelating agents. Doses that produce signs and symptoms of toxicity are called toxic doses. mannitol). However. which increase the osmolarity of plasma and pull water out of tissues into the bloodstream 3. a strong vasoconstrictive agent. route of administration. and number of doses. cause the drug does not reach an adequate concentration at target cells. Nonreceptor Drug Actions Relatively few drugs act by mechanisms other than combination with receptor sites on cells. weight. Tyramine causes the release of norepinephrine. Therefore. norepinephrine is active for only a few milliseconds before it is inactivated by MAO. certain drugs or dosage forms are better absorbed with certain types of meals. and other factors. purines. The oral route usually produces slower drug action than parenteral routes. toxicity (poisoning) may occur. some of which are described in the following sections. whether the drug is applied to skin or mucous membranes. the cell becomes excessively responsive to an agonist (a process called receptor upregulation). Dosage is a major determinant of drug actions and responses. ingesting tyramine-containing foods with an MAO inhibitor may produce severe hypertension or intracranial VARIABLES THAT AFFECT DRUG ACTIONS Expected responses to drugs are largely based on those occurring when a particular drug is given to healthy adult men (18 to 65 years of age) of average weight (150 lb [70 kg]).CHAPTER 2 BASIC CONCEPTS AND PROCESSES 17 or down-regulation). In other instances. Absorption and action of topical drugs vary according to the drug formulation. Several anticancer drugs act by this mechanism. This interferes with normal cell functioning. These dosages usually produce a mixture of therapeutic and adverse effects. In many instances. Dosages recommended in drug literature are usually those that produce particular responses in 50% of the people tested. and function of cardiovascular. responses may be altered by both drug. which combine with toxic metals (eg. Drug-Related Variables Dosage Although the terms dose and dosage are often used interchangeably. Doses that cause death are called lethal doses. Drugs that are structurally similar to nutrients required by body cells (eg. children. drug molecules are delivered to absorptive sites in the small intestine more slowly. such as nucleic acids. These changes in receptors may explain why some drugs must be tapered in dosage and discontinued gradually if withdrawal symptoms are to be avoided. a fatty meal increases the absorption of some sustained-release forms of theophylline. overdosage may occur with a single large dose or with chronic ingestion of smaller amounts. and hepatic systems). Normally. dose indicates the amount to be given at one time and dosage refers to the frequency. and others) and of the recipient (age. lead) to form a complex that can be more readily excreted. however. However. they dissolve more slowly. from the adrenal medulla and sympathetic neurons. If the amount is too small or administered infrequently. For rapid drug action and response. women. 4. These include: 1. both therapeutic and adverse. state of health. and clients with diseases or symptoms that the drugs are designed to treat) receive drugs and respond differently than healthy adult men. different ethnic or racial groups. the recommended dosages are intended only as guidelines for individualizing dosages. no pharmacologic action occurs be- . Food also may decrease absorption by combining with a drug to form an insoluble drug–food complex. If the amount is too large or administered too often. because MAO inhibitor drugs prevent inactivation of norepinephrine. dosage form. Prolonged inhibition of normal cellular functions with an antagonist may increase receptor number or sensitivity.

4. Example: acetaminophen (non-opioid analgesic) + codeine (opioid analgesic) → increased analgesia 3. a frequently used oral anticoagulant. The sodium bicar- How Can You Avoid This Medication Error? Mrs. Example: aluminum or magnesium hydroxide (antacids) + oral tetracycline (an antibiotic) → binding of tetracycline to aluminum or magnesium. Naloxone molecules displace morphine molecules from their receptor sites on nerve cells in the brain so that the morphine molecules cannot continue to exert their depressant effects. Example: cimetidine inhibits CYP 1A.18 SECTION 1 INTRODUCTION TO DRUG THERAPY hemorrhage. large amounts of spinach and other green leafy vegetables may offset the anticoagulant effects and predispose the person to thromboembolic disorders. some. Several drugs (eg. and the overall effect is the same as taking a larger dose of the displaced drug. 2. Additive effects occur when two drugs with similar pharmacologic actions are taken. Beecher. aged cheeses. drugs metabolized by the same enzymes may compete for enzyme binding sites and there may not be enough binding sites for two or more drugs. Example: phenobarbital (a barbiturate) + warfarin (an anticoagulant) → decreased effects of warfarin 4. phenytoin. You give her the tablet with a large glass of grapefruit juice and caution her to swallow the tablet whole. such as milk and cheese. some drugs induce or inhibit the metabolism of other drugs. MAO inhibitors include the antidepressants isocarboxazid and phenelzine and the antineoplastic procarbazine. an antibiotic. wine. become pharmacologically active. and warfarin). The displaced drug then becomes pharmacologically active. and 3A drug-metabolizing enzymes in the liver and therefore interferes with the metabolism of many drugs (eg. tricyclic antidepressants. In some situations. Her blood pressure is 148/70. Tyramine-rich foods to be avoided by clients taking MAO inhibitors include beer. a drug that is a specific antidote is given to antagonize the toxic effects of another drug. chicken livers. Increased excretion occurs when urinary pH is changed and renal reabsorption is blocked. Examples of such interactions are as follows: 1. a calcium channel blocker. Two days later Mrs. The basic cause of many drug–drug interactions is altered drug metabolism. a 76-year-old nursing home client. freed from their bound form. Activation of drug-metabolizing enzymes in the liver increases the metabolism rate of any drug metabolized primarily by that group of enzymes. When these drugs are given concurrently with cimetidine. A third interaction occurs between tetracycline. and foods containing vitamin K. they are likely to cause adverse and toxic effects. This increase occurs because the molecules of the displaced drug. For example. has just had a change in her antihypertension medications to felodipine 10 mg qd. some antidysrhythmics. and cigarette smoking are known enzyme inducers. and pickled herring. Because vitamin K antagonizes the action of warfarin. calcium channel blockers. causing decreased absorption and decreased antibiotic effect of tetracycline 3. Increased Drug Effects Interactions that can increase the therapeutic or adverse effects of drugs are as follows: 1. Example: ethanol + sedative drug → increased sedation 2. Beecher’s blood pressure is 96/60. yeast products. Example: aspirin (an anti-inflammatory/analgesic/ antipyretic agent) + warfarin (an anticoagulant) → increased anticoagulant effect Decreased Drug Effects Interactions in which drug effects are decreased are grouped under the term antagonism. The drug combines with the calcium in milk products to form an insoluble. benzodiazepine antianxiety and hypnotic drugs. occur when the interacting drugs are given at or near the same time. Protein binding is also the basis for some important drug–drug interactions. Example: sodium bicarbonate + phenobarbital → increased excretion of phenobarbital. especially those affecting the absorption of oral drugs. and dairy products. . An interaction may occur between warfarin. A drug with a strong attraction to protein-binding sites may displace a less tightly bound drug. 2C. rifampin). Most interactions occur whenever the interacting drugs are present in the body. Displacement of one drug from plasma protein-binding sites by a second drug increases the effects of the displaced drug. Example: naloxone (a narcotic antagonist) + morphine (a narcotic or opioid analgesic) → relief of opioidinduced respiratory depression. These drugs are infrequently used nowadays. unabsorbable compound that is excreted in the feces. ethanol. Drug–Drug Interactions The action of a drug may be increased or decreased by its interaction with another drug in the body. Also. Decreased intestinal absorption of oral drugs occurs when drugs combine to produce nonabsorbable compounds. partly because of this potentially serious interaction and partly because other effective drugs are available. theophylline. Synergism or potentiation occurs when two drugs with different sites or mechanisms of action produce greater effects when taken together than either does when taken alone. Interference by one drug with the metabolism or elimination of a second drug may result in intensified effects of the second drug. beta blockers and antiseizure drugs.

As another example of genetic variation in drug metabolism. decreased glomerular filtration rate. When given the same drug in the same dose. Changes in the cardiovascular system include decreased cardiac output and therefore slower distribution of drug molecules to their sites of action. some people experience inadequate therapeutic effects. It was further established that humans may acetylate the drug rapidly or slowly. many drugs are metabolized more slowly. rapid acetylators may need larger-than-usual doses to achieve therapeutic effects. depending largely on genetically controlled differences in acetyltransferase activity. For example. Newborn infants (birth to 1 month) also handle drugs inefficiently. genes determine the types and amounts of proteins produced in the body. drugs cross the placenta and may harm the fetus. The ratio between the amount of drug given and body weight influences drug distribution and concentration at sites of action. and decreased motility. Genetic characteristics that alter any of these proteins can alter drug pharmacokinetics or pharmacodynamics. and excretion. but liver function and the blood–brain barrier are still immature. Clinically. In children. One of the earliest genetic variations to be identified derived from the observation that some people taking usual doses of isoniazid (an antitubercular drug). physiologic changes may alter all pharmacokinetic processes. Thus. cell membranes. they interact with proteins (eg. Thus. however. The reaction is catalyzed by a hepatic drug-metabolizing enzyme called acetyltransferase. hydralazine (an antihypertensive agent). there is decreased blood flow. blood flow and metabolizing enzymes are decreased. decreased blood flow. Genetic and Ethnic Characteristics Client-Related Variables Age The effects of age on drug action are most pronounced in neonates. and older adults. drug action depends largely on age and developmental stage. and excretion differ markedly in neonates. In the liver. provided that their renal. possibilities for interactions among drugs and between drugs and diseased organs are greatly multiplied. All of these changes tend to slow excretion and promote accumulation of drugs in the body. and with other proteins (eg. hepatic. In the kidneys. As a result. and drug receptor sites) to reach their sites of action. Despite these changes. tissues. infants. drug-metabolizing enzymes in the liver and other organs) to be biotransformed and eliminated from the body. Children (1 to 12 years) experience a period of increased activity of drug-metabolizing enzymes so that some drugs are rapidly metabolized and eliminated. When most drugs enter the body. Although the onset and duration of this period are unclear. Therefore. including increased toxicity. there is increased awareness that genetic and ethnic characteristics are important factors and that diverse groups must be included in clinical trials. Research established that these drugs are normally metabolized by acetylation. and cardiovascular functions are adequate. people heavier than average need larger doses. raising the number of barbiturate ions in the renal filtrate. an enzyme normally found in red blood cells and . Genetics A person’s genetic characteristics may influence drug action in several ways. for example. there is little difference in absorption. After approximately 12 years of age. In addition. and others experience unusual or exaggerated effects. older adults are more likely to have acute and chronic illnesses that require multiple drugs or long-term drug therapy. less drug is reabsorbed into the blood and more is excreted by the kidneys. several genetic variations of the cytochrome P450 drugmetabolizing system have been identified. especially premature infants. These people may experience prolonged paralysis and apnea if given succinylcholine. In general. Older infants (1 month to 1 year) reach approximately adult levels of protein binding and kidney function. however. some people lack the plasma pseudocholinesterase enzyme that normally inactivates succinylcholine. Theophylline. metabolism. These interindividual variations in drug response are often attributed to genetic or ethnic differences in drug pharmacokinetics or pharmacodynamics. and slow acetylators may need smaller-than-usual doses to avoid toxic effects. The ionized particles cannot pass easily through renal tubular membranes. Changes in the GI tract include decreased gastric acidity. or procainamide (an antidysrhythmic) showed no therapeutic effects. healthy children handle drugs similarly to healthy adults. a chemical conjugation process in which the drug molecule combines with an acetyl group of acetyl coenzyme A. whereas toxicity developed in other people. Specific variations may influence any of the chemical processes by which drugs are metabolized. is cleared much faster in a 7-year-old child than in a neonate or adult (18 to 65 years). because their organ systems are not fully developed. During pregnancy. a few studies have been done with particular drugs. Drug distribution. in plasma.CHAPTER 2 BASIC CONCEPTS AND PROCESSES 19 bonate alkalinizes the urine. Impaired kidney and liver function greatly increase the risks of adverse drug effects. have a longer action. a potent muscle relaxant used in some surgical procedures. and decreased tubular secretion of drugs. Recommended doses for many drugs are listed in terms of grams or milligrams per kilogram of body weight. and are more likely to accumulate with chronic administration. Other people are deficient in glucose-6-phosphate dehydrogenase. Drugs are given to elicit certain responses that are relatively predictable for most drug recipients. In older adults (65 years and older). Fetuses have no effective mechanisms for metabolizing or eliminating drugs because their liver and kidney functions are immature. In addition. metabolism. Body Weight Body weight affects drug action mainly in relation to dose.

Adverse effects may produce es- . They also influence compliance or the willingness to carry out the prescribed drug regimen. Tolerance to pharmacologically related drugs is called cross-tolerance. and lower doses during the rest of the menstrual cycle. recipients often report both therapeutic and adverse effects from placebos. alcohol. an antianxiety agent. propranolol. angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking drugs are less effective as single-drug therapy. Gender Except during pregnancy and lactation. an antipsychotic). including the risks to a fetus if a woman becomes pregnant and the greater complexity in sample size and data analysis. phenytoin. gender has been considered a minor influence on drug action. For example. and migraine experience increased symptoms premenstrually. a significant percentage of women with arthritis. for example. and migraine. However. may need higher doses of antidepressant medications premenstrually. all pharmacokinetic processes are decreased in cardiovascular disorders characterized by decreased blood flow to tissues. and haloperidol. Women with clinical depression. sulfonamides.20 SECTION 1 INTRODUCTION TO DRUG THERAPY other body tissues. Psychological Considerations Psychological considerations influence individual responses to drug administration. and antidepressants. A placebo is a pharmacologically inactive substance. In addition. altered responses have been demonstrated in some women taking clonidine. depression. Pathologic Conditions Pathologic conditions may alter pharmacokinetic processes (Table 2–1). women are likely to have adverse drug reactions. Tolerance and cross-tolerance are usually attributed to activation of drug-metabolizing enzymes in the liver. antipyretics. the absorption of oral drugs is decreased with various GI disorders. Distribution is altered in liver or kidney disease and other conditions that alter plasma proteins. an antihypertensive. or a placebo influence client response. as opposed to therapeutic effects. One common interethnic variation is that African Americans are less responsive to some antihypertensive drugs than are white people. Most research studies related to drugs have involved men. including toxicity. Although this area has received little attention in research studies and clinical practice. Metabolism is decreased in malnutrition (eg. These people may have hemolytic anemia when given antimalarial drugs. If the person is then given sedative-type drugs or a general anesthetic. If given the higher doses required by men. including beta blockers and several psychotropic drugs (eg. a beta-adrenergic blocking drug used in the management of hypertension. Some documented interethnic variations are included in later chapters. especially opioid analgesics. In general. analgesics. In general. Several reasons have been advanced for excluding women from clinical drug trials. especially with long-term drug therapy. Interestingly. Another example is that women with schizophrenia require lower dosages of antipsychotic medications than men. a person who regularly drinks large amounts of alcohol becomes able to ingest even larger amounts before becoming intoxicated—this is tolerance to alcohol. and clinicians have extrapolated the findings to women. it may be increased in conditions that generally increase body metabolism. lithium. when given to other ethnic groups. Tolerance may be acquired to the pharmacologic action of many drugs. a particular drug. AfricanAmerican hypertensive clients respond better to diuretics or calcium channel blockers than to ACE inhibitors and beta blockers. although specific mechanisms are unknown. Ethnicity Most drug information has been derived from clinical drug trials using white men. Interethnic variations became evident when drugs and dosages developed for white people produced unexpected responses. Attitudes and expectations related to drugs in general. TOLERANCE AND CROSS-TOLERANCE Drug tolerance occurs when the body becomes accustomed to a particular drug over time so that larger doses must be given to produce the same effects. such as hyperthyroidism and fever. Placebos are used in clinical drug trials to compare the medication being tested with a “dummy” medication. For example. They also are attributed to decreased sensitivity or numbers of receptor sites. a mood-stabilizing agent. and other CNS depressants. angina pectoris. an anticonvulsant. An example is the placebo response. Most drugs produce a mixture of therapeutic and adverse effects. because differences between men and women in responses to drug therapy are being identified. which are desired responses. alprazolam. few subjects of other ethnic groups are included. ADVERSE EFFECTS OF DRUGS As used in this book. such as heart failure. which accelerates drug metabolism and excretion. larger-than-usual doses are required to produce a pharmacologic effect—this is cross-tolerance. epilepsy. Excretion is decreased in kidney disease. The increased symptoms may indicate a need for adjustments in their drug therapy regimens. all drugs can produce adverse effects. diabetes mellitus. inadequate protein to synthesize drugmetabolizing enzymes) and severe liver disease. asthma. the term adverse effects refers to any undesired responses to drug administration. and other drugs. the need to include women in drug studies is evident. if symptoms exacerbate. Another interethnic variation is that Asians usually require much smaller doses of some commonly used drugs. Some gender-related differences in responses to drugs may stem from hormonal fluctuations in women during the menstrual cycle. In addition.

where metabolism occurs. Decreased adrenal function causes hypotension and shock. less to kidneys. but faster metabolism and excretion may shorten duration of action. drugs that depress or stimulate brain function) Gastrointestinal (GI) disorders that interfere with GI function or blood flow (eg. Thus. Those who are able to take oral drugs may experience impaired absorption because of: Vomiting or diarrhea. and plasma protein binding. oral drugs are distributed directly into the systemic circulation rather than going through the portal circulation and the liver first. Absorption of oral drugs may be decreased in cirrhosis because of edema in the GI tract. and increasing blood volume. the rate of drug metabolism also returns to normal. As a thyroid disorder is treated and thyroid function returns to normal. and the duration of action may be shorter because the drug is metabolized and excreted more quickly. Metabolism and excretion are impaired because of decreased blood flow to the liver and kidneys. Distribution may be altered by changes in plasma proteins. Stress also changes plasma protein levels. or impair blood flow to body tissues (eg. Hyperthyroidism accelerates metabolism. cerebral irritation may occur with head injuries and lead to stimulation of the sympathetic nervous system and increased cardiac output. brain ischemia from inadequate cerebral blood flow. Decreased hepatic blood flow slows metabolism. abdominal infection. increased amounts of circulating catecholamines and cortisol) affects drug action by increasing cardiac output. serum bilirubin) that can displace drugs from protein-binding sites. peak blood levels may be higher and cause adverse effects. Also. hepatic enzyme activity. Severe liver disease or cirrhosis may impair all pharmacokinetic processes. decrease cardiac output. producing a shorter duration of action and a faster elimination rate. Pathologic Conditions Cardiovascular disorders that impair the pumping ability of the heart. Most drugs are eliminated from the body by hepatic metabolism. as described previously. The impaired liver may be unable to synthesize adequate amounts of plasma proteins. Hypothyroidism slows metabolism. propranolol) must be given in reduced doses to prevent high blood levels and toxicity. intramuscular. an impaired liver may not be able to synthesize adequate amounts of drug-metabolizing enzymes. histamine-2 blockers. liver impairment leads to inadequate metabolism and accumulation of substances (eg. especially albumin. Hepatic metabolism depends on hepatic blood flow. Increased blood flow may accelerate all pharmacokinetic processes. Increased hepatic blood flow increases delivery of drug molecules to hepatocytes. CNS impairment may alter pharmacokinetics indirectly by causing hypo. pancreatitis) Inflammatory bowel disorders (eg. dosages of drugs that are extensively metabolized need adjustments according to the level of thyroid function. ulcerative colitis) Endocrine disorders that impair function or change hormonal balance Diabetes-induced cardiovascular disorders Thyroid disorders Adrenal disorders resulting from the underlying illness or the stress response that accompanies illness Hepatic disorders that impair hepatic function and blood flow (eg. Also. (continued ) . Thus. With decreased protein binding. liver. Crushing tablets or opening capsules to give a drug through a GI tube. As a result. Crohn’s disease. It may be increased because GI hypermotility rapidly delivers drug molecules to sites of absorption in the small intestine and the drugs tend to be absorbed more rapidly from inflamed tissue. subcutaneous. and topical drugs is erratic because of decreased blood flow to sites of drug administration. heart failure. many patients cannot take oral medications. and shock) Central nervous system (CNS) disorders that alter respiration or circulation (eg. and GI tract). brain trauma or injury. hepatitis. which impairs all pharmacokinetic processes. Concurrent administration of foods or tube feeding solutions that decrease drug absorption. onset of drug action may be faster. The main effect is on metabolism. This shunting of blood around the liver means that oral drugs that are normally extensively metabolized during their first pass through the liver (eg. In addition. Distribution is impaired because of decreased blood flow to body tissues and thus to sites of drug action. drug action may be more rapid. trauma or surgery of the GI tract. Absorption of oral drugs is variable. Increased adrenal function (ie. which prolongs drug action and slows elimination from the body.or hyperventilation and acid–base imbalances. It may be decreased because hypermotility and diarrhea may move the drug through the GI tract too rapidly to be adequately absorbed. With faster absorption and distribution. the serum concentration of active drug is increased and the drug is distributed to sites of action and elimination more rapidly.CHAPTER 2 BASIC CONCEPTS AND PROCESSES 21 TABLE 2–1 Effects of Pathologic Conditions on Drug Pharmacokinetics Pharmacokinetic Consequences Absorption of oral. With cirrhosis. which can affect the unbound portion of a drug dose. Symptoms of impaired GI function commonly occur with both GI and non-GI disorders. renal excretion or both. cirrhosis) Impaired circulation may decrease all pharmacokinetic processes. antacids. Metabolism may be impaired by hepatic and nonhepatic disorders that reduce hepatic blood flow. paralytic ileus. causing fluid retention. Concurrent administration of drugs that raise the pH of gastric fluids (eg. redistributing cardiac output (more blood flow to the heart and brain. hypotension. and thereby accelerates drug metabolism. proton pump inhibitors). acute myocardial infarction.




Effects of Pathologic Conditions on Drug Pharmacokinetics (continued )
Pharmacokinetic Consequences Excretion may be increased when protein binding is impaired because larger amounts of free drug are circulating in the bloodstream and being delivered more rapidly to sites of metabolism and excretion. The result is a shorter drug half-life and duration of action. Excretion is decreased when the liver is unable to metabolize lipid-soluble drugs into water-soluble metabolites that can be excreted by the kidneys. ARF and CRF can interfere with all pharmacokinetic processes. Absorption of oral drugs may be decreased indirectly by changes that often occur with renal failure (eg, delayed gastric emptying, changes in gastric pH, GI symptoms such as vomiting and diarrhea). Also, in the presence of generalized edema, edema of the GI tract may impair absorption. In CRF, gastric pH may be increased by administration of oral alkalinizing agents (eg, sodium bicarbonate, citrate) and the use of antacids for phosphate-binding effects. This may decrease absorption of oral drugs that require an acidic environment for dissolution and absorption and increase absorption of drugs that are absorbed from a more alkaline environment. Distribution of many drugs may be altered by changes in extracellular fluid volume (ECF), plasma protein binding, and tissue binding. Water-soluble drugs are distributed throughout the ECF, including edema fluid, which is usually increased in renal impairment because the kidney’s ability to eliminate water and sodium is impaired. Drug binding with albumin, the main drug-binding plasma protein for acidic drugs, is usually decreased with renal impairment. Protein binding may be decreased because of less albumin or decreased binding capacity of albumin for a drug. Reasons for decreased albumin include hypermetabolic states (eg, stress, trauma, sepsis) in which protein breakdown exceeds protein synthesis, nephrotic states in which albumin is lost in the urine, and liver disease that decreases hepatic synthesis of albumin. Reasons for reduced binding capacity include structural changes in the albumin molecule or uremic toxins that compete with drugs for binding sites. When less drug is bound to albumin, the higher serum drug levels of unbound or active drug can result in drug toxicity. In addition, more unbound drug is available for distribution into tissues and sites of metabolism and excretion so that faster elimination can decrease drug half-life and therapeutic effects. For basic drugs (eg, clindamycin, propafenone), alpha1-acid glycoprotein (AAG) is the main binding protein. The amount of AAG increases in some patients, including those with renal transplants and those receiving hemodialysis. If these patients are given a basic drug, a larger amount is bound and a smaller amount is free to exert a pharmacologic effect. Finally, some conditions that often occur in renal impairment (eg, metabolic acidosis, respiratory alkalosis, others) may alter tissue distribution of some drugs. For example, digoxin can be displaced from tissue-binding sites by metabolic products that cannot be adequately excreted by impaired kidneys. Metabolism can be increased, decreased, or unaffected by renal impairment. One factor is alteration of drug metabolism in the liver. In uremia, reduction and hydrolysis reactions may be slower, but oxidation by cytochrome P450 enzymes and conjugation with glucuronide or sulfate usually proceed at normal rates. Another factor is the inability of impaired kidneys to eliminate drugs and pharmacologically active metabolites, which may lead to accumulation and adverse drug reactions with long-term drug therapy. Metabolites may have pharmacologic activity similar to or different from that of the parent drug. A third factor may be impaired renal metabolism of drugs. Although the role of the kidneys in excretion of drugs and drug metabolites is well known, their role in drug metabolism has received little attention. The kidney itself contains many of the same metabolizing enzymes found in the liver, including renal cytochrome P450 enzymes, which metabolize a variety of chemicals and drugs. Excretion of many drugs and metabolites is reduced by renal impairment. The kidneys normally excrete both the parent drug and metabolites produced by the liver and other tissues. Processes of renal excretion include glomerular filtration, tubular secretion, and tubular reabsorption, all of which may be affected by renal impairment. If the kidneys are unable to excrete drugs and metabolites, some of which may be pharmacologically active, these substances may accumulate and cause adverse or toxic effects. Respiratory impairment may indirectly affect drug metabolism. For example, hypoxemia leads to decreased enzyme production in the liver, decreased efficiency of the enzymes that are produced, and decreased oxygen available for drug biotransformation. Mechanical ventilation leads to decreased blood flow to the liver.

Pathologic Conditions

Renal impairment—acute renal failure (ARF) and chronic renal failure (CRF)

Respiratory impairments




Effects of Pathologic Conditions on Drug Pharmacokinetics (continued )
Pharmacokinetic Consequences Sepsis may affect all pharmacokinetic processes. Early sepsis is characterized by hyperdynamic circulation, with increased cardiac output and shunting of blood to vital organs. As a result, absorption, distribution, metabolism, and excretion may be accelerated. Late sepsis is characterized by hypodynamic circulation, with diminished cardiac output and reduced blood flow to major organs. Thus, absorption, distribution, metabolism, and excretion may be impaired. Shock may inhibit all pharmacokinetic processes. Absorption is impaired by decreased blood flow to sites of drug administration. Distribution is impaired by decreased blood flow to all body tissues. Metabolism is impaired by decreased blood flow to the liver. Excretion is impaired by decreased blood flow to the kidneys.

Pathologic Conditions Sepsis-induced alterations in cardiovascular function and hepatic blood flow

Shock-induced alterations in cardiovascular function and blood flow

sentially any sign, symptom, or disease process and may involve any body system or tissue. They may be common or rare, mild or severe, localized or widespread, depending on the drug and the recipient. Some adverse effects occur with usual therapeutic doses of drugs (often called side effects); others are more likely to occur and to be more severe with high doses. Common or serious adverse effects include the following: 1. CNS effects may result from CNS stimulation (eg, agitation, confusion, delirium, disorientation, hallucinations, psychosis, seizures) or CNS depression (dizziness, drowsiness, impaired level of consciousness, sedation, coma, impaired respiration and circulation). CNS effects may occur with many drugs, including most therapeutic groups, substances of abuse, and over-the-counter preparations. 2. Gastrointestinal effects (anorexia, nausea, vomiting, constipation, diarrhea) are among the most common adverse reactions to drugs. Nausea and vomiting occur with many drugs from local irritation of the gastrointestinal tract or stimulation of the vomiting center in the brain. Diarrhea occurs with drugs that cause local irritation or increase peristalsis. More serious effects include bleeding or ulceration (most often with aspirin and nonsteroidal anti-inflammatory agents) and severe diarrhea/colitis (most often with antibiotics). 3. Hematologic effects (blood coagulation disorders, bleeding disorders, bone marrow depression, anemias, leukopenia, agranulocytosis, thrombocytopenia) are relatively common and potentially life threatening. Excessive bleeding is most often associated with anticoagulants and thrombolytics; bone marrow depression is usually associated with antineoplastic drugs. 4. Hepatotoxicity (hepatitis, liver dysfunction or failure, biliary tract inflammation or obstruction) is potentially life threatening. Because most drugs are metabolized by the liver, the liver is especially susceptible to druginduced injury. Drugs that are hepatotoxic include acetaminophen (Tylenol), isoniazid (INH), methotrexate (Mexate), phenytoin (Dilantin), and aspirin and other salicylates. In the presence of drug- or disease-induced liver damage, the metabolism of many drugs is impaired. Consequently, drugs metabolized by the liver

tend to accumulate in the body and cause adverse effects. Besides hepatotoxicity, many drugs produce abnormal values in liver function tests without producing clinical signs of liver dysfunction. 5. Nephrotoxicity (nephritis, renal insufficiency or failure) occurs with several antimicrobial agents (eg, gentamicin and other aminoglycosides), nonsteroidal antiinflammatory agents (eg, ibuprofen and related drugs), and others. It is potentially serious because it may interfere with drug excretion, thereby causing drug accumulation and increased adverse effects. 6. Hypersensitivity or allergy may occur with almost any drug in susceptible clients. It is largely unpredictable and unrelated to dose. It occurs in those who have previously been exposed to the drug or a similar substance (antigen) and who have developed antibodies. When readministered, the drug reacts with the antibodies to cause cell damage and the release of histamine and other intracellular substances. These substances produce reactions ranging from mild skin rashes to anaphylactic shock. Anaphylactic shock is a lifethreatening hypersensitivity reaction characterized by respiratory distress and cardiovascular collapse. It occurs within a few minutes after drug administration and requires emergency treatment with epinephrine. Some allergic reactions (eg, serum sickness) occur 1 to 2 weeks after the drug is given. 7. Drug fever is a fever associated with administration of a medication. Drugs can cause fever by several mechanisms, including allergic reactions, damaging body tissues, increasing body heat or interfering with its dissipation, or acting on the temperatureregulating center in the brain. The most common mechanism is an allergic reaction. Fever may occur alone or with other allergic manifestations (eg, skin rash, hives, joint and muscle pain, enlarged lymph glands, eosinophilia) and its pattern may be low grade and continuous or spiking and intermittent. It may begin within hours after the first dose if the client has taken the drug before, or within approximately 10 days of continued administration if the drug is new to the client. If the causative drug is discontinued, fever usually subsides within 48 to 72 hours unless







drug excretion is delayed or significant tissue damage has occurred (eg, hepatitis). Many drugs have been implicated as causes of drug fever, including most antimicrobials, several cardiovascular agents (eg, beta blockers, hydralazine, methyldopa, procainamide, quinidine), drugs with anticholinergic properties (eg, atropine, some antihistamines, phenothiazine antipsychotic agents, and tricyclic antidepressants), and some anticonvulsants. Idiosyncrasy refers to an unexpected reaction to a drug that occurs the first time it is given. These reactions are usually attributed to genetic characteristics that alter the person’s drug-metabolizing enzymes. Drug dependence (see Chap. 15) may occur with mind-altering drugs, such as opioid analgesics, sedative-hypnotic agents, antianxiety agents, and CNS stimulants. Dependence may be physiologic or psychological. Physiologic dependence produces unpleasant physical symptoms when the dose is reduced or the drug is withdrawn. Psychological dependence leads to excessive preoccupation with drugs and drugseeking behavior. Carcinogenicity is the ability of a substance to cause cancer. Several drugs are carcinogens, including some hormones and anticancer drugs. Carcinogenicity apparently results from drug-induced alterations in cellular DNA. Teratogenicity is the ability of a substance to cause abnormal fetal development when taken by pregnant women. Drug groups considered teratogenic include analgesics, diuretics, antiepileptic drugs, antihistamines, antibiotics, antiemetics, and others.

must have a high index of suspicion so that toxicity can be rapidly recognized and treated.

Drug Overdose: General Management
Most poisoned or overdosed clients are treated in emergency rooms and discharged to their homes. A few are admitted to intensive care units (ICUs), often because of unconsciousness and the need for endotracheal intubation and mechanical ventilation. Unconsciousness is a major toxic effect of several commonly ingested substances such as benzodiazepine antianxiety and sedative agents, tricyclic antidepressants, ethanol, and opiates. Serious cardiovascular effects (eg, cardiac arrest, dysrhythmias, circulatory impairment) are also common and warrant admission to an ICU. The main goals of treatment for a poisoned patient are supporting and stabilizing vital functions (ie, airway, breathing, circulation), preventing further damage from the toxic agent by reducing additional absorption or increasing elimination, and administering specific antidotes when available and indicated. General aspects of care are described below; selected antidotes are listed in Table 2–2; and specific aspects of care are described in relevant chapters. 1. For patient who are seriously ill on first contact, enlist help for more rapid assessment and treatment. In general, starting treatment as soon as possible after drug ingestion leads to better patient outcomes. 2. The first priority is support of vital functions, as indicated by a rapid assessment of the patient’s condition (eg, vital signs, level of consciousness). In serious poisonings, an electrocardiogram is indicated and findings of severe toxicity (eg, dysrhythmias, ischemia) justify more aggressive and invasive care. Standard cardiopulmonary resuscitation (CPR) measures may be needed to maintain breathing and circulation. An intravenous (IV) line is usually needed to administer fluids and drugs, and invasive treatment or monitoring devices may be inserted. Endotracheal intubation and mechanical ventilation are often required to maintain breathing (in unconscious patients), correct hypoxemia, and protect the airway. Hypoxemia must be corrected quickly to avoid brain injury, myocardial ischemia, and cardiac dysrhythmias. Ventilation with positive end expiratory pressure (PEEP) should be used cautiously in hypotensive patients because it decreases venous return to the heart and worsens hypotension. Serious cardiovascular manifestations often require pharmacologic treatment. Hypotension and hypoperfusion may be treated with inotropic and vasopresssor drugs. Dysrhythmias are treated according to Advanced Cardiac Life Support (ACLS) protocols. Recurring seizures or status epilepticus require treatment with anticonvulsant drugs. 3. For unconscious patients, as soon as an IV line is established, some authorities recommend a dose of naloxone (2 mg IV) for possible narcotic overdose

Toxic Effects of Drugs
Drug toxicity (also called poisoning, overdose, or intoxication) results from excessive amounts of a drug and may cause reversible or irreversible damage to body tissues. It is a common problem in both adult and pediatric populations. It may result from a single large dose or prolonged ingestion of smaller doses. It may involve alcohol or prescription, over-the-counter, or illicit drugs. Poisoned patients may be seen in essentially any setting (e.g., inpatient hospital units, patients’ homes, long-term care facilities), but are especially likely to be encountered in hospital emergency departments. In some cases, the patient or someone accompanying the patient may know the toxic agent (eg, accidental overdose of a therapeutic drug, use of an illicit drug, a suicide attempt). Often, however, multiple drugs have been ingested, the causative drug or drugs are unknown, and the circumstances may involve traumatic injury or impaired mental status that make the patient unable to provide useful information. Clinical manifestations are often nonspecific for drug overdoses and may indicate other disease processes. Because of the variable presentation of drug intoxication, health care providers




Antidotes for Overdoses of Selected Therapeutic Drugs
Antidote Acetylcysteine (Mucomyst) Route and Dosage Ranges PO 140 mg/kg initially, then 70 mg/kg q4h for 17 doses IV, IM 2 mg. Give IV slowly, over at least 2 min. IV 0.2 mg over 30 sec; if no response, may give 0.3 mg. Additional doses of 0.5 mg may be given at 1-min intervals up to a total amount of 3 mg IV 50–150 mcg/kg (5–10 mg for adults) over 1 min initially, then 2–5 mg/h by continuous infusion as needed IV 1 g over 5 min; may be repeated Adults: IV 2 mg, repeated as needed Children: IV 0.05 mg/kg, up to 2 mg IV 40 mg (1 vial) for each 0.6 mg of digoxin ingested. Reconstitute each vial with 4 mL Water for Injection, then dilute with sterile isotonic saline to a convenient volume and give over 30 min, through a 0.22-micron filter. If cardiac arrest seems imminent, may give the dose as a bolus injection. IV 1 mg/100 units of heparin, slowly, over at least 10 min. A single dose should not exceed 50 mg. IM 1 g q8h PRN IV 15 mg/kg/h if hypotensive Comments Dilute 20% solution to a 5% solution with a cola or other soft drink for oral administration Infrequently used because of its toxicity Should not be given to patients with overdose of unknown drugs or drugs known to cause seizures in overdose (eg, cocaine, lithium) Glucagon increases myocardial contractility; not FDA-approved for this indication Increases myocardial contractility If poisoning is due to organophosphates (eg, insecticides), pralidoxime may be given with the atropine Recommended for severe toxicity; reverses cardiac and extracardiac symptoms in a few minutes Note: Serum digoxin levels increase after antidote administration, but the drug is bound and therefore inactive.

Overdosed Drug (Poison) Acetaminophen (see Chap. 7)

Anticholinergics (atropine; see Chap. 21) Benzodiazepines (see Chap. 8)

Physostigmine Flumazenil

Beta blockers (see Chap. 19)


Calcium channel blockers (see Chaps. 53, 55) Cholinergics (see Chap. 20)

Calcium gluconate 10% Atropine

Digoxin (see Chap. 51)

Digoxin immune fab (Digibind)

Heparin (see Chap. 57)

Protamine sulfate

Iron (see Chap. 32)


Isoniazid (INH)


Lead Opioid analgesics (Chap. 6) Phenothiazine antipsychotic agents (see Chap. 9) Thrombolytics (see Chap. 57)

Succimer Naloxone (Narcan) Diphenhydramine (Benadryl)

Aminocaproic acid (Amicar)

IV 1 g per gram of INH ingested, at rate of 1 g q2–3 min. If amount of INH unknown, give 5 g; may be repeated. Children: PO 10 mg/kg q8h for 5 days Adults: IV 0.4–2 mg PRN Children: IV 0.1 mg/kg per dose Adults: IV 50 mg Children: IV 1–2 mg/kg, up to a total of 50 mg PO, IV infusion, 5 g initially, then 1–1.25 g/h for 8 h or until bleeding is controlled. Maximum dose, 30 g/24h

Indicated for serum iron levels >500 mg/dL or serum levels >350 mg/dL with GI or cardiovascular symptoms Can bind and remove a portion of an ingested dose; urine becomes red as iron is excreted Indicated for management of seizures and correction of acidosis

Can also be given IM, SC, or by endotracheal tube Given to relieve extrapyramidal symptoms (movement disorders)

(continued )




Antidotes for Overdoses of Selected Therapeutic Drugs (continued)
Antidote Sodium bicarbonate Route and Dosage Ranges IV 1–2 mEq/kg initially, then continuous IV drip to maintain serum pH of 7.5 PO 5–10 mg daily IV (severe overdose) continuous infusion at rate no faster than 1 mg/min Comments To treat cardiac dysrhythmias, conduction disturbances, and hypotension

Overdosed Drug (Poison) Tricyclic antidepressants (see Chap. 10) Warfarin (see Chap. 57)

Vitamin K1

and thiamine (100 mg IV) for possible brain dysfunction due to thiamine deficiency. In addition, a fingerstick blood glucose test should be done and, if hypoglycemia is indicated, 50% dextrose (50 ml IV) should be given. 4. Once the patient is out of immediate danger, a thorough physical examination and efforts to determine the drug(s), the amounts, and the time lapse since exposure are needed. If the patient is unable to supply needed information, interview anyone else who may be able to do so. Ask about the use of prescription, over-the-counter, alcohol, and illicit substances. 5. There are no standard laboratory tests for poisoned patients. The client’s condition and the clinician’s judgment determine which laboratory tests are needed, although baseline tests of liver and kidney function are usually indicated. Specimens of blood, urine, or gastric fluids may be obtained for laboratory analysis. Screening tests for toxic substances are not very helpful because test results may be delayed, many substances are not detected, and the results rarely affect initial treatment. Initial treatment should never be delayed to obtain results of a toxicology screen. Identification of an unknown drug or poison is often based on the patient’s history and signs and symptoms, with specific tests as confirmation. Serum drug levels are needed when acetaminophen, alcohol, digoxin, lithium, aspirin, or theophylline is known to be an ingested drug, to assist with treatment. 6. For orally ingested drugs, gastrointestinal (GI) decontamination has become a controversial topic. For many years, standard techniques for removing drugs from the GI tract included ipecac syrup for alert patients, to induce emesis; gastric lavage for patients with decreased levels of consciousness; activated charcoal to adsorb the ingested drug in the GI tract; and a cathartic (usually 70% sorbitol) to accelerate elimination of the adsorbed drug. More recently, whole bowel irrigation (WBI) was introduced as an additional technique. Currently, there are differences of opinion regarding whether and when these techniques are indicated. These differences led to the convening of a consensus group of toxicologists from the American Academy of Clinical Toxicology (AACT) and the European

Association of Poison Centres and Clinical Toxicologists (EAPCCT). This group issued treatment guidelines that have also been endorsed by other toxicology organizations. Generally, the recommendations state that none of the aforementioned techniques should be used routinely and that adequate data to support or exclude their use are often lacking. Opinions expressed by the consensus group and others are described below: Ipecac. Usage in hospital settings has declined. Its use may delay administration or reduce effectiveness of activated charcoal, oral antidotes, and whole bowel irrigation. It is contraindicated in patients who are less than fully alert (because of the danger of aspiration). Ipecac may be used to treat mild poisonings in the home, especially in children. Parents should call a poison control center or a health care provider before giving ipecac. If used, it is most beneficial if administered within an hour after ingestion of a toxic drug dose. Gastric lavage. Its usefulness is being increasingly questioned. It is contraindicated in less than alert patients unless the patient has an endotracheal tube in place (to prevent aspiration). It may be beneficial in serious overdoses if performed within an hour of drug ingestion. If the ingested agent delays gastric emptying (eg, tricyclic antidepressants and other drugs with anticholinergic effects), the time limit may be extended. When used after ingestion of pills or capsules, the tube lumen should be large enough to allow removal of pill fragments. Activated charcoal. Sometimes called the universal antidote, it is useful in many poisoning situations. It is being used alone for mild or moderate overdoses and with gastric lavage in serious poisonings. It effectively adsorbs many toxins and rarely causes complications. It is most beneficial when given within an hour of ingestion of a potentially toxic amount of a drug known to bind to charcoal. Its effectiveness decreases with time and there are inadequate data to support or exclude its use later than 1 hour after ingestion. Activated charcoal is usually mixed in water (about 50 g or 10 heaping tablespoons in 8 oz. water) to make a slurry, which is gritty and unpleasant to



swallow. It is often given by GI tube. The charcoal blackens later bowel movements. Adverse effects include pulmonary aspiration and impaction of the charcoal–drug complex. If used with whole bowel irrigation, activated charcoal should be given before the WBI solution is started. If given during WBI, the binding capacity of the charcoal is decreased. Cathartic. It is not recommended alone and its use with activated charcoal has produced conflicting data. If used, it should be limited to a single dose to minimize adverse effects. Whole bowel irrigation (WBI). This technique is most useful for removing toxic ingestions of long-acting, sustained-release drugs (eg, many beta blockers, calcium channel blockers, and theophylline preparations); enteric coated drugs; and toxins that do not bind well with activated charcoal (eg, iron, lithium, lead). It may also be helpful in removing packets of illicit drugs, such as cocaine or heroin. When given, polyethylene glycol solution (eg, Colyte) 1–2 liters/ hour to a total of 10 liters is recommended. WBI is contraindicated in patients with serious bowel disorders (eg, obstruction, perforation, ileus), hemodynamic instability, or respiratory impairment (unless intubated). 7. Urinary elimination of some drugs and toxic metabolites can be accelerated by changing the pH of urine (eg, acidifying with amphetamine overdose; alkalinizing with salicylate overdose), diuresis, or hemodialysis. Hemodialysis is the treatment of choice in severe lithium and aspirin (salicylate) poisoning. 8. Administer specific antidotes when available and indicated by the client’s clinical condition. Available antidotes vary widely in effectiveness. Some are very effective and rapidly reverse toxic manifestations (eg, naloxone for opiates, flumazenil for benzodiazepines, specific Fab fragments for digoxin). Others are less effective (eg, deferoxamine for acute iron ingestion) or potentially toxic themselves (eg, physostigmine for tricyclic antidepressant overdose). When an antidote is used, its half-life relative to the toxin’s half-life must be considered. For example, the half-life of naloxone, a narcotic antagonist, is relatively short compared with the half-life of the longer-acting opiates such as methadone. Similarly, flumazenil has a

How Can You Avoid This Medication Error?
Answer: Grapefruit juice interacts with many medications, including felodipine. The drug level of felodipine increases because the grapefruit juice inhibits the isozyme of cytochrome P450, which is important in the metabolism of felodipine. As the blood level increases, serious toxic effects can occur. Other juices do not impact cytochrome P450 so it would be safe to have Mrs. Beecher take her medication with another type of juice or water. Notify the physician regarding Mrs. Beecher’s hypotension and the drug–food interaction. If Mrs. Beecher remains on felodipine, she must be cautioned to eliminate grapefruit juice from her diet.

shorter half-life than most benzodiazepines. Thus, repeated doses of these agents may be needed to prevent recurrence of the toxic state.

Review and Application Exercises
1. Why do nurses need to understand cellular physiology in relation to drug therapy? 2. What are some factors that decrease absorption of an oral drug? 3. Drug dosage is a major determinant of both therapeutic and adverse drug effects. How can you use this knowledge in monitoring a client’s response to drug therapy? 4. Does protein binding speed or slow drug distribution to sites of action? 5. Are drugs equally distributed throughout the body? Why or why not? 6. What are the implications of hepatic enzyme induction and inhibition in terms of drug metabolism and elimination from the body? 7. For a drug in which biotransformation produces active metabolites, is drug action shortened or lengthened? What difference does this make in client care? 8. Which pharmacokinetic processes are likely to be impaired with severe cardiovascular disease and with severe renal disease? 9. What are the main elements of the receptor theory of drug action? 10. When drug–drug interactions occur, are drug actions increased or decreased? 11. What are some reasons for individual differences in responses to drugs? SELECTED REFERENCES
Barone, J. A. & Hermes-DeSantis, E. R. (2000). Adverse drug reactions and drug-induced diseases. In E. T. Herfindal & D. R. Gourley (Eds.), Textbook of therapeutics: Drug and disease management, 7th ed., pp. 21–34. Philadelphia: Lippincott Williams & Wilkins.

Nursing Notes: Apply Your Knowledge
Answer: Half-life is the time required for the serum concentration of a drug to decrease by 50%. After 1 hour, the serum concentration would be 50 units/mL (100/2). After 2 hours, the serum concentration would be 25 units/mL (50/2) and reach the nontoxic range.



Brater, D. C. (2000). Principles of clinical pharmacology. In H. D. Humes (Ed.), Kelley’s Textbook of internal medicine, 4th ed., pp. 311–319. Philadelphia: Lippincott Williams & Wilkins. Drug facts and comparisons. (Updated monthly). St. Louis: Facts and Comparisons. Ensom, M. H. H. (2000). Gender-based differences and menstrual cyclerelated changes in specific diseases: Implications for pharmacotherapy. Pharmacotherapy, 20(5), 523–539. Guyton, A. C. & Hall, J. E. (2000). Textbook of medical physiology, 10th ed. Philadelphia: Saunders. Klein-Schwartz, W. & Oderda, G. M. (2000). Clinical toxicology. In E. T. Herfindal & D. R. Gourley (Eds.), Textbook of therapeutics: Drug and dis-

ease management, 7th ed., pp. 51–68. Philadelphia: Lippincott Williams & Wilkins. Krenzelok, E. P. & Vale, J. A. (1998, May). The AACT/EAPCCT position statements on gut decontamination in acute poisoning. Hospital Pharmacy, 33(5), 533–543. Matthews, H. W. & Johnson, J. (2000). Racial, ethnic, and gender differences in response to drugs. In E. T. Herfindal & D. R. Gourley (Eds.), Textbook of therapeutics: Drug and disease management, 7th ed., pp. 93–103. Philadelphia: Lippincott Williams & Wilkins. Tatro, D. S. (2000). Drug interactions. In E. T. Herfindal & D. R. Gourley (Eds.), Textbook of therapeutics: Drug and disease management, 7th ed., pp. 35–49. Philadelphia: Lippincott Williams & Wilkins.

chapter 3 Administering Medications

1. List the five rights of drug administration. 2. Discuss knowledge and skills needed to implement the five rights. 3. List requirements of a complete drug order or prescription. 4. Accurately interpret drug orders containing common abbreviations. 5. Differentiate drug dosage forms for various routes and purposes of administration.

6. Discuss advantages and disadvantages of oral, parenteral, and topical routes of drug administration. 7. Identify supplies, techniques, and observations needed for safe and accurate administration by different routes.

Critical Thinking Scenario Ms. Mabel Zack is transferred to your rehabilitation facility after a cerebral vascular accident (stroke) 2 weeks ago. When you review her chart, it indicates she has right-sided hemiparesis, memory deficits, and dysphagia (difficulty swallowing). Reflect on: ᮣ Outline appropriate assessments to determine if it is safe to give Ms. Zack oral medications. ᮣ If a swallowing evaluation indicates that Ms. Zack can take medications orally, what precautions can you take to help ensure her safety? ᮣ How might you individualize your teaching plan, considering Ms. Zack’s memory deficits?

rugs given for therapeutic purposes are called medications. Giving medications to clients is an important nursing responsibility in many health care settings, including ambulatory care, hospitals, long-term care facilities, and clients’ homes. The basic requirements for accurate drug administration are often called the “five rights”: giving the right drug, in the right dose, to the right client, by the right route, at the right time. These “rights” require knowledge of the drugs to be given and the clients who are to receive them as well as specific nursing skills and interventions. When one of these rights is violated, medication errors can occur. Nurses need to recognize circumstances in which errors are likely to occur and intervene to prevent errors and protect clients. This chapter is concerned with safe and accurate medication administration.


• Follow the “five rights” consistently. • Learn essential information about each drug to be given
(eg, indications for use, contraindications, therapeutic effects, adverse effects, and any specific instructions about administration). • Interpret the prescriber’s order accurately (ie, drug name, dose, frequency of administration). Question the prescriber if any information is unclear or if the drug seems inappropriate for the client’s condition. • Read labels of drug containers for the drug name and concentration (usually in mg per tablet, capsule, or milliliter of solution). Many medications are available in different dosage forms and concentrations; it is extremely important that the correct ones be used.




How Can You Avoid This Medication Error?
You are administering 6 AM medications to a client on a medical unit. You enter Mr. Gonzales’ room, gently shake him awake, and call him by name. He slowly awakens and appears groggy. You explain that you have his medications, which he takes and quickly falls back to sleep. On exiting the room, you look at the room number and realize that you just gave medications to Mr. Sanchez.

son is that children have limited sites for administration of IV drugs, and several may be given through the same site. In many cases, the need for small volumes of fluid limits flushing between drugs (which may produce undesirable interactions with other drugs and IV solutions). In 1998, the Food and Drug Administration published a requirement that new drugs likely to be important or frequently used in the treatment of children should be labeled with instructions for safe pediatric use.

• Minimize the use of abbreviations for drug names, doses,
routes of administration, and times of administration. This promotes safer administration and reduces errors. When abbreviations are used, by prescribers or others, interpret them accurately or question the writers about intended meanings. Calculate doses accurately. Current nursing practice requires few dosage calculations (most are done by pharmacists). However, when they are needed, accuracy is essential. For medications with a narrow safety margin or potentially serious adverse effects, ask a pharmacist or a colleague to do the calculation also and compare the results. This is especially important when calculating children’s dosages. Measure doses accurately. Ask a colleague to doublecheck measurements of insulin and heparin, unusual doses (ie, large or small), and any drugs to be given intravenously. Use the correct procedures and techniques for all routes of administration. For example, use appropriate anatomic landmarks to identify sites for intramuscular (IM) injections, follow the manufacturers’ instructions for preparation and administration of intravenous (IV) medications, and use sterile materials and techniques for injectable and eye medications. Seek information about the client’s medical diagnoses and condition in relation to drug administration (eg, ability to swallow oral medications; allergies or contraindications to ordered drugs; new signs or symptoms that may indicate adverse effects of administered drugs; heart, liver, or kidney disorders that may interfere with the client’s ability to eliminate drugs). Verify the identity of all clients before administering medications; check identification bands on clients who have them (eg, in hospitals or long-term facilities). Omit or delay doses as indicated by the client’s condition; report or record omissions appropriately. Be especially vigilant when giving medications to children because there is a high risk of medication errors. One reason is their great diversity, in age from birth to 18 years and weight from 2–3 kilograms (kg) to 100 kg or more. Another is that most drugs have not been tested in children. A third reason is that many drugs are marketed in dosage forms and concentrations suitable for adults. This often requires dilution, calculation, preparation, and administration of very small doses. A fourth rea-

Registered and licensed practical nurses are legally empowered, under state nurse practice acts, to give medications ordered by licensed physicians and dentists. In some states, nurse practitioners may prescribe medications. When giving medications, the nurse is legally responsible for safe and accurate administration. This means the nurse may be held liable for not giving a drug or for giving a wrong drug or a wrong dose. In addition, the nurse is expected to have sufficient drug knowledge to recognize and question erroneous orders. If, after questioning the prescriber and seeking information from other authoritative sources, the nurse considers that giving a drug is unsafe, the nurse must refuse to give the drug. The fact that a physician wrote an erroneous order does not excuse the nurse from legal liability if he or she carries out that order. The nurse also is legally responsible for actions delegated to people who are inadequately prepared for or legally barred from administering medications (such as nursing assistants). However, certified medical assistants (CMAs) administer medications in physicians’ offices and certified medication aides (nursing assistants with a short course of training, also called CMAs,) often administer medications in long-term care facilities. The nurse who consistently follows safe practices in giving medications does not need to be excessively concerned about legal liability. The basic techniques and guidelines described in this chapter are aimed at safe and accurate preparation and administration; most errors result when these practices are not followed. Legal responsibilities in other aspects of drug therapy are less tangible and clear-cut. However, in general, nurses are expected to monitor clients’ responses to drug therapy (eg, therapeutic and adverse effects) and to teach clients safe and effective self-administration of drugs when indicated. These aspects are described more fully in Chapter 4.

• • •

Increasing attention is being paid to the number and consequences of medication errors. In one study of 1116 hospitals, medication errors (a total of 430,586) were reported in approximately 5% of admitted patients. In 913 of those hospitals, over 17,000 errors (0.25% of admitted patients) re-



portedly caused adverse client outcomes (usually described as serious illness, conditions that prolong hospitalization or require additional treatment, or death). Other studies have reported that common errors include giving an incorrect dose, not giving an ordered drug, and giving an unordered drug. Specific drugs often associated with errors include insulin, heparin, and warfarin. There are several steps and numerous people involved in getting each dose of a medication to the intended client. Each step or person has a potential for contributing to a medication error (Box 3–1). All health care providers involved in drug therapy must be extremely vigilant in all phases of drug administration.

Each agency has a system for distributing drugs. The unitdose system, in which most drugs are dispensed in singledose containers for individual clients, is widely used. Drug orders are checked by a pharmacist or pharmacy technician, who then places the indicated number of doses in the client’s medication drawer at scheduled intervals. When a dose is due, the nurse removes the medication and takes it to the client. Unit-dose wrappings of oral drugs should be left in

place until the nurse is in the presence of the client and ready to give the medication. Each dose of a drug must be recorded on the client’s medication administration record (MAR) as soon as possible after administration. Increasingly, agencies are using automated, computerized, locked cabinets for which each nurse on a unit has a password or code for accessing the cabinet and obtaining a drug dose. These automated systems maintain an inventory and drugs are restocked as needed. Controlled drugs, such as opioid analgesics, are usually kept as a stock supply in a locked drawer or automated cabinet and replaced as needed. Each dose is signed for and recorded on the client’s MAR. Each nurse must comply with legal regulations and agency policies for dispensing and recording controlled drugs.

Medication orders should include the full name of the client; the generic or trade name of the drug; the dose, route, and frequency of administration; and the date, time, and signature of the prescriber, usually a physician. Most orders in a health care agency are handwritten on an order sheet in the client’s medical record or typed into a com-

BOX 3–1

age; fail to keep appointments for follow-up care; and fail to ask for information about prescription and nonprescription drugs when needed. Drugs Drugs may have similar names that can lead to erroneous prescribing, dispensing, or administration. For example, the antiseizure drug Lamictal (generic name, lamotrigine) has been confused with Lamisil, an antifungal drug, lamivudine, an antiviral drug, and others. As a result, the FDA-proposed labeling changes to make the differences more noticeable. The FDA is also looking at proposed trade names of new drugs prior to marketing, to see if they are likely to be confused with older drugs, and increasing surveillance of medication errors attributed to drug name confusion. In addition to similar names, many drugs, especially those produced by the same manufacturer, have similar packaging. This can lead to errors if container labels are not read carefully, especially if the products are shelved or stored next to each other. Long-acting oral dosage forms with various, sometimes unclear indicators (eg, LA, XL, XR), may be crushed, chewed, or otherwise broken so that the long-acting feature is destroyed. This can cause an overdose. Circumstances Prescribers, pharmacists, and nurses may have a heavy workload, with resultant rushing of prescribing, dispensing, or administering medications. They may also experience distractions by interruptions, noise, and other events in the work environment that make it difficult to pay needed attention to the medication-related task.

Medication errors may occur during any phase of drug therapy, including prescribing, dispensing, and administration. The main purpose of including potential sources of errors here is to increase the ability of health care providers to recognize risky situations and to prevent errors when possible. Health Care Providers Prescribers may write orders illegibly; order a drug that is not indicated by the client’s condition; fail to order a drug that is indicated; fail to consider the client’s age, size, kidney function, liver function, and disease process when selecting a drug or dosage; fail to consider other medications the client is taking, including prescription and over-the-counter drugs; lack sufficient knowledge about the drug; fail to monitor for, or instruct others to monitor for, effects of administered drugs; and fail to discontinue drugs appropriately. Pharmacists may not know the client’s condition or recognize an inappropriate or erroneous physician’s order. They may dispense incorrect medications, mislabel containers, or fail to ask outpatients about other drugs being taken. Nurses may have inadequate knowledge about a drug or about the client receiving the drug; not follow the “five rights”; fail to question the medication order when indicated. Clients/Consumers People may take drugs from several prescribers; fail to inform one physician about drugs prescribed by another; get prescriptions filled at more than one pharmacy; fail to get prescriptions filled or refilled; underuse or overuse an appropriately prescribed drug; take drugs left over from a previous illness or prescribed for someone else; fail to follow instructions for drug administration or stor-



puter. Occasionally, verbal or telephone orders are acceptable. These are written on the client’s order sheet, signed by the person taking the order, and later countersigned by the prescriber. Once the order is written, a copy is sent to the pharmacy, where the order is recorded and the drug is dispensed to the appropriate client care unit. In many agencies, pharmacy staff prepare a computer-generated MAR for each 24-hour period. For clients in ambulatory care settings, the procedure is essentially the same for drugs to be given immediately. For drugs to be taken at home, written prescriptions are given. In addition to the previous information, a prescription should include instructions for taking the drug (eg, dose and frequency) and whether the prescription can be refilled. Prescriptions for Schedule II controlled drugs cannot be refilled. To interpret medication orders accurately, the nurse must know commonly used abbreviations for routes, dosages, and times of drug administration (Table 3–1). If the nurse cannot read the physician’s order or if the order seems erroneous, he or she must question the order before giving the drug.

Drug preparations and dosage forms vary according to the drug’s chemical characteristics, reason for use, and route of administration. Some drugs are available in only one dosage form; others are available in several forms. Characteristics of various dosage forms are described below and in Table 3–2. Dosage forms of systemic drugs include liquids, tablets, capsules, suppositories, and transdermal and pump delivery systems. Systemic liquids are given orally (PO) or by injection. Those given by injection must be sterile. Tablets and capsules are given PO. Tablets contain active drug plus binders, colorants, preservatives, and other substances. Capsules contain active drug enclosed in a gelatin capsule. Most tablets and capsules dissolve in the acidic fluids of the stomach and are absorbed in the alkaline fluids of the upper small intestine. Enteric-coated tablets and capsules are coated with a substance that is insoluble in stomach acid. This delays dissolution until the medication reaches the intestine, usually to avoid gastric irritation or to keep the drug from being destroyed by gastric acid. Tablets for sublingual or buccal administration must be specifically formulated for such use. Several controlled-release dosage forms and drug delivery systems are available and more continue to be developed. These formulations maintain more consistent serum drug levels and allow less frequent administration, which is more convenient for clients. Oral tablets and capsules are called by a variety of names (eg, timed release, sustained release, extended release) and their names usually include SR, XL, or other indications that they are long-acting formulations. Most of these formulations are given once or twice daily. Some drugs (eg, alendronate for osteoporosis and fluoxetine for major depression) are available in formulations that deliver a full week’s dosage in one oral tablet. Because controlled-release tablets and capsules contain high amounts of drug intended to be absorbed slowly and act over a prolonged period of time, they should never be broken, opened, crushed, or chewed. Such an action allows the full dose to be absorbed immediately and constitutes an overdose, with potential organ damage or death. Transdermal (skin patch) formulations include systemically absorbed clonidine, estrogen, fentanyl, nitroglycerin, and scopolamine. These medications are slowly absorbed from the skin patches over varying periods of time (eg, 1 week for clonidine and estrogen). Pump delivery systems may be external or implanted under the skin and refillable or long acting without refills. Pumps are used to administer insulin, opioid analgesics, antineoplastics, and other drugs. Solutions, ointments, creams, and suppositories are applied topically to skin or mucous membranes. They are formulated for the intended route of administration. For example, several drugs are available in solutions for nasal or oral inhalation; they are usually self-administered as a spray into the nose or mouth. Many combination products containing fixed doses of two or more drugs are also available. Commonly used combinations include analgesics, antihypertensive drugs, and cold remedies. Most are oral tablets, capsules, or solutions.


Common Abbreviations

Routes of Drug Administration IM IV OD OS OU PO SC SL Drug Dosages intramuscular intravenous right eye* left eye* both eyes* by mouth, oral subcutaneous sublingual

cc cubic centimeter g gram gr grain gt drop† mg milligram mL milliliter oz ounce tbsp tablespoon tsp teaspoon Times of Drug Administration ac ad lib bid hs pc PRN qd q4h qid qod stat tid before meals as desired twice daily bedtime after meals when needed every day, daily every four hours four times daily every other day immediately three times daily

*Because of errors made with the abbreviations, some authorities recommend spelling out the site (eg, right eye). †drops = gtt.




Drug Dosage Forms
Characteristics Considerations/Precautions

Dosage Forms and Their Routes of Administration Tablets Regular: PO, GI tube (crushed and mixed with water) Chewable: PO Enteric coated: PO

Extended release (XL): PO

Sublingual: Under the tongue Buccal: Held in cheek Capsules Regular: PO

• Contain active drug plus binders, dyes, preservatives • Dissolve in gastric fluids Colorful and flavored, mainly for young children who are unable to swallow or who refuse regular tablets Dissolve in small intestine rather than stomach; mainly used for medications that cause gastric irritation • Also called sustained release (SR), long acting (LA), and others • Formulated for slow absorption and prolonged action • Effects of most last 12–24 hours • Contain relatively large doses of active drug • Dissolve quickly • Medication absorbed directly into the bloodstream and exerts rapid systemic effects

8 oz of water recommended when taken orally, to promote dissolution and absorption Colors and flavors appeal to children; keep out of reach to avoid accidental overdose. Do not crush; instruct clients not to chew or crush.

Warning: Crushing to give orally or through a GI tube administers an overdose, with potentially serious adverse effects or death!! Never crush; instruct clients not to chew or crush Few medications formulated for administration by these routes

Extended release (XL): PO

• Contain active drug, fillers, and preservatives in a gelatin capsule • Gelatin capsules dissolve in gastric fluid and release medication • Also called sustained release (SR), long acting (LA), and others • Formulated for slow absorption and prolonged action • Effects of most last 12–24 hours • Contain relatively large doses of active drug

As with oral tablets, 8 oz of fluid recommended to promote dissolution of capsule and absorption of medication Warning: Emptying a capsule to give the medication orally or through a GI tube administers an overdose, with potentially serious adverse effects or death!! Instruct clients not to bite, chew or empty these capsules.

Solutions Oral: PO, GI tube Parenteral: IV, IM SC, intradermal

• Absorbed rapidly because they do not need to be dissolved • Medications and all administration devices must be sterile • IV produces rapid effects; SC is used mainly for insulin and heparin; IM is used for only a few drugs; intradermal is used mainly to inject skin test material rather than therapeutic drugs.

Use of appropriate measuring devices and accurate measurement are extremely important. Use of appropriate equipment (eg, needles, syringes, IV administration sets) and accurate measurement are extremely important. Insulin syringes should always be used for insulin and tuberculin syringes are recommended for measuring small amounts of other drugs.

Suspensions PO, SC (NPH and Lente insulins) Dermatologic Creams, Lotions, Ointments Topically to skin

• These are particles of active drug suspended in a liquid; the liquid must be rotated or shaken before measuring a dose.

Drug particles settle to the bottom on standing. If not remixed, the liquid vehicle is given rather than the drug dose.

• Most are formulated for minimal absorption through skin and local effects at the site of application; medications in skin patch formulations are absorbed and exert systemic effects.

Formulations vary with intended uses and are not interchangeable. When removed from the client, skin patches must be disposed of properly to prevent someone else from being exposed to the active drug remaining in the patch. Several research studies indicate that patients often do not use MDIs correctly and sometimes are incorrectly taught by health care providers. Correct use is essential to obtaining therapeutic effects and avoiding adverse effects. Can be systemically absorbed and cause systemic adverse effects

Solutions and Powders for Oral or Nasal Inhalation, Including Metered Dose Inhalers (MDIs) Eye Solutions and Ointments

• Oral inhalations are used mainly for asthma; nasal sprays for nasal allergies (allergic rhinitis) • Effective with less systemic effect than oral drugs • Deliver a specified dose per inhalation • Should be sterile • Most are packaged in small amounts, to be used by a single patient • Used for cough and sore throat • Used mainly for ear infections

Throat Lozenges Ear Solutions

(continued )




Drug Dosage Forms (continued )
Characteristics • Formulated for insertion into the vagina • Commonly used to treat vaginal infections • Formulated for insertion into the rectum • Suppositories may be used to administer sedatives, analgesics, laxatives • Medicated enemas are used to treat inflammatory bowel diseases (eg, ulcerative colitis) Effects somewhat unpredictable because absorption is erratic Considerations/Precautions

Dosage Forms and Their Routes of Administration Vaginal Creams and Suppositories Rectal Suppositories and Enemas

PO, oral; GI, gastrointestinal; IV, intravenous; IM, intramuscular; SC, subcutaneous.

When calculating drug doses, the importance of accuracy cannot be overemphasized. Accuracy requires basic skills in mathematics, knowledge of common units of measurement, and methods of using data in performing calculations.

Systems of Measurement
The most commonly used system of measurement is the metric system, in which the meter is used for linear measure, the gram for weight, and the liter for volume. One milliliter (mL) equals 1 cubic centimeter (cc), and both equal 1 gram (g) of water. The apothecary system, now obsolete and rarely used, has units called grains, minims, drams, ounces, pounds, pints, and quarts. The household system, with units of drops, teaspoons, tablespoons, and cups, is infrequently used in health care agencies but may be used at home. Table 3–3 lists equivalent measurements within and among these systems. Equivalents are approximate. A few drugs are ordered and measured in terms of units or milliequivalents (mEq). Units express biologic activity in

animal tests (ie, the amount of drug required to produce a particular response). Units are unique for each drug. For example, concentrations of insulin and heparin are both expressed in units, but there is no relation between a unit of insulin and a unit of heparin. These drugs are usually ordered in the number of units per dose (eg, NPH insulin 30 units subcutaneously [SC] every morning, or heparin 5000 units SC q12h) and labeled in number of units per milliliter (U 100 insulin contains 100 units/mL; heparin may have 1000, 5000, or 10,000 units/mL). Milliequivalents express the ionic activity of a drug. Drugs such as potassium chloride are ordered and labeled in the number of milliequivalents per dose, tablet, or milliliter.

Mathematical Calculations
Most drug orders and labels are expressed in metric units of measurement. If the amount specified in the order is the same as that on the drug label, no calculations are required, and preparing the right dose is a simple matter. For example, if the order reads “ibuprofen 400 mg PO” and the drug label reads “ibuprofen 400 mg per tablet,” it is clear that one tablet is to be given. What happens if the order calls for a 400-mg dose and 200-mg tablets are available? The question is, “How many 200-mg tablets are needed to give a dose of 400 mg?” In this case, the answer can be readily calculated mentally to indicate two tablets. This is a simple example that also can be used to illustrate mathematical calculations. This problem can be solved by several acceptable methods; the following formula is presented because of its relative simplicity for students lacking a more familiar method. D X = H V D = desired dose (dose ordered, often in milligrams) H = on-hand or available dose (dose on the drug label, often in mg per tablet, capsule, or milliliter) X = unknown (number of tablets, in this example) V = unit (one tablet, here)


Apothecary = 15 or 16 minims = 1 fluid dram = 1 gr = 1/2 gr = 1 oz = 8 oz = 1 lb = 16 oz = 32 oz = 1 mg =1g = 2.2 lb = 10 gr Household = 15 or 16 drops = 1 tsp = 2 tbsp = 1 cup = 1 pint = 1 quart = 2.2 lb

1 mL = 1 cc 4 or 5 mL 60 or 65 mg 30 or 32 mg 30 g = 30 mL 250 mL 454 g 500 mL = 500 cc 1 L = 1000 mL 1000 mcg* 1000 mg 1000 g = 1 kg 0.6 g = 600 mg or 650 mg
*mcg = microgram.



400 mg X tablet = 200 mg 1 tablet Cross multiply: 200 X = 400 400 X= = 2 tablets 200 What happens if the order and the label are written in different units? For example, the order may read “amoxicillin 0.5 g” and the label may read “amoxicillin 500 mg/capsule.” To calculate the number of capsules needed for the dose, the first step is to convert 0.5 g to the equivalent number of milligrams, or convert 500 mg to the equivalent number of grams. The desired or ordered dose and the available or label dose must be in the same units of measurement. Using the equivalents (ie, 1 g = 1000 mg) listed in Table 3–2, an equation can be set up as follows: 1g 0.5 g = 1000 mg X mg X = 0.5 × 1000 = 500 mg The next step is to use the new information in the formula, which then becomes: D X = H V 500 mg X capsules = 500 mg 1 capsule 500 X = 500 500 X= = 1 capsule 500 The same procedure and formula can be used to calculate portions of tablets or dosages of liquids. These are illustrated in the following problems: 1. Order: 25 mg PO Label: 50-mg tablet 25 mg X tablet = 50 mg 1 tablet 50 X = 25 X= 2. Order: 25 mg IM Label: 50 mg in 1 cc 25 mg X cc = 50 mg 1 cc 50 X = 25 X= 25 = 0.5 cc 50 25 = 0.5 tablet 50

3. Order: 4 mg IV Label: 10 mg/mL 4 mg X mL = 10 mg 1 mL 10 X = 4 X= 4 = 0.4 mL 10

4. Order: Heparin 5000 units Label: Heparin 10,000 units/mL 5000 units X mL = 10, 000 units 1 mL 10, 000 X = 5000 X= 5000 = 0.5 mL 10, 000

5. Order: KCl 20 mEq Label: KCl 10 mEq/5 mL 20 mEq X mL = 10 mEq 5 mL 10 X = 100 X= 100 = 10 mL 10

Routes of administration depend on drug characteristics, client characteristics, and desired responses. The major routes are oral, parenteral, and topical. Each has advantages, disadvantages, indications for use, and specific techniques of administration (Table 3–4). The term parenteral refers to any route other than gastrointestinal (enteral), but is commonly used to indicate SC, IM, and IV injections. Injections require special drug preparations, equipment, and techniques. General characteristics are described below; specific considerations for the intravenous route are described in Box 3–2.

Drugs for Injection
Parenteral drugs must be prepared, packaged, and administered in ways to maintain sterility. Vials are closed glass or plastic containers with rubber stoppers through which a sterile needle can be inserted for withdrawing medication. Single-dose vials usually do not contain a preservative and must be discarded after a dose is withdrawn; multiple-dose vials contain a preservative and may be reused if aseptic technique is maintained. Ampules are sealed glass containers, the tops of which must be broken off to allow insertion of a needle and withdrawal of the medication. Broken ampules and any remaining medication are discarded; they are no longer sterile and




Routes of Drug Administration
Advantages • Simple and can be used by most people • Convenient; does not require complex equipment • Relatively inexpensive Disadvantages • Amount of drug acting on body cells is unknown because varying portions of a dose are absorbed and some drug is metabolized in the liver before reaching the bloodstream for circulation • Slow drug action • Irritation of gastrointestinal mucosa by some drugs • With nasogastric tubes, medications may be aspirated into the lungs • Small-bore tubes often become clogged • Requires special precautions to give correctly and avoid complications • Only a small amount of drug (up to 1 mL) can be given • Drug absorption is relatively slow • Only a few drugs can be given SC Comments The oral route should generally be used when possible, considering the client’s condition and ability to take or tolerate oral drugs.

Route and Description Oral

GI tubes (eg, nasogastric, gastrostomy)

• Allows use of GI tract in clients who cannot take oral drugs • Can be used over long periods of time, if necessary • May avoid or decrease injections

Subcutaneous (SC) injection—injection of drugs under the skin, into the underlying fatty tissue

• Relatively painless • Very small needles can be used • Insulin and heparin, commonly used medications that often require multiple daily injections, can be given SC • May be used for several drugs • Drug absorption is rapid because muscle tissue has an abundant blood supply • Allows medications to be given to a patient who cannot take fluids or drugs by GI tract • Bypasses barriers to drug absorption that occur with other routes • Rapid drug action • Larger amounts can be given than by SC and IM routes • Allows slow administration when indicated

Intramuscular (IM) injection—injection of drugs into selected muscles Intravenous (IV) injection—injection of a drug into the bloodstream

Topical administration— application to skin or mucous membranes. Application to mucous membranes includes drugs given by nasal or oral inhalation; by instillation into the lungs, eyes, or nose; and by insertion under the tongue (sublingual), into the cheek (buccal), and into the vagina or rectum.

• With application to intact skin, most medications act at the site of application, with little systemic absorption or systemic adverse effects. • Some drugs are given topically for systemic effects (eg, medicated skin patches). Effects may last several days and the patches are usually convenient for clients. • With application to mucous membranes, most drugs are well and rapidly absorbed

• A relatively small amount of drug (up to 3 mL) can be given • Risks of damage to blood vessels or nerves if needle is not positioned correctly • Time and skill required for venipuncture and maintaining an IV line • Once injected, drug cannot be retrieved if adverse effects or overdoses occur • High potential for adverse reactions from rapid drug action and possible complications of IV therapy (ie, bleeding, infection, fluid overload, extravasation) • Phlebitis commonly occurs and increases risks of thrombosis • Phlebitis and thrombosis cause discomfort or pain, may take days or weeks to subside, and limit the veins available for future therapy • Some drugs irritate skin or mucous membranes and cause itching, rash, or discomfort • With inflamed, abraded, or damaged skin, drug absorption is increased and systemic adverse effects may occur • Application to mucous membranes may cause systemic adverse effects (eg, beta blocker eye drops, used to treat glaucoma, can cause bradycardia just as oral beta blockers can) • Specific drug preparations must be used for the various routes (ie, dermatologics for skin; ophthalmics for eyes; sublingual, buccal, vaginal, and rectal preparations for those sites).

• Liquid preparations are preferred over crushed tablets and emptied capsules, when available • Tube should be rinsed before and after instilling medication The SC route is commonly used for only a few drugs because many drugs are irritating to SC tissues. Such drugs may cause pain, necrosis and abscess formation if injected SC. It is very important to use anatomic landmarks when selecting IM injection sites.

• The nurse should wear latex gloves to start IV infusions, for protection against exposure to bloodborne pathogens. • Phlebitis and thrombosis result from injury to the endothelial cells that form the inner lining (intima) of veins and may be caused by repeated venipunctures, the IV catheter, hypertonic IV fluid, or irritating drugs.

When available and effective, topical drugs are often preferred over oral or injected drugs, because of fewer and/or less severe systemic adverse effects.



BOX 3–2

lumen of the vein is recommended. This allows good blood flow and rapidly dilutes drug solutions as they enter the vein. This, in turn, prevents high drug concentrations and risks of toxicity. Also, once a catheter is inserted, it is very important to tape it securely so that it does not move around. Movement of the catheter increases venous irritation and risks of thrombophlebitis and infection. If signs of venous irritation and inflammation develop, the catheter should be removed and a new one inserted at another site. Additional recommendations include application of a topical antibiotic or antiseptic ointment at the IV site after catheter insertion, a sterile occlusive dressing over the site, and limiting the duration of placement to a few days. Many medications are administered through peripherally inserted central catheters (PICC lines) or central venous catheters, in which the catheter tips are inserted into the superior vena cava, next to the right atrium of the heart. Central venous catheters may have single, double, or triple lumens. Other products, which are especially useful for long-term IV drug therapy, include a variety of implanted ports, pumps, and reservoirs. If a catheter becomes clogged, do not irrigate it. Doing so may push a clot into the circulation and result in a pulmonary embolus, myocardial infarction, or stroke. It may also cause septicemia, if the clot is infected. Needleless systems are one of the most important advances in IV therapy. Most products have a blunt-tipped plastic insertion device and an injection port that opens. These systems greatly decrease needle-stick injuries and exposure to bloodborne pathogens. Electronic infusion devices allow amounts and flow rates of IV drug solutions to be set and controlled by a computer. Although the devices save nursing time, because the nurse does not need to count drops and continually adjust flow rates, probably the biggest advantage is the steady rate of drug administration. The devices are used in most settings where IV drugs and IV fluids are administered, but they are especially valuable in pediatrics, where very small amounts of medication and IV fluid are needed, and in intensive care units, where strong drugs and varying amounts of IV fluid are usually required. Several types of pumps are available, even within the same health care agency. It is extremely important that nurses become familiar with the devices used in their work setting, so they can program them accurately and determine whether or not they are functioning properly (ie, delivering medications as ordered). Site Selection IV needles are usually inserted into a vein on the hand or forearm; IV catheters may be inserted in a peripheral site or centrally (the catheter tip ends in the superior vena cava, near the right atrium of the heart, and medications and fluids are rapidly diluted and flow directly into the heart). In general, recommendations are: • Start at the most distal location. This conserves more proximal veins for later use, if needed. Veins on the back of the hand and on the forearm are often used. These sites usually provide more comfort and freedom of movement for clients than other sites. • Use veins with a large blood volume flowing through them when possible. Many drugs cause irritation and phlebitis in small veins. (continued )

Methods IV injection or IV push is the direct injection of a medication into the vein. The drug may be injected through an injection site on IV tubing or an intermittent infusion device. Most IV push medications should be injected slowly. The time depends on the particular drug, but is often 2 minutes or longer for a dose. Rapid injection should generally be avoided because the drug produces high blood levels and is quickly circulated to the heart and brain, where it may cause adverse or toxic effects. Although IV push may be useful with a few drugs or in emergency situations, slower infusion of more dilute drugs is usually preferred. Intermittent infusion is administration of intermittent doses, often diluted in 50 to 100 mL of fluid and infused over 30– 60 minutes. The drug dose is usually prepared in a pharmacy and connected to an IV administration set that controls the amount and flow rate. Intermittent infusions are often connected to an injection port on a primary IV line, through which IV fluids are infusing continuously. The purpose of the primary IV line may be to provide fluids to the client or to keep the vein open for periodic administration of medications. The IV fluids are usually stopped for the medication infusion, then restarted. Drug doses may also be infused through an intermittent infusion device (eg, a heparin lock) to conserve veins and allow freedom of motion between drug doses. The devices decrease the amount of IV fluids given to patients who do not need them (ie, who are able to ingest adequate amounts of oral fluids) and those who are at risk of fluid overload, especially children and older adults. An intermittent infusion device may be part of an initial IV line or used to adapt a continuous IV for intermittent use. The devices include a heparin lock or a resealable adapter added to a peripheral or central IV catheter. These devices must be flushed routinely to maintain patency. If the IV catheter has more than one lumen, all must be flushed, whether being used or not. Saline is probably the most commonly used flushing solution; heparin may also be used if recommended by the device’s manufacturer or required by institutional policy. For example, heparin (3 to 5 mL of 100 units/mL, after each use or monthly if not in use) is recommended for implanted catheters. Continuous infusion indicates medications mixed in a large volume of IV fluid and infused continuously, over several hours. For example, vitamins and minerals (eg, potassium chloride) are usually added to liters of IV fluids. Greater dilution of the drug and administration over a longer time decreases risks of accumulation and toxicity, as well as venous irritation and thrombophlebitis. Equipment Equipment varies considerably from one health care agency to another. Nurses must become familiar with the equipment available in their work setting, including IV catheters, types of IV tubing, needles and needleless systems, types of volume control devices, and electronic infusion devices (IV pumps). Catheters vary in size (both gauge and length), design and composition (eg, polyvinyl chloride, polyurethane, silicone). The most common design type is over the needle; the needle is used to start the IV, then it is removed. When choosing a catheter to start an IV, one that is much smaller than the



BOX 3–2


• When possible, avoid the antecubital vein on the inner surface
of the elbow, veins over or close to joints, and veins on the inner aspect of the wrists. Reasons include the difficulty of stabilizing and maintaining an IV line at these sites. In addition, the antecubital vein is often used to draw blood samples for laboratory analysis and inner wrist venipunctures are very painful. Do not perform venipuncture in foot or leg veins. The risks of serious or fatal complications are too high. Rotate sites when long-term use (more than a few days) of IV fluid or drug therapy is required. Venous irritation occurs with longer duration of site use and with the administration of irritating drugs or fluids. When it is necessary to change an IV site, use the opposite arm if possible.

• For any IV medication that is prepared or added to an IV bag,
label the medication vial or IV bag with the name of the patient, drug, dosage, date, time of mixing, expiration date, and the preparer’s signature. Drug Administration • Most IV medications are injected into a self-sealing site in any of several IV set-ups, including a scalp–vein needle and tubing, a plastic catheter connected to a heparin lock or other intermittent infusion device, or IV tubing and a plastic bag containing IV fluid. • Before injecting any IV medication, be sure the IV line is open and functioning properly (eg, catheter not clotted, IV fluid not leaking into surrounding tissues, phlebitis not present). If leakage occurs, some drugs are very irritating to subcutaneous tissues and may cause tissue necrosis. • Maintain sterility of all IV fluids, tubings, injection sites, drug solutions, and equipment coming into contact with the IV system. Because medications and fluids are injected directly into the bloodstream, breaks in sterile technique can lead to serious systemic infections (septicemia) and death. • When two or more medications are to be given one after the other, flush the IV tubing and catheter (with the infusing IV fluid or with sterile 0.9% sodium chloride injection) so that the drugs do not come into contact with each other. • If a medication is to be injected or infused through an intermittent infusion device containing heparin, the drug should be compatible with heparin or the device should be irrigated with sterile saline before and after medication administration. After irrigation, heparin then needs to be reinstilled. This is not a common event, because most heparin locks and other intermittent infusion devices are now filled with saline rather than heparin. • In general, administer slowly to allow greater dilution of the drug in the bloodstream. Most drugs given by IV push (direct injection) can be given over 2–5 minutes and most drugs diluted in 50–100 mL of IV fluid can be infused in 30–60 minutes. • When injecting or infusing medications into IV solutions that contain other additives (eg, vitamins, insulin, minerals such as potassium or magnesium), be sure the medications are compatible with the other substances. Consult compatibility charts (usually available on nursing units) or pharmacists when indicated. • IV flow rates are usually calculated in mL/hour and drops per minute. Required information includes the amount of solution or medication to be infused, the time or duration of the infusion, and the drop factor of the IV administration set to be used. The drop factor of macrodrip sets may be 10, 15, or 20 drops per milliliter, depending on the manufacturer. Most agencies use mainly one manufacturer’s product. The drop factor of all microdrip sets is 60 drops per mL. Following is a sample calculation: Order: Cefazolin 1 g IV q8h Label: Cefazolin 1 g in 100 mL of 0.9% sodium chloride injection; infuse over 60 minutes Solution: Divide 100 by 60 to determine mL/min (1.66). Multiply 1.66 by the drop factor to determine drops/min (eg, with a drop factor of 20 drops/mL, 33 drops/min would deliver the dose). Count drops and regulate the flow rate manually or program an IV pump to deliver the dose.

Drug Preparation Most IV drugs are prepared for administration in pharmacies and this is the safest practice. When a nurse must prepare a medication, considerations include the following. • Only drug formulations manufactured for IV use should be given IV. Other formulations contain various substances that are not sterile, pure enough, or soluble enough to be injected into the bloodstream. In recent years, there have been numerous reports of medication errors resulting from IV administration of drug preparations intended for oral use!! Such errors can and should be prevented. For example, when liquid medications intended for oral use are measured or dispensed in a syringe (as they often are for children, adults with difficulty in swallowing tablets and capsules, or for administration through a gastrointestinal [GI] tube), the syringe should have a blunt tip that will not connect to or penetrate IV tubing injection sites. • Use sterile technique during all phases of IV drug preparation. • Follow the manufacturer’s instructions for mixing and diluting IV medications. Some liquid IV medications need to be diluted prior to IV administration and powdered medications must be reconstituted appropriately (eg, the correct amount of the recommended diluent added). The diluent recommended by the drug’s manufacturer should be used because different drugs require different diluents. In addition, be sure any reconstituted drug is completely dissolved to avoid particles that may be injected into the systemic circulation and lead to thrombus formation or embolism. A filtered aspiration needle should be used when withdrawing medication from a vial or ampule, to remove any particles in the solution. The filter needle should then be discarded, to prevent filtered particles from being injected when the medication is added to the IV fluid. Filters added to IV tubing also help to remove particles. • Check the expiration date on all IV medications. Many drugs have a limited period of stability after they are reconstituted or diluted for IV administration. • IV medications should be compatible with the infusing IV fluids. Most are compatible with 5% dextrose in water or saline solutions. • If adding a medication to a container of IV fluid, invert the container to be sure the additive is well mixed with the solution.



Nursing Notes: Apply Your Knowledge
Your client has a nasogastric feeding tube in place. You will be administering morning medications, including 4 tablets, 1 capsule, and 10 cc of an elixir. Describe how you will safely administer medications through a feeding tube to this client.

cannot be reused. When vials or ampules contain a powder form of the drug, a sterile solution of water or 0.9% sodium chloride must be added and the drug dissolved before withdrawal. Use a filter needle to withdraw the medication from an ampule or vial because broken glass or rubber fragments may need to be removed from the drug solution. Replace the filter needle with a regular needle before injecting the client. Many injectable drugs (eg, morphine, heparin), are available in prefilled syringes with attached needles. These units are inserted into specially designed holders and used like other needle/syringe units.

In many settings, needleless systems are being used. These involve a plastic tip on the syringe that can be used to enter vials and injection sites on IV tubing. Openings created by the tip reseal themselves. Needleless systems were developed because of the risk of injury and spread of blood-borne pathogens, such as the viruses that cause acquired immunodeficiency syndrome and hepatitis B. Syringes also are available in various sizes. The 3-mL size is probably used most often. It is usually plastic and is available with or without an attached needle. Syringes are calibrated so that drug doses can be measured accurately. However, the calibrations vary according to the size and type of syringe. Insulin and tuberculin syringes are used for specific purposes. Insulin syringes are calibrated to measure up to 100 units of insulin. Safe practice requires that only insulin syringes be used to measure insulin and that they be used for no other drugs. Tuberculin syringes have a capacity of 1 mL. They should be used for small doses of any drug because measurements are more accurate than with larger syringes.

Equipment for Injections
Sterile needles and syringes are used to measure and administer parenteral medications; they may be packaged together or separately. Needles are available in various gauges and lengths. The term gauge refers to lumen size, with larger numbers indicating smaller lumen sizes. For example, a 25-gauge needle is smaller than an 18-gauge needle. Choice of needle gauge and length depends on the route of administration, the viscosity (thickness) of the solution to be given, and the size of the client. Usually, a 25-gauge, 5⁄8-inch needle is used for SC injections and a 22- or 20-gauge, 11⁄2-inch needle for IM injections. Other needle sizes are available for special uses, such as insulin or intradermal injections. When needles are used, avoid recapping them and dispose of them in appropriate containers. Such containers are designed to prevent accidental needle-stick injuries to health care and housekeeping personnel.

Sites for Injections
Common sites for subcutaneous injections are the upper arms, abdomen, back, and thighs (Fig. 3–1). Sites for intramuscular injections are the deltoid, dorsogluteal, ventrogluteal, and vastus lateralis muscles. These sites must be selected by first identifying anatomic landmarks (Fig. 3–2). Common sites for intravenous injections are the veins on the back of the hands and on the forearms (Fig. 3–3). Other sites (eg, subclavian and jugular veins) are also used, mainly in critically ill clients. Additional parenteral routes include injection into layers of the skin (intradermal), arteries (intra-arterial), joints (intraarticular), and cerebrospinal fluid (intrathecal). Nurses may administer drugs intradermally or intra-arterially (if an established arterial line is present); physicians administer intraarticular and intrathecal medications.

Figure 3–1

Subcutaneous injection sites.




Gluteus medius Gluteus maximus

Posterior superior iliac spine


Mid-deltoid area

Brachial vessels

Sciatic nerves Superior gluteal artery

Ventrogluteal area Anterior superior (in triangle) iliac spine

Greater trochanter of the femur


Greater trochanter of femur

Greater trochanter

Mid-portion vastus lateralis


Iliac crest X

Posterior edge iliac crest


Figure 3–2 IM injection sites. (A) Placement of the needle for insertion into the deltoid muscle. The area of injection is bounded by the lower edge of the acromion on the top to a point on the side of the arm opposite the axilla on the bottom. The side boundaries of the rectangular site are parallel to the arm and one third and two thirds of the way around the side of the arm. (B) Proper placement of the needle for an intramuscular injection into the dorsogluteal site. It is above and outside a diagonal line drawn from the greater trochanter of the femur to the posterior superior iliac spine. Notice how this site allows the nurse to avoid entering an area near the sciatic nerve and the superior gluteal artery. (C) Placement of the needle for insertion into the ventrogluteal area. Notice how the nurse’s palm is placed on the greater trochanter and the index finger on the anterior superior iliac spine. The middle finger is spread posteriorly as far as possible along the iliac crest. The injection is made in the middle of the triangle formed by the nurse’s fingers and the iliac crest. (D) Placement of the needle for insertion into the vastus lateralis. It is usually easier to have the client lying on his or her back. However, the client may be sitting when using this site for intramuscular injections. It is a suitable site for children when the nurse grasps the muscle in her hand to concentrate the muscle mass for injection.

Read the medication administration record (MAR) carefully. to prevent contamination or spilling of medications. Also. calculating dosages. and cleansing injection sites with an antiseptic. e. using sterile drug solutions. dosage or concentration. b. Wash hands before preparing medications and. Read the label on the drug container. Do not leave medications unattended. if needed. For accurate drug administration. and before returning the container. as free of interruptions and distractions as possible. Follow general rules for administering medications safety and effectively. and identifying clients To prevent infection and cross-contamination To prevent infection. . not touching sterile objects to any unsterile objects. c. Use sterile technique in preparing and administering injections.CHAPTER 3 ADMINISTERING MEDICATIONS 41 Cephalic vein Basilic vein Brachial artery Accessory cephalic vein Cephalic vein Radial artery Median cubital vein Ulnar artery Median antebrachial vein Basilic vein Cephalic vein Basilic vein Dorsal venous arch Superficial veins of the forearm Digital veins Metacarpal veins Superficial veins of the dorsal aspect of the hand Figure 3–3 Veins of the hand and forearm that may be used to administer intravenous fluids and medications. NURSING ACTIONS NURSING ACTIONS Drug Administration RATIONALE/EXPLANATION 1. Sterile technique involves using sterile needles and syringes. and route of administration. during administration. and compare with the MAR in terms of drug. a. To prevent accidental or deliberate ingestion by anyone other than the intended person. (continued ) d. Prepare and give drugs in well-lighted areas. Most nursing texts instruct the nurse to read a drug label three times: when removing the container. while measuring the dose. To prevent errors in selecting ordered drugs.

However. Common exceptions are antacids. Position the client appropriately for the intended route of administration. Administration of PRN medications requires nursing assessment and decision making. nitroglycerin. (3) Give before. the decision to give the dose later or omit it depends largely on the drug and frequency of administration. and frequency of administration. hold the cup at eye level. call the physician for clarification before giving the drug. If it is necessary to omit a scheduled dose for some reason. For suspensions. and give the cup to the client. Do not leave medications at the bedside as a general rule. relying on the name on a door or bed. or after meals as indicated by the specific drug. preferably by comparing the identification wristband to the medication sheet. For medications ordered as needed (PRN). Generally. For narcotics and other controlled substances. To promote dissolution and absorption of tablets and capsules. p. Analgesics. diluent may be given rather than the active drug. and if not mixed. A temporary change in the time of administration—usually for one dose only— may be necessary to maintain therapeutic effects. To maintain clean technique and measure doses accurately. drugs are not omitted without a careful assessment of the client’s condition and a valid reason. . and antipyretics are often ordered PRN. Do not give a drug when signs and symptoms of toxicity are present. Giving drugs at appropriate times in relation to food intake can increase therapeutic effects and decrease adverse effects. For example. at any time during drug preparation or administration. if indicated. “I’m . Calling by name. m. Also. Provide water or other supplies as needed. Notify the physician. the dose. Record drug administration (or omission) as soon as possible and according to agency policies. For others. check the physician’s orders or MAR for the name. The same procedure applies when the client questions drug orders at the bedside. It also decreases gastric irritation. With adults (1) To give tablets or capsules. shake or invert containers to mix the medication before measuring the dose. g. k. open the unit-dose wrapper. Identify yourself. I have your medication for you. and give the drug at the next scheduled time. such as aspiration of oral drugs into the lungs To promote comfort of the client and to ensure drug administration To prevent omitting or losing the drug or hoarding of the drug by the client Additional doses of a drug increase toxicity. dose. Identify the client. and eye medications. give drugs ordered once or twice daily at a later time.” h. and record that the drug was omitted and why. To decrease risks of aspirating medication into lungs. To maintain an accurate record of drugs received by the client Clients may be unable to take the drug at the scheduled time because of diagnostic tests or many other reasons. place medication in a medicine cup. Aspiration may lead to difficulty in breathing and aspiration pneumonia. the client may state he has been receiving different drugs or different doses. . any question arises regarding the drug. and measure the dosage at the bottom of the meniscus. Food in the stomach usually delays drug absorption and action. For oral medications: a. To prevent complications. j. antiemetics. with. . (2) Have the client in a sitting position when not contraindicated. If. Suspensions settle on standing. l. omit the one dose. If the order is not clear. to decrease gastric irritation by diluting drug concentration. RATIONALE/EXPLANATION This is the best way to verify identity. or whether the client is supposed to receive it.42 SECTION 1 INTRODUCTION TO DRUG THERAPY NURSING ACTIONS f. Explaining actions helps to decrease client anxiety and increase cooperation in taking prescribed medication. For example. and determine the time of the most recently administered dose. and state your reason for approaching the client. sign drugs out on separate narcotic records according to agency policies. 2. To meet legal requirements for dispensing controlled substances To promote safety and prevent errors. For solutions. although they must be used occasionally when the client lacks a name band. assess the client’s condition. i. and asking someone else are unreliable methods. check the original physician’s order. a common side effect of oral drugs. (continued ) (4) Give most oral drugs with a full glass (8 oz) of water or other fluid. o. n.

no benefit results from the drug. d. fluid and electrolyte problems may result from loss of gastric acid. Also. 5⁄8-inch needle for most SC injections. Do not give oral drugs if the client is: (1) NPO (receiving nothing by mouth) RATIONALE/EXPLANATION Children under 5 years of age are often unable to swallow tablets or capsules. crush a tablet or empty a capsule into about 30 mL of water and mix well. For subcutaneous (SC) injections: a. Use a clean bulb syringe or other catheter-tipped syringe. New orders are written postoperatively. and follow it with at least 50 mL of water. Oral drugs and fluids may interfere with diagnostic tests or be otherwise contraindicated. preoperative drug orders are cancelled. The syringe allows aspiration and serves as a funnel for instillation of medication and fluids into the stomach. To be sure the tube is in the stomach Gravity flow is safer than applying pressure. which occur with repeated injections in the same location. To avoid removing the medication from the stomach (2) Vomiting (3) Excessively sedated or unconscious 3. b. such as with insulin. If the client is very thin. (2) Medications are often mixed with juice. Clamp off the tube from suction or drainage for at least 30 minutes. With children. In long-term therapy. If this is done. applesauce. with possible client discomfort. d. This size needle is effective for most clients and drugs. tightening the skin may be easier. For medications given by nasogastric tube: a. rotate injection sites. Giving slowly decreases risks of aspiration. Select an appropriate injection site. bruises.CHAPTER 3 ADMINISTERING MEDICATIONS 43 NURSING ACTIONS b. If necessary. To avoid aspiration of drugs into the lungs owing to impaired ability to swallow Particles of tablets or powders from capsules may obstruct the tube lumen. For accurate measurement and administration. liquids or chewable tablets are usually given. Water “pushes” the drug into the stomach and rinses the tube. e. c. placing medication on the tongue or buccal mucosa and giving slowly. and do not empty sustained-release capsules. Tighten the skin or pinch a fold of skin and tissue between thumb and fingers. otherwise. To increase the child’s ability and willingness to take the medication. If the client is having surgery. Cleanse the site with an alcohol sponge. Use enough force to penetrate the skin and subcutaneous tissue in one smooth movement. the tissue fold may keep the needle from hitting bone. Do not allow the syringe to empty completely between additions. and insert the needle quickly at a 45-degree angle. or other vehicle. thereby maintaining tube patency. aspirate gastric fluid or use another method to check tube placement. and increase client comfort and cooperation To prevent infection Either is acceptable for most clients. Altering sustained-release products increases risks of overdosage and adverse effects. 4. Oral drugs and fluids increase vomiting. use a small amount. Hold the syringe like a pencil. avoid tissue damage and unpredictable absorption. (continued ) . e. and visual inspection of possible sites. based on client preferences. c. f. c. b. Use a liquid preparation when possible. Use only sterile drug preparations labeled or commonly used for SC injections. (1) Measure and give liquids to infants with a dropper or syringe. To give the drug correctly with minimal client discomfort. Additional water or other fluids may be given according to fluid needs of the client. drug characteristics. Thus. If the client is obese. Many parenteral drugs are too irritating to subcutaneous tissue for use by this route. Most drugs can be given after diagnostic tests are completed. Add fluids to avoid instilling air into the stomach unnecessarily. Use a 25-gauge. or other lesions. less than the ordered dose is given. Avoid areas with lumps. Do not crush enteric-coated or sustained-release products. Before instilling medication. Instill medication by gravity flow. and be sure the child takes all of it. These techniques allow the client to participate in his or her care.

select a site in the arm. povidone-iodine or alcohol). drugs are mixed and added to IV fluids in the pharmacy. and insert the needle quickly at a 90-degree angle. Release the skin so that both hands are free to manipulate the syringe. For venipuncture and direct injection into a vein.45). Remove the needle quickly and apply pressure for several seconds. bruises. Use the smallest-gauge needle that will accommodate the medication. Most drug solutions can be given with dextrose or dextrose and sodium chloride IV solutions. The length of time required to give the drug depends on the specific drug and the amount. Slow administration. Pull back gently on the plunger (aspirate). and aspirate a small amount of blood into the syringe to be sure that the needle is in the vein. and avoid areas with lumps. Prepare drugs just before use. To prevent infection To give the drug correctly with minimal client discomfort To prevent bleeding Others are not pure enough for safe injection into the bloodstream or are not compatible with the blood pH (7. In some agencies. hold the syringe like a pencil. For safe and accurate drug administration with minimal risk to the client. Aspirate (see 4g. Also. anatomic landmarks. as a general rule. allows immediate discontinuation if adverse effects occur. Identification of anatomic landmarks is mandatory for safe administration of IM drugs. inject the drug. If blood is aspirated into the syringe. h. A 22-gauge is satisfactory for most drugs. Most drugs in powder form can be dissolved in sterile water or sodium chloride for injection. Use enough force to penetrate the skin and subcutaneous tissue into the muscle in one smooth motion. For intravenous (IV) injections: a. Select an appropriate injection site. SC injections). add drugs to IV fluids just before use. Remove the needle quickly and apply gentle pressure for a few seconds. RATIONALE/EXPLANATION To prevent accidental injection into the bloodstream. based on client preferences. Some drugs are unstable in solution. c. Some drugs require special preparation techniques to maintain solubility or pharmacologic activity.35–7. 6. drug characteristics. Remove the tourniquet. and inject the drug slowly. If no blood enters the syringe. and visual inspection of possible sites. (continued ) . and reprepare the medication. which underlies subcutaneous fat. To prevent bleeding Some parenteral drug preparations cannot be given safely by the IM route. Remove the needle and apply pressure until there is no evidence of bleeding. Cleanse the site with an alcohol sponge. To decrease tissue damage and client discomfort To increase client comfort and participation and to avoid tissue damage. a 20-gauge may be used for viscous medications. b.44 SECTION 1 INTRODUCTION TO DRUG THERAPY NURSING ACTIONS g. d. 5. For intramuscular (IM) injections: a. Blood return in the syringe is an uncommon occurrence. h. cleanse the skin with an antiseptic (eg. A long needle is necessary to reach muscle tissue. e. g. or other lesions. Use only drug preparations that are labeled for IV use. f. d. depending on the size of the client. Rotate sites if frequent injections are being given. Use a 11⁄2-inch needle for most adults and a 5⁄8. Tighten the skin. b. c. Check label instructions for mixing drugs in powder form.to 11⁄2-inch needle for children. insert the needle. This is the preferred method because sterility can be better maintained. Check label instructions for the type and amount of fluid to use for dissolving or diluting the drug. over several minutes. Use only drug preparations labeled or commonly used for IM injections. remove the needle. apply a tourniquet.

When nose drops are used for rhinitis and nasal congestion accompanying the common cold. For application to skin: a. Most tubings have injection sites to facilitate drug administration. Provide a tissue for blotting any excess drug. depending on the drug. do not give the drug until a new IV line is begun. fill it with 50–100 mL of IV fluid. remove any previously applied medication. wait 1–5 minutes between instillations. cleanse an injection site on the IV tubing. Open the ear canal by pulling the ear up and back for adults. Do not mix drugs in syringes or in IV fluids unless the drug literature states that the drugs are compatible. Wash your hands. This method is used for administration of antibiotics on an intermittent schedule. not on the eyeball. add solution to maintain the infusion. insert the needle. (3) To use a volume-control set. Inject the drug into an injection site after cleansing the site with an alcohol sponge and infuse. Infuse the drug over 15–60 minutes. gently retract the lower lid. prepare the medication. Physical and chemical interactions between the drugs may occur and cause precipitation. If infiltration or phlebitis is present. 9. or information may be obtained from the pharmacy. f. Cleanse the skin. To promote therapeutic effects and minimize adverse effects Ophthalmic preparations must be sterile to avoid infection. (2) For direct injection. Use drug preparations labeled for ophthalmic use. and drop the medication on the side of the canal. This method is also used for intermittent administration of antibiotics and other drugs. For instillation of nose drops and nasal sprays: a. and instill the medication into the conjunctival sac. 7. instill the medication. flush the line between drugs. Check the venipuncture site for signs of infiltration and phlebitis before each drug dose. (4) To use a “piggyback” method. and apply the drug in a thin layer. place the child in a prone position. and clamp it so that no further fluid enters the chamber and dilutes the drug. For instillation of eye drops: a. and drop the medication into the nostrils. 8. 10. or increased toxicity. steady the hand holding the medication on the child’s head. or cotton-tipped applicator to apply the drug. To straighten the canal and promote maximal contact between medication and tissue (continued ) . For instillation of ear medications: a. Dilution of the drug decreases adverse effects. down and back for children. Have the client hold his or her head back. and maintain the position for 2–3 minutes. usually in 1 hour or less. Blot any excess drug from the inner canthus near the nose to decrease systemic absorption of the drug. and inject the drug slowly. RATIONALE/EXPLANATION The solution must be flowing freely for accurate drug administration. Then. overuse results in a rebound congestion that may be worse than the original symptom. tongue blade. Insert the needle in an injection site on the main IV tubing after cleansing the site. Once the drug is infused. Whether a volume-control or piggyback apparatus is used depends on agency policy and equipment available. When more than one drug is to be given. inactivation. open the eye to expose the conjunctival sac. and drop the medication into the sac. place the child in a head-lowered position. For administration by an established IV line: (1) Check the infusion for patency and flow rate.CHAPTER 3 ADMINISTERING MEDICATIONS 45 NURSING ACTIONS e. Use drug preparations labeled for dermatologic use. without touching the dropper tip to anything. For broken skin or open lesions. add the drug to 50–100 mL of IV solution in a separate container. use sterile gloves. Attach the IV tubing and a needle. Give only as ordered With children. If two or more eye drops are scheduled at the same time. Careful positioning and restraint to avoid sudden movements are necessary to decrease risks of injury to the eye. place in a supine position with the head lowered. With children. Most nursing units have charts depicting drug compatibility.

Metered dose inhalers. Use gloves or an applicator for insertion.. language and culture may have been a factor. D. 26–32. Small feeding tubes occlude very easily and must be rinsed well to prevent clogging. P. RATIONALE/EXPLANATION To promote absorption. R. (2000). Lubricate the end with a water-soluble lubricant. If an applicator is used. Be sure the client knows the correct procedure. then flush the tube again. Also. N. To administer. which dosage forms are acceptable? Which are unacceptable. For rectal suppositories: a. Which dosage forms must be kept sterile during administration? 5. St. Plumer’s Principles and practice of intravenous therapy. Craven. The ten most common lethal medication errors in hospital patients. W. For a client who receives all medications through a nasogastric feeding tube. 12. 3rd ed. L. When giving an oral medication. Drug facts and comparisons. What are some legal factors that influence a nurse’s administration of medications? 6. (2001). Note: Do not crush enteric-coated or sustainedrelease products because this alters their rate of absorption and could be dangerous to the client. 7th ed. What safety precautions must the nurse practice consistently to avoid self-injury and exposure to blood-borne pathogens? 8. the client had been asleep and may have been responding simply to being awakened. 35(5). F. Use liquid preparations when possible. J. If the client prefers and is able. give each medication separately and rinse the tube between medications. flush the feeding tube with tap water. A. Philadelphia: Lippincott Williams & Wilkins.46 SECTION 1 INTRODUCTION TO DRUG THERAPY NURSING ACTIONS 11. provide supplies for selfadministration. and insert into the rectum the length of the finger. especially when the client may be confused or unable to respond appropriately. When all medications are given. draw medication into a syringe. K. crush a tablet or empty a capsule into 15 to 30 mL of warm water and mix well. The nurse did not check the client’s name band and relied on the client to respond to her calling his name. When administering medications. C. S. Accurate identification of the client is imperative. Hospital Pharmacy. what approaches or interventions might persuade the client to take the medication? Would the same approach be indicated if the medication were a vitamin supplement or a laxative? Nursing Notes: Apply Your Knowledge Answer: First check tube placement by aspirating gastric content or instilling air into the stomach (listen with a stethoscope for a swishing sound over the gastric area). Preferably. Weinstein. In this situation. K. 2. S. SELECTED REFERENCES Argo. American Journal of Nursing. M. Fundamentals of nursing: Human health and function. what are some interventions to aid absorption and hasten therapeutic effects? . what safety precautions are needed with various routes? 7. Review and Application Exercises 1. & Brenner. Louis: Facts and Comparisons. Cox. For vaginal medications: a. If the client prefers and is able. Some women may be embarrassed and prefer self-administration. A.. flush the tube with 50 mL of water unless the client is on a fluid restriction. provide supplies for selfadministration. & Kelley. (2001). With a client who refuses an important medication. When a liquid formulation is not available. (Updated monthly). Place the suppository next to the mucosal wall. Togger. 470–474. & Hirnle. wash thoroughly with soap and water after each use. wear a glove or finger cot. How Can You Avoid This Medication Error? Answer: This medication error occurred because the medication was given to the wrong client. (2000). and why? 4. Allowing self-administration may prevent embarrassment to the client. and slowly instill the medication into the tube. 101(10). Be sure the client knows the correct procedure. Philadelphia: Lippincott Williams & Wilkins. What are the advantages and disadvantages of the oral route and the IV route of drug administration? 3.

chapter 4 Nursing Process in Drug Therapy Objectives AFTER STUDYING THIS CHAPTER. It may save lives. health–illness status. Identify nondrug interventions to prevent or decrease the need for drug therapy. Discuss application of the nursing process in home care settings. Chapter 3 emphasized drug preparation and administration. To fulfill this responsibility. 10. 3. and otherwise benefit recipients. teach clients about the potential effects of herbal and dietary supplements. this is only one aspect of the nursing process 47 . and social drugs as well as herbal and dietary supplements. and pathophysiology (alterations in mental and physical functions due to disease processes). Critical Thinking Scenario You are making the first home visit for an elderly client with arthritis and hypertension who is taking the following medications: Ibuprofen 800 mg every 4 hours Prednisone 5 mg daily Lasix 20 mg twice a day Captopril 25 mg twice a day Pepcid 20 mg at bedtime Look up each of these medications. Assess clients’ conditions in relation to age. 7. drug therapy is one of many responsibilities in client care. Observe clients for therapeutic and adverse responses to drug therapy. 5. 8. Describe major considerations in drug therapy for clients with impaired renal or hepatic function or critical illness. Obtain a medication history about the client’s use of prescription. and times of administration. Teach clients and family members how to use prescription and OTC drugs safely and effectively. the nurse must be D knowledgeable about pharmacology (drugs and their effects on the body). dosages. Discuss guidelines for rational choices of drugs. For the nurse. clients. weight. over-the-counter (OTC). physiology (normal body functions). Are these acceptable doses for elderly clients? What criteria will you use to determine therapeutic effects for each drug? Note any side effects that are likely for each drug and what assessment data will be important to collect. Physicians. OVERVIEW rug therapy involves the use of drugs to prevent or treat disease processes and manifestations. Although the importance of safe and accurate administration cannot be overemphasized. It also may cause adverse effects. 11. THE STUDENT WILL BE ABLE TO: 1. 4. 6. When indicated. Chapter 1 included general information about drugs and suggested strategies for studying pharmacology. pharmacists. and lifestyle habits likely to influence drug effects. improve the quality of life. routes. and must be adept at using all steps of the nursing process. Adverse effects and failure to achieve therapeutic effects may occur with correct use. For clients who use herbal and dietary supplements. 9. Chapter 2 described cellular physiology and concepts and processes essential to understanding drug effects in humans. Discuss interventions to increase benefits and decrease hazards of drug therapy. 2. and nurses all have important roles to play in the safe and effective use of drugs. provide or assist them in obtaining reliable information. Note the drug class and why you think this client is taking them. but they are more likely to occur with incorrect use.

and perceived benefits or adverse effects. family members. other nurses. It also may be helpful to ask about nonprescription drugs for headache. diabetes mellitus. client. laboratory reports. knowledge and informed. • Assess for previous and current use of prescription. and blood clotting tests before anticoagulant therapy. • If long-term drug therapy is likely. indigestion. because some people do not think of these preparations as drugs. It involves both cognitive and psychomotor skills. before drug therapy is started. Specific data to be acquired depend on the medication and the client’s condition. culture and susceptibility studies before antimicrobial therapy. how much and how often taken. and interventions. For example. and bone marrow function are often helpful because some drugs may damage these organs. Early recognition and treatment may prevent or decrease organ impairment. nursing diagnosis. • In addition to nursing assessment data. assess age. colds. pharmacists). Other data that may . this chapter includes nursing process guidelines. and other methods. To help the nurse continue to acquire knowledge and skills related to drug therapy. health status. echinacea. general principles of drug therapy. The nurse also must monitor responses to drug therapy. Also. is likely to comply with a prescribed drug regimen. caffeine. for how long. • Assess for previous or current use of herbal or dietary supplements (eg. The effects of these client-related factors on drug therapy are discussed in Chapter 2. ask for names. principles and actions related to specific drug groups and individual drugs are included in appropriate chapters throughout this text. Assessment Assessment involves collecting data about client characteristics known to affect drug therapy. rational thinking should underlie all data collection. both prescribed and OTC. Later assessments of a client’s condition and response to treatment are ongoing. or constipation. Although listed as the important first step in the nursing process. planning and establishing goals for nursing care. drug metabolism or excretion may be altered. and teach clients about drugs. all seriously ill clients should be assessed for risk factors and manifestations of impaired function of vital organs. medical records). such as those taken for chronic illnesses (eg. interviewing family members or others involved in client care. interventions. the initial assessment needs to be especially thorough because the information gained may guide the care provided by oneself. and other sources as available and relevant. both therapeutic and adverse. and general nursing actions. glucosamine/ chondroitin). the client may have therapy withheld inappropriately. Specific questions and areas of assessment include: • What are current drug orders? • What does the client know about current drugs? Is teaching needed? • What drugs has the client taken before? Include any drugs taken regularly. Some guidelines for obtaining needed assessment data are described below. • What are the client’s attitudes about drugs? Try to obtain information to help assess whether the client takes drugs freely or reluctantly. can the client afford to buy medications? Is transportation available for obtaining medications or seeing a health care provider for monitoring and follow-up care? • Can the client communicate his or her needs.48 SECTION 1 INTRODUCTION TO DRUG THERAPY in drug therapy. arthritis). Unless the reaction is further explored. completing a physical assessment. alcohol. and ability to function in usual activities of daily living. A medication history (Box 4–1) is useful. hypertension. what signs and symptoms occurred? This information is necessary because many people describe minor nausea and other symptoms as allergic reactions. they provide a basis for decisions about continuing or revising nursing care. decision-making. Some specific laboratory tests include serum potassium levels before diuretic therapy. cocaine. and nontherapeutic (eg. • On initial contact with a client. use progress notes. Knowledge and skill in the nursing process are required for drug therapy. The five steps of the nursing process are assessment. As part of the initial assessment. However. their reason for use. If so. One might say that assessment and interventions are the “action” phases whereas analysis of assessment data and establishing nursing diagnoses and goals are “thinking” phases. assessment is actually a component of all steps and occurs with every contact with the client. Laboratory tests of liver. or the information can be incorporated into any data collection tool. nonprescription. NURSING PROCESS IN DRUG THERAPY The nursing process is a systematic way of gathering and using information to plan and provide individualized client care and to evaluate the outcomes of care. and other health care providers (eg. reviewing medical records for pertinent laboratory and diagnostic test reports. • Has the client ever had an allergic reaction to a drug? If so. weight. such as requesting medication? Can he or she swallow oral medications? • Are any other conditions present that influence drug therapy? For example. if liver or kidney damage exists. marijuana) drugs. All available sources of assessment data should be used (eg. dietitians. as in other aspects of client care. gingko. This can be done by observing and interviewing the client. nicotine. and evaluation. Guidelines. pathologic conditions. kidney. or is likely to abuse drugs. obtain baseline data on measurements to be used in monitoring therapeutic or adverse effects.

Nursing Diagnoses These statements. as developed by the North American Nursing Diagnosis Association. acute and chronic Are you allergic to any medications? If yes.CHAPTER 4 NURSING PROCESS IN DRUG THERAPY 49 BOX 4–1 MEDICATION HISTORY Name___________________________________________________________________________ Age_________________________ Health problems. kava. Part 1: Prescription Medications 1. Name Dose Frequency Specific times How long taken Reason for use 3. gingko. Do you take any prescription medications on an irregular basis? If yes. ask for names. glucosamine/chondroitin. ask the following about each medication. any adverse effects. Do you have any difficulty in taking your medicines? If yes. Have you had any symptoms or problems that you think are caused by your medicines? If yes. describe client problems or needs and are based on assessment data. and other aspects of safe and effective drug therapy. nurses must provide care based on available information while knowing that assessment data are always relatively incomplete.)? If so. Amount/day Yes/No Name Amount Frequency be relevant include physical assessment data. Once assessment data are obtained. reason for use. Name Dose Frequency Reason How long taken Part 2: Nonprescription Medications Do you take over-the-counter medications? Medication Problem Pain Headache Sleep Cold Indigestion Heartburn Diarrhea Constipation Other Part 3: Social Drugs Yes/No Coffee Tea Cola drinks Alcohol Tobacco Part 4: Herbal or Dietary Supplements Do you take any herbal or dietary supplements (eg. • Seek information about ordered drugs. if needed. As a result. perceived effectiveness. With later contacts and after drug therapy is begun. 5. and urine output. ask to specify problem areas. assess the client’s response in relation to therapeutic and adverse effects. Do you need help from another person to take your medicines? 6. Thus. If yes. In general. ask to specify. Do you take any prescription medications on a regular basis? 2. 4. the nursing diagnoses needed to adequately . ask the following about each medication. they need to be analyzed for their relevance to the client’s current condition and nursing care needs. vital signs. how much and how often taken. ability and willing- ness to take the drugs as prescribed. describe specific effects or symptoms. weight. continued assessment is needed. They should be individualized according to the client’s condition and the drugs prescribed.

promoting compliance with the prescribed drug therapy regimen. however. General interventions include promoting health. rather than self-administered. For example. and others. These factors. ensuring that blood samples for serum drug levels are drawn at correct times in relation to drug administration helps to increase the usefulness and accuracy of these tests in monitoring the client’s condition. Some examples include: • Promoting healthful lifestyles in terms of nutrition. Other nursing interventions presented in a separate section of most chapters are the actions needed once a drug is ordered (ie. When medications are given by another caregiver. • Deficient Knowledge: Drug therapy regimen (eg.” General principles or guidelines are included in this chapter.50 SECTION 1 INTRODUCTION TO DRUG THERAPY reflect the client’s condition vary considerably. this text emphasizes those diagnoses that generally apply to any course of drug therapy. observing for drug interactions). the caregiver needs to understand about the medications. not nurse behavior. Some outcomes can be evaluated within a few minutes of drug administration (eg. assessing for therapeutic and adverse effects. require much longer periods of time. teaching about medications. rest. urine output. the client will: • Receive or take drugs as prescribed • Experience relief of signs and symptoms • Avoid preventable adverse drug effects • Avoid unnecessary drug ingestion • Self-administer drugs safely and accurately • Verbalize essential drug information • Keep appointments for monitoring and follow-up • Use any herbal and dietary supplements with caution • Report the use of herbal and dietary supplements to health care providers Interventions This step involves implementing planned activities and actually includes any task performed on a client’s behalf. For example. aminoglycoside antibiotics) helps to prevent ARF. Planning/Goals This step involves stating the expected outcomes of the prescribed drug therapy. These are presented under the heading of “Nursing Actions. Client Teaching Guidelines: Safe and effective use of prescription medications. Teaching aids to assist the nurse in this endeavor include Box 4–2: Preparing to teach a client or caregiver. and other assessment data Evaluation This step involves evaluating the client’s status in relation to stated goals and expected outcomes. and sleep • Handwashing and other measures to prevent infection • Positioning • Assisting to cough and deep breathe • Ambulating • Applying heat or cold • Increasing or decreasing sensory stimulation • Scheduling activities to allow periods of rest or sleep • Recording vital signs. With the current emphasis on outpatient treatment and short hospitalizations. financial assistance for obtaining medications). con- . goals should be stated in terms of client behavior. in clients at risk for developing acute renal failure (ARF). identifying resources (eg. Teaching about drug therapy is essential because most medications are selfadministered and clients need information and assistance to use therapeutic drugs safely and effectively. identifying barriers to compliance. and monitoring of response by health care providers. accurate administration. Because almost any nursing diagnosis may apply in specific circumstances. nursing interventions are integrated with background information and client characteristics to assist in individualizing care. Adequate knowledge and preparation are required to fulfill teaching responsibilities. solving problems related to drug therapy. drug ordered. As a general rule. ensuring adequate fluid intake and blood pressure and avoiding or following safety precautions with nephrotoxic drugs (eg. Later drug-related chapters contain client teaching guidelines for the drugs discussed in particular chapters. plus a client’s usual reluctance to admit noncompliance. and using nondrug measures to enhance therapeutic effects or to decrease adverse effects. and Client Teaching Guidelines: Safe and effective use of over-the-counter (OTC) medications. expected effects. Most. preventing or decreasing the need for drug therapy. including diagnostic tests and office visits) • Deficient Knowledge: Safe and effective selfadministration (when appropriate) • Risk for Injury related to adverse drug effects • Noncompliance: Overuse • Noncompliance: Underuse • Implementing specific interventions indicated by a particular drug or the client’s condition. fluid intake. These are presented under the heading of “Principles of Therapy. exercise. drug administration. and. those related to particular drug groups are included in later chapters. In addition. Client teaching as a nursing intervention is presented separately to emphasize its importance. the client is likely to experience brief contacts with many health care providers rather than extensive contacts with a few health care providers. reason for use. Areas of nursing intervention may include assessment. weighing seriously ill clients helps in calculating dosages of several drugs and in assessing changes in clients’ fluid balance or nutritional status. fluids.” and rationales for the interventions are included. relief of acute pain after administration of an analgesic). often extending from hospitalization and direct observation by the nurse to self-care at home and occasional contact with a health care provider.

The occurrence of severe reactions indicates that the drug should be stopped and the prescribing physician should be notified. Most drugs produce undesirable effects. provide specific instructions about taking the medications. the purpose can usually be simply stated in terms of symptoms to be relieved or other expected benefits. Usually. Clients and caregivers may feel overwhelmed by complicated medication regimens and are more likely to make errors with large numbers of medications or changes in the medication regimen. Many people stop taking a drug rather than report adverse reactions. Minimize medical jargon and be aware that clients may have difficulty understanding and retaining the material being taught because of the stress of the illness. nursing responsibilities related to drug therapy are designated in critical paths (also called clinical pathways or care maps). develop an individualized teaching plan. In addition. Treatment failure can often be directly traced to these errors. missed doses of glaucoma medication can lead to optic nerve damage and blindness. INTEGRATING NURSING PROCESS. Such knowledge is • • • • • • • • • • • tribute to difficulties in evaluating outcomes of drug therapy. discuss specific ways to take medications so that usual activities of daily living are minimally disrupted.CHAPTER 4 NURSING PROCESS IN DRUG THERAPY 51 BOX 4–2 PREPARING TO TEACH A CLIENT OR CAREGIVER a safety measure. CRITICAL PATHS AND DRUG THERAPY In many agencies. If side effects occur. if appropriate. it may be possible to continue drug therapy by reducing dosage. difficulty in breathing. These techniques may be used at every contact with a client. may help increase compliance with the prescribed regimen. Try to decrease their anxiety and provide positive reinforcement for effort. Choose an appropriate time (eg. forgetting to take doses. pharmacists) to learn about the drug and provide accurate information to the client. “pill counts” may be done to compare doses remaining with the number prescribed during a designated time. some are potentially serious. within the limitations imposed by individual drugs. such as relief of symptoms. teach them how to manage minor ones and which ones to report to a health care provider. If the drug is unfamiliar. For example. especially if an allergic or other potentially serious adverse reaction or overdose occurs. blood sugar with antidiabetic drugs. • Assess learning needs. and checking appropriate medical records. The client should also know the purpose of prescribed drugs. when medications are added because of a new illness or stopped). and why to take the medications. and stopping a medication too soon. From assessment data. With outpatients. Throughout the teaching session and perhaps at other contacts. selfadminister medications by ordered routes). Planning with a client to develop a convenient routine. If reactions are reported. and others. some are minor. When teaching a client about medications to be taken at home. Proceed slowly. Assess ability to manage a drug therapy regimen (ie. expected effects. of any drugs being taken. The client should know the name. taking doses at the wrong times. accurate adminis- tration. This includes finding out what the person already knows about a particular drug. Critical paths are guidelines for the care of . interviewing the client or others about the client’s response to drug therapy. Specific criteria indicate the parameters that must be measured to evaluate responses to particular drugs (eg. and so on. If the client has been taking a drug for a while. when the client is mentally alert and not in acute distress [eg. in small steps. emphasize the importance of taking medications as prescribed. • General criteria include progress toward stated outcomes. When explaining a drug therapy regimen to a hospitalized client. or other measures. remember dosage schedules. drug reference books. • Techniques include directly observing the client’s status. emphasize essential information. In many instances. compliance with instructions. from pain. use available resources (eg. the drug is familiar and can be described from personal knowledge. read printed instructions and drug labels. These difficulties can be managed by using appropriate techniques and criteria of evaluation. Allow time for questions and try to ensure that the client understands how. when. especially when new drugs are added or new conditions are being treated. or other symptoms]) and a place with minimal noise and distractions. This saves time for both nurse and client by avoiding repetition of known material. It also decreases the risk of mistaking one drug for another and promotes a greater sense of control and responsibility regarding drug therapy. the goal is to provide needed information without causing unnecessary anxiety. changing the time of administration. Common client errors include taking incorrect doses. Reassess learning needs when medication orders are changed (eg. a combination of verbal and written instructions is more effective than either alone. When teaching a client about potential adverse drug effects. purpose. blood pressure with antihypertensive drugs). and provide ample opportunities to express concerns or ask questions. preferably both the generic and a trade name. including medication records and laboratory and other diagnostic test reports. Do not assume that teaching is unneeded. avoidance of preventable adverse effects. Also teach the client and caregiver to observe for beneficial and adverse effects. verify by questions and observations that he or she already knows essential drug information and takes the drug correctly. Although people vary in the amount of drug information they want and need. It also promotes compliance with prescribed drug therapy. A medication history (see Box 4–1) helps to assess the client’s knowledge and attitudes about drug therapy. describe the name.

to prevent accidental ingestion. when possible. consult your obstetrician or pediatrician before taking any medications prescribed by another physician. ask a health care provider before splitting. One way to do this is to keep a written record of all current medicines. Altering the dose or time may cause underdosage or overdosage. other medications. ✔ Use nondrug measures. A schedule that minimally disrupts usual household activities is more convenient and more likely to be followed accurately. beverages. ✔ As a general rule. However. This is a safety factor to avoid undesirable drug interactions. . including their names and doses and how they are taken. Inform health care providers if you have diabetes or kidney or liver disease. responses may change over time with aging. chewing. Often. and for how long? Should it be taken with food or on an empty stomach? While taking this medicine. talk to a doctor. such as: What is the medicine’s name? What is it supposed to do (ie. report them to the prescribing physician rather than stopping the drug. in a sitting or standing position. Therapeutic effects greatly depend on taking medications correctly. take oral medications with 6–8 oz of water. Develop a plan for renewing or refilling prescriptions so that the medication supply does not run out when the prescribing physician is unavailable or the pharmacy is closed. If problems occur with taking the drug. The water helps tablets and capsules dissolve in the stomach. If breast-feeding. laboratory or other diagnostic tests that monitor therapeutic or adverse effects of drugs). It is a good idea to carry a copy of this list at all times. what symptoms or problems will it relieve)? How and when do I take it. changes in kidney function. ✔ ✔ ✔ ✔ ✔ ✔ Self-Administration ✔ Develop a routine for taking medications (eg. “dilutes” the drug so that it is less likely to upset the stomach. ✔ Take medications in a well-lighted area and read labels of containers to ensure taking the intended drug. If pregnant. ✔ Keep all health care providers informed about all the drugs being taken. and so on. an adjustment in dosage or other aspect of administration may solve the problem.52 SECTION 1 INTRODUCTION TO DRUG THERAPY CLIENT TEACHING GUIDELINES Safe and Effective Use of Prescription Medications General Considerations ✔ Use drugs cautiously and only when necessary because all drugs affect body functions and may cause adverse effects. This is an important safety factor in helping to avoid several prescriptions of the same or similar drugs and to minimize undesirable interactions of newly prescribed drugs with those already in use. This information can help avoid new prescriptions or OTC drugs that have similar effects or cancel each other’s effects. should I avoid certain foods. ✔ Follow instructions for follow-up care (eg. It may be helpful to remind the physician periodically of the medications being taken and ask if any can be discontinued or reduced in dosage. The likelihood of having the right drug in the right dose is remote and the risk of adverse effects is high in such circumstances. at the same time and place each day). office visits. including over-the-counter (OTC) products and herbal or dietary supplements. notify a health care provider if unable to obtain or take a medication.) Will this medication work safely with the others I’m already taking? What side effects are likely and what do I do if they occur? Will the medication affect my ability to sleep or work? What should I do if I miss a dose? Is there a drug information sheet I can have? Store medications out of reach of children and never refer to medications as “candy”. ✔ Do not take drugs left over from a previous illness or prescribed for someone else and do not share prescription drugs with anyone else. ✔ Get all prescriptions filled at the same pharmacy. pharmacist. Some medications need to be tapered in dosage and gradually discontinued. Some long-acting preparations are dangerous if altered so that the entire dose is absorbed at the same time. or nurse before starting an OTC medication or herbal or dietary supplement. The upright position helps the drug reach the stomach rather than getting stuck in the throat or esophagus. If unable to take them whole. With long-term use of a medication. ✔ Take drugs as prescribed and for the length of time prescribed. ✔ Ask questions (and write down the answers) about newly prescribed medications. These conditions require special precautions with drug therapy. to prevent the need for drug therapy or to enhance beneficial effects and decrease adverse effects of drugs. ✔ Report any drug allergies to all health care providers and wear a medical identification emblem that lists allergens. Some drugs require more frequent monitoring than others. ✔ Most tablets and capsules should be taken whole. Do not take medications if you are not alert or cannot see clearly. When taking prescription medications. alcoholic beverages and driving a car should be avoided with medications that cause drowsiness or decrease alertness. Stopping a medication may cause a recurrence of the problem for which it was given or withdrawal symptoms. safety requires periodic checks with essentially all medications. ✔ Take drugs in current use when seeing a physician for any health-related problem. and promotes absorption of the drug into the bloodstream. when possible. or crushing tablets or taking the medication out of capsules. consult your obstetrician before taking any medications prescribed by another physician. certain activities? (For example.

ask a health care provider whether they may be taken together or at different times. having many containers increases the risks of medication errors and adverse drug interactions. eye drops. ✔ If taking a liquid medication (or giving one to a child). case managers. aspects of care related to the medical diagnosis. if ordered once daily.CHAPTER 4 NURSING PROCESS IN DRUG THERAPY 53 CLIENT TEACHING GUIDELINES Safe and Effective Use of Prescription Medications (Continued ) ✔ Take most oral drugs at evenly spaced intervals around the clock. many clinical pathways have specific guidelines related to drug therapy. ✔ Follow instructions about taking a medication with food or on an empty stomach. especially if exposed to heat and moisture. and hip or knee replacement). For example. For example. The 1994 Dietary Supplement Health and Education Act (DSHEA) defined a dietary supplement as “a vitamin. phytochemicals. • Development and implementation of the critical paths should be an interdisciplinary. Depending on the medical diagnoses. In addition. If ordered twice daily or morning and evening. • In hospital settings. relieve. With assessment. an herb or other botanical used to supplement the diet. If a dose is omitted. heat. most authorities recommend taking the dose if remembered soon after the scheduled time and omitting the dose if it is not remembered for several hours. also called botanicals. other dietary supplements may be derived from a variety of sources. take about 12 hours apart. do not keep drugs for long periods. light. Although this may be more convenient. be sure to ask a health care provider. take about the same time every day. and moisture may cause them to decompose. This is especially important for young children because most of their medications are given in liquid form. measure with a calibrated medication cup or measuring spoon. • Medical diagnoses for which critical paths are developed are those often encountered in an agency and those that often result in complications or prolonged lengths of stay (eg.” Under this law. are derived from plants. all health care professionals usually involved in the care of a client with a particular medical diagnosis should be represented. A dose cannot be measured accurately with household teaspoons or tablespoons because they are different sizes and deliver varying amounts of medication. but the products cannot claim to diagnose. dry place. clients having coronary artery bypass grafts. If taking several medications. an antacid usually should not be taken at the same time as other oral medications because the antacid decreases absorption of many other drugs. a comprehensive pathway extending from illness onset through treatment and recovery could pro- mote continuity of care among agencies and health care providers. an additional nursing concern has emerged in the form of herbal and dietary supplements. herbs can be labeled according to their possible effects on the human body. Discard outdated medications. a mineral. Herbal medicines. usually assess clients’ conditions daily to evaluate progress toward the desired outcomes. prevent. myocardial infarction. Use other types of medications according to instructions. Do not store them in a bathroom. If the liquid medication is packaged with a measuring cup that shows teaspoons or tablespoons.” Herbal and Dietary Supplements In recent years. If not clear how a medication is to be used. Do not double the dose. Store medications safely. Keep medications in the container in which they were dispensed by the pharmacy. and neutraceuticals. Additional characteristics include the following: • Major components include a medical diagnosis. that should be used to measure doses. These guidelines may affect any step of the nursing process. Thus. for adults or children. about taking with other medications. which could be taken by mistake. and skin medications is essential for therapeutic effects. where the label identifies it and gives directions. who may be nonnurses. desired client outcomes. “Assess for bleeding if on anticoagulant. For clients. the critical path may state. ✔ If a dose is missed. for example. ✔ ✔ ✔ ✔ clients with particular conditions. and clients who take them are likely to be encountered in any clinical practice setting. it is never a safe practice because it increases the likelihood of taking the wrong drug. Drugs are chemicals that may deteriorate over time. Report problems or new symptoms to a health care provider. or cure . or taking with fluids other than water. Correct use of oral or nasal inhalers. collaborative effort. Do not store them near a dangerous substance. These supplements are increasingly being used. Prescription medications often include instructions to take on an empty stomach or with food. and time frames (usually days) for achieving the desired outcomes during the expected length of stay. especially when away from home for work or travel. Do not put several different tablets or capsules in one container. • Critical paths may be used in most health care settings. in a cool. the next dose should be taken at the next scheduled time.

Do not take a laxative if you have stomach pain. often in doses of 81 mg (a child’s dose) or 325 mg. are essentially unknown. For children. consult your obstetrician before taking any OTC medications. Coumadin). heart attack. in combination with other herbal and dietary supplements. Accurate measurement of doses is especially important for young children because most of their medications are given in liquid form. Claritin D). check expiration dates periodically and discard those that have expired. If such a device is not available. to avoid worsening the problem. What is the nursing role in relation to these products and safe and effective drug therapy? Two major concerns are that use of supplements may keep the client from seeking treatment from a health care provider when indicated and that the products may interact with prescription drugs to decrease therapeutic effects or increase adverse effects. Sudafed). It is not safe to use household teaspoons or tablespoons because they are different sizes and deliver varying amounts of medication. indications for use. selected herbal and dietary supplements with some scientific support for their use are described in more detail. ✔ Do not take OTC medications longer or in higher doses than recommended. In general. Measure liquid OTC medications with the measuring device that comes with the product (some have a dropper or plastic cup calibrated in milliliters. some products reported to be useful in relieving pain. Store OTC drugs in a cool. and other organs that occur with aging and various disease processes. friends. Because all these drugs cause drowsiness. when information is available and deemed clinically relevant. in Chapter 7. Some suggestions and guidelines include the following: • Seek information from authoritative. Sinutab). inflammation. use a measuring spoon. Older people are more likely to have adverse drug reactions and interactions because of changes in heart. Do not take a nasal decongestant (eg. Many OTC medications warn against use with certain illnesses (eg. Avoid OTC sleeping aids if you are taking a prescription sedative-type drug (eg. consult a health care provider before taking any nonprescription drugs to avoid undesirable drug interactions and adverse effects. Overall. or vomiting. in their original containers. teaspoons. a multisymptom cold remedy containing pseudoephedrine (eg. Most products have not been studied sufficiently to evaluate their safety or effectiveness. for nervousness or depression). For example. nausea. ask a physician. potentially dangerous. Ask a health care provider before taking products containing aspirin if you are taking an anticoagulant (eg. nurses need to have an adequate knowledge base and to incorporate their knowledge in all steps of the nursing process (see below). Some specific precautions include the following: Avoid alcohol if taking antihistamines. usual dosage. ✔ Note that all OTC medications are not safe for everyone. fever. possible side effects. • Client teaching guidelines. or stroke. to read the fine print.54 SECTION 1 INTRODUCTION TO DRUG THERAPY CLIENT TEACHING GUIDELINES Safe and Effective Use of Over-the-Counter (OTC) Medications ✔ Read product labels carefully. Actifed. The labels contain essential information about the name. Such products can raise blood pressure and decrease or cancel the blood pressure–lowering effect of the prescription drug. If breast-feeding. Ask a health care provider before taking other products containing aspirin if you are already taking a regular dose of aspirin to prevent blood clots. With the continued caution that relatively little reliable information is known about these products. consult your pediatrician or family doctor before taking any OTC medications. or tablespoons). Note tamper-resistant features and do not buy products with damaged packages. or personal testimonials from family members. thyroid disorders). kidneys. objective sources rather than product labels. Aspirin is commonly used for this purpose. ✔ Use a magnifying glass. Consult a health care provider before taking the product if you have one of the contraindicated conditions. or the herbal medicine ephedra (Ma Huang) if you are taking a prescription medication for high blood pressure. Do not assume continued safety of an OTC medication you have taken for years. This could lead to severe hypertension and stroke. general information is provided (see Client Teaching Guidelines: General information about herbal and dietary supplements). or nurse. and expiration dates. ✔ ✔ ✔ ✔ ✔ ✔ ✔ specific human diseases unless approved by the FDA. and in combination with pharmaceutical drugs. ✔ If you do not understand the information on labels. the effects of these products on particular consumers. several resources are provided in this text. ✔ If taking any prescription medications. If pregnant. ingredients. follow any age limits on the label. sedation. pharmacist. if necessary. or celebrities. or sleeping pills. combining any of them with alcohol may result in excessive. guidelines may emphasize avoidance or caution in using supplements (text continues on page 59) . In later chapters. when to stop using the medication or when to see a doctor. advertisements. an antihistamine-decongestant combination (eg. cough or cold remedies containing dextromethorphan. most available information involves self-reports of a few people. hypertension. including: • Table 4–1 describes some commonly used herbal and dietary supplements. In later chapters. or migraine. are described. dry place. In this chapter.

In overdose may cause nausea. asters. may cause occasional stomach upset. and headache • An amino acid produced in liver and kidneys and stored in muscles • Causes weight gain. and osteoarthritis. transport. with reports of shorter durations and possibly decreased severity of symptoms • Most often used for the common cold. twice daily • Not recommended for use longer than 6 months because long-term effects are unknown • Apparently has no effect on endometrium.CHAPTER 4 NURSING PROCESS IN DRUG THERAPY 55 TABLE 4–1 Name Black cohosh Herbal and Dietary Supplements Characteristics • Thought to relieve menopausal symptoms by suppressing the release of luteinizing hormone (LH) from the pituitary gland and dysmenorrhea by relaxing uterine muscle • Well tolerated. flushes. redness. a liquid. is derived) • Derived from the trachea cartilage of cattle slaughtered for food • Usually taken with glucosamine • Adverse effects minor. 7) Creatine Echinacea • Usually ingested as a tea • May cause contact dermatitis • May cause severe hypersensitivity reactions. and stinging Chamomile Chondroitin (see Chap. an oral anticoagulant. • Used to treat pain associated with neuralgia. • Self-defense as the active ingredient in “pepper spray” • Used mainly for antispasmodic effects in the gastrointestinal (GI) tract. purpurea most often used medicinally • Effects on immune system include stimulation of phagocytes and monocytes • Contraindicated in persons with immune system disorders because stimulation of the immune system may aggravate autoimmune disorders • Hepatotoxic with long-term use • Capsaicin is a topical analgesic that may inhibit the synthesis. nausea. in people allergic to ragweed. irritability) • May also relieve premenstrual syndrome (PMS) and dysmenorrhea Remarks • No apparent advantage over traditional estrogen replacement therapy (ERT) • May be useful when ERT is contraindicated for a client or the client refuses ERT • Recommended dose is 1 tab standardized to contain 20 mg of herbal drug. in small numbers of women. a peripheral neurotransmitter of pain. and chrysanthemums • May delay absorption of oral medications • May increase risks of bleeding (contains coumarins. neuropathy. itching. may relieve abdominal cramping Few studies and little data to support use and effectiveness in GI disorders Arthritis Several studies support use • Athletes take creatine supplements to gain extra energy. so progesterone not needed in women with an intact uterus Applied topically Capsaicin (see Chap. but also advertised for many other uses (immune system stimulant. may include GI upset. to train longer and harder. vomiting. visual disturbances. other trade names include Estroven and Femtrol Uses • Most often used to relieve symptoms of menopause (eg. and improve performance • Not recommended for use by children because studies have not been done and effects in children are unknown • Nurses and parents need to actively discourage children and adolescents from using creatine supplements • Hard to interpret validity of medicinal claims because various combinations of species and preparations used in reported studies • A few studies support use in common cold. as tablets and capsules • Many species but E. and reduced pulse rate • Most clinical trials done with Remefemin. 6) • Derived from cayenne pepper • Pain with first application • Adverse effects include skin irritation. including anaphylaxis. anti-infective) (continued ) . and release of substance P. usually within 2 weeks of starting use • Legal and available in health food stores as a powder to be mixed with water or juice. the substances from which warfarin. vaginal dryness. dizziness.

irritation of GI tract. chrysanthemums. bronchodilator. including death. seizures. cardiac dysrhythmias. heparin. A disadvantage is a delayed response. vomiting. cardiac palpitations) or who take medications associated with significant drug interactions (eg. dizziness. stimulant Remarks The Food and Drug Administration (FDA) has issued warnings against use of ephedra because of potentially severe adverse effects. including motion sickness and postoperative nausea Used mainly to improve memory and cognitive function in people with Alzheimer’s disease. and a recommendation to use no longer than 3 months. bleeding. • Although not recommended for use by anyone. asters. especially those of deodorized supplements Ginger Used mainly to treat nausea. 7) Migraines. clopidogrel) Uses Anorexiant for weight loss. vomiting • Inhibits platelet aggregation. although a recent study did not support its effectiveness for this purpose • Also used for antihypertensive and antibiotic effects. allergic skin reaction • May increase risks of bleeding with any drug that has antiplatelet effects (eg. decongestant. dermatitis). 18) • Commonly found in herbal weightloss products • May cause or aggravate hypertension. but there is little reliable evidence for such use Medicinal effects probably exaggerated. hypertension.56 SECTION 1 INTRODUCTION TO DRUG THERAPY TABLE 4–1 Name Ephedra (Ma Huang) Herbal and Dietary Supplements (continued ) Characteristics • Acts the same as the adrenergic drugs ephedrine and pseudoephedrine. headache. up to 6 or 8 weeks. should not be used with anticoagulants • May decrease blood sugar and cholesterol • Adverse effects include allergic reactions (asthma. nausea. nervousness. may increase clotting time • Gastroprotective effects in animal studies • Reportedly increases blood flow to the brain. Whether this shows clinically significant benefits is still unclear. improves memory and decreases dizziness and ringing in the ears (tinnitus) • Improves blood flow to legs and decreases intermittent claudication associated with peripheral arterial insufficiency • Antioxidant • Inhibits platelet aggregation • Adverse effects include GI upset. menstrual irregularities. headache. • In European studies. nausea. Feverfew (see Chap. arthritis Some studies support use in migraine Garlic • Used mainly to lower serum cholesterol levels. patients with intermittent claudication showed significant improvement. which are cardiac and central nervous system (CNS) stimulants as well as decongestants and bronchodilators (see Chap. tremor. ephedra is considered especially hazardous for people with conditions that might be aggravated (eg. decreased therapeutic effects or increased adverse effects). aspirin and other nonsteroidal anti-inflammatory drugs [NSAIDs]. myocardial infarctions • May increase effects of other cardiac and CNS stimulants and cause potentially life-threatening illnesses • May decrease effects of antihypertensive medications • May increase clotting time and risk of bleeding • May cause hypersensitivity reactions in people allergic to ragweed. Ginkgo biloba . or daisies • May cause withdrawal syndrome if use is stopped abruptly • Active ingredient is thought to be allicin • Has antiplatelet activity and may increase risk of bleeding. warfarin. strokes. seizures. may be useful in treating peripheral arterial disease Should not be used for morning sickness associated with pregnancy— may increase risk of miscarriage • Some studies indicate slight improvement in Alzheimer’s disease.

decreases blood glucose and cholesterol) • Adverse effects include hypertension. may depress or stimulate central nervous system [CNS]. or neutropenia • Should be avoided by people with hepatic disease. may include GI upset. lymphocytes. and edema. Caution clients to avoid ingesting excessive amounts. • A ginseng abuse syndrome. thrombocytopenia. • Instruct any client taking ginseng to avoid long-term use. weight loss. heparin. antidepression. inhibits platelet aggregation. diarrhea. gait. mania. depression. and vomiting • May increase risks of bleeding with any drug that has antiplatelet effects (eg. pupil dilation • Chronic heavy use may cause hematologic abnormalities (eg. pain. with symptoms of insomnia. bilirubin and urea). epistaxis. and promotion of wound healing • Use as a calming agent is supported by limited evidence from a few small clinical trials. urge him or her to check blood glucose frequently until ginseng’s effects on blood sugar are known. and hepatotoxicity • May increase effects of alcohol and other CNS depressants (any herb or drug that causes drowsiness and sedation). hypotonia. stress. more well-controlled studies are needed before the herb can be recommended for these uses. John’s wort. If a client insists on using. tranylcypromine). thus possible mood elevating. decreased platelets. Also to promote sleep and relieve depression Remarks • A few small studies in humans support benefits of ginseng in improving psychomotor and cognitive functioning and sleep. phenelzine. by enhancing effects of GABA (an inhibitory neurotransmitter in the CNS) • Adverse effects include impaired coordination. and tremors may occur • Usually used with chondroitin • Has beneficial effects on cartilage • Adverse effects mild. such combinations should be avoided Uses Used to increase stamina. additional claims include treatment of depression. rheumatism. headache. may have antiseizure effects • May act similarly to benzodiazepines. selegiline. • Diabetics should use ginseng very cautiously. aspirin and other NSAIDs. headache. strength. 8) Most studied and used to treat anxiety. and in children under 12 years old (continued ) . or hypertension to check with their primary physician before taking ginseng. has been reported. antistress. Several studies support use Glucosamine (see Chap. warfarin. St. because of its hypoglycemic effect alone and apparent ability to increase the hypoglycemic effects of insulin and oral antidiabetic drugs. pruritus. vaginal bleeding. amenorrhea. nausea. muscle spasms. if at all. and sedative effects. insomnia. asthma. and mental acuity. skin rashes. endurance. • Instruct clients with cardiovascular disease. emotional excitability and restlessness.CHAPTER 4 NURSING PROCESS IN DRUG THERAPY 57 TABLE 4–1 Name Ginseng Herbal and Dietary Supplements (continued ) Characteristics • Active ingredients called ginsenosides or panaxosides • Has a variety of pharmacologic effects that vary with dose and duration of use (eg. However. Siberian ginseng should not be used longer than 3 weeks. chest pain. drowsiness • Produces mild euphoria and sedation. impotence. headache. nervousness. other therapeutic claims are poorly documented • Should be used cautiously by people with renal disease. diabetes mellitus. 7) Arthritis Kava (see Chap. plasma proteins. during pregnancy and lactation. clopidogrel) • Increases risk of hypoglycemic reactions if taken concurrently with insulin or oral antidiabetic agents • Should not be taken concurrently with other herbs or drugs that inhibit monoamine oxidase (eg. palpitations. insomnia. and judgment.

may have antiandrogenic effects • Generally well tolerated. antivirals used to treat acquired immunodeficiency syndrome (AIDS).58 SECTION 1 INTRODUCTION TO DRUG THERAPY TABLE 4–1 Name Melatonin (Chap. but at least 10 potentially active components have been identified • Thought to act similarly to fluoxetine (Prozac). energy level. Also has muscle relaxant effects • Reportedly effective in doses of 320 mg/day for 1–3 months • Men should have a prostate specific antigen (PSA) test (a blood test for prostate cancer) before starting saw palmetto. and organ transplant drugs (eg. or neurologic disorders • Adverse effects include altered sleep patterns. mental alertness. hypersensitivity reactions. dizziness. cyclosponne) Saw palmetto Used mainly to relieve urinary symptoms in men with benign prostatic hyperplasia (BPH) Valerian (Chap. nausea. unsafe when combined with ephedra • Can decrease effectiveness of birth control pills. adverse effects usually minor but may include GI upset. risk of liver damage from combination products containing valerian and from overdoses averaging 2. insomnia.5 g • May cause additive sedation if combined with other CNS depressants. Diarrhea may occur with high doses Uses Used mainly for treatment of insomnia and prevention and treatment of jet lag Remarks Patients with renal impairment should use cautiously Saint John’s wort (Chap. 10) Used mainly for treatment of depression • Should not be combined with monoamine oxidase inhibitor (MAOI) or selective serotonin reuptake inhibitor (SSRI) antidepressants. headache. excitability. GI upset. 8) • Sedative effects may be due to increasing GABA in the brain • Adverse effects with acute overdose or chronic use include blurred vision. Also. a history of cerebrovascular disease. drowsiness. dizziness. headache. 8) Herbal and Dietary Supplements (continued ) Characteristics • Several studies of effects on sleep. itching. fatigue and confusion • May interact with numerous drugs to increase their effects. antineoplastic drugs. These include antidepressants. which increases serotonin in the brain • Studies (most lasting 6 months or less) indicate improvement in mild to moderate depression • Apparently not effective in major or serious depression • Adverse effects include photosensitivity (especially in fair-skinned persons). and mood indicate some improvement. these combinations should be avoided Used mainly to promote sleep and allay anxiety and nervousness. headache. sedation. • Should not be combined with sedative drugs and should not be used regularly • Many extract products contain 40–60% alcohol and may not be appropriate for all patients • Most studies flawed—experts do not believe there is sufficient evidence to support the use of valerian for treatment of insomnia . adrenergics and others • Action unknown. confusion. tachycardia • Active component thought to be hypericin. compared with placebo • Contraindicated in persons with hepatic insufficiency (especially cirrhosis. depression. because of slowed melatonin clearance). fatigue. because the herb can reduce levels of PSA and produce a false-negative result. probably by inhibiting their metabolism.

If so. and climate where the plants are grown. and surgical procedures. as are pharmaceutical drugs. water. “natural” does not mean safe. Dosing is also difficult because a particular herb may be available in several different dosage forms (eg. dose. 55) or risk of excessive bleeding (see Chap. and strengths of active ingredients. Some products (eg. tablet. Thus. or increase risks of bleeding. general information about the use or nonuse of supplements is assessed. ✔ ✔ ✔ ✔ ✔ ✔ thought to interact adversely with prescribed drugs or particular client conditions. Contact: NCCAM Clearinghouse PO Box 8218 Silver Spring. Store herbal and dietary supplements out of the reach of children. This is not true. John’s wort) can interfere with or increase the effects of some drugs. garlic. 2. Failure to consider these variables may decrease therapeutic effects or increase risks of adverse effects to an unacceptable level. try to determine the name. echinacea. GENERAL PRINCIPLES OF DRUG THERAPY General Goals and Guidelines 1. The American Society of Anesthesiologists recommends that all herbal products be discontinued 2–3 weeks before any surgical procedure. valerian and St. • Teach clients about these products and their possible interactions with each other and with their prescription drugs (when such information is available). As a result. capsule. their effects are largely unknown and may be dangerous for some people because there is little reliable information about them. Most herbal and dietary supplements should be avoided during pregnancy or lactation and in young children. extract) with different amounts of active ingredients. For example. In fact. some supplements are known to increase blood pressure (see Chap. 3. affect blood pressure or heart rhythm. to reduce risks of severe adverse effects or drug–supplement interactions.CHAPTER 4 NURSING PROCESS IN DRUG THERAPY 59 CLIENT TEACHING GUIDELINES General Information About Herbal and Dietary Supplements ✔ Herbal and dietary products are chemicals that have druglike effects in people. especially when taken concurrently with other herbals. MD 20907-8218 Tel: 1-888-644-6226 Website: www. Drug therapy should be individualized. ginseng. the nurse can ask about the use of specific supplements that may interact with the drug group(s) discussed in that chapter. Inform health care providers when taking any kind of herbal or dietary supplement. depending on the soil. other perioperative medications. . For most products. little research has been done to determine either their benefits or their adverse effects. In this chapter. amounts. ✔ The safety and effectiveness of these products are not documented or regulated by laws designed to protect consumers. dietary supplements. frequency and duration of use. Many variables influence a drug’s effects on the human body. the types and amounts of ingredients may not be standardized or even identified on the product label. kava. or drugs. ephedra. gingko. Unfortunately. different brands of the same herb vary in the amounts of active ingredients per recommended dose. When taking herbal or dietary supplements. drugs usually should not be prescribed for trivial problems or problems for which nondrug measures are effective. components and active ingredients of plants can vary considerably. The goal of drug therapy should be to maximize beneficial effects and minimize adverse effects. Expected benefits should outweigh potential adverse effects. • Assessment guidelines. • End-of-chapter references. feverfew. With herbal medicines especially. Inappropriate use or taking excessive amounts may cause dangerous side effects. • One of the best sources of information is the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health. some have unknown effects when combined with anesthetics.nih.nccam. In addition.gov • Ask clients whether they use herbal medicines or other dietary supplements. ✔ The product label should also state specific percentages. follow the instructions on the product label. tea. In later chapters. 57). These products are often advertised as “natural. ✔ These products can be used more safely if they are manufactured by a reputable company that states the ingredients are standardized (meaning that the dose of medicine in each tablet or capsule is the same).” Many people interpret this to mean the products are safe and better than synthetic or man-made products. most products contain several active ingredients and it is often not known which ingredient has the desired pharmacologic effect.

For example. 2. What factors might you consider before questioning the physician regarding the dosage that was ordered? . Dermatologic drugs are often formulated in different salts and dosage forms. including the following: 1. Some drugs are not recommended for use in children.” Most drugs given to adults also are given to children. For many drugs. neonatal therapeutics are discussed further in Chapter 67. however. and therefore dosages have not been established. 3. 2. Also. and drug therapy is less predictable than in adults. and organ function. and nursing process guidelines apply. and general principles. infants (1 month to 1 year). However. and sodium salts are often used. vagina. When pediatric dosage ranges are listed in drug literature. For example. In drug literature. Nursing Notes: Apply Your Knowledge You are assigned to care for a low-birth-weight infant. multiple drugs are commonly used to treat severe hypertension or serious infections. which also promotes compliance. Pharmacists and chemists choose salts on the basis of cost. manufacturers’ literature states that “safety and effectiveness for use in children have not been established. Body surface area. taste is a factor with oral drugs. clients with severe kidney disease often need much smaller doses of renally excreted drugs. weight. developmental level. the physician may order a limited number of relatively large (loading) doses followed by a regular schedule of smaller (maintenance) doses. Choice of drug is often restricted because many drugs commonly used in adult drug therapy have not been sufficiently investigated to ensure safety and effectiveness in children. however. Drug Therapy in Children Drug therapy in neonates (birth to 1 month). Drug effects on quality of life should be considered in designing a drug therapy regimen. and children (approximately 1 to 12 years) requires special consideration because of the child’s changing size. For example. Additional principles and guidelines include the following: 1. solubility. In general. including hazardous drug–drug interactions. application to intact skin or the mucous membranes of the eye. Although individual drugs allow greater flexibility of dosage than fixed-dose combinations. they are expressed in the amount of drug to be given per kilogram of body weight or square meter of body surface area. based on General Drug Selection and Dosage Considerations Numerous factors must be considered when choosing a drug and dosage range for a particular client. give the non-opioid drug if it is effective in relieving pain. Neonates are especially vulnerable to adverse drug effects because of their immature liver and kidney function. different salts of the same drug rarely differ pharmacologically. The least amount of the least potent drug that yields therapeutic benefit should be given to decrease adverse reactions. mouth. All aspects of pediatric drug therapy must be guided by the child’s age. A drug can be started rapidly or slowly. many of the combination products are formulated to be long acting. Clark’s rule is based on weight and is used for children at least 2 years of age: Weight (in pounds) × adult dose = child’s dose 150 b.60 SECTION 1 INTRODUCTION TO DRUG THERAPY 4. Safe therapeutic dosage ranges are less well defined for children than for adults. Calculating dosage based on body surface area is considered a more accurate method than those based on other characteristics. fixed-dose combinations are increasingly available and commonly used. 6. 5. Physiologic differences alter drug pharmacokinetics (Table 4–2). There are notable exceptions to this basic rule. techniques of drug administration. Most drug use in children is empiric in nature because few studies have been done in that population. nose. 4. For the most part. these should be used. mainly because clients are more likely to take them. and stability. and the amount needed for a specific dose must be calculated as a fraction of the adult dose. doses for children are extrapolated from those established for adults. When drug actions are not urgent. If it has a long half-life and optimal therapeutic effects do not usually occur for several days or weeks. Minimizing the number of drugs and the frequency of administration increases client compliance with the prescribed drug regimen and decreases risks of serious adverse effects. solubility is especially important with parenteral drugs. clients with serious illnesses may require larger doses of some drugs than clients with milder illnesses. recommended dosages are listed in amounts likely to be effective for most people. with expectations of measurable improvement as a result of drug therapy. therapy may be initiated with a maintenance dose. or rectum). and level of growth and development. The digoxin dosage seems very low to you. For example. if a mild non-opioid and a strong opioid analgesic are both ordered. convenience. Quality-of-life issues are also being emphasized in research studies. according to their intended uses (eg. For many drugs. who has been started on digoxin to treat congenital heart problems until corrective surgery can be performed. Hydrochloride. Often. use as few drugs in as few doses as possible. 3. sulfate. they are only guidelines to be interpreted according to the client’s condition. The following methods are used for these calculations: a.

Although age in years is an important factor. Physiologic Characteristics Increased thinness and permeability of skin in neonates and infants Immature blood–brain barrier in neonates and infants Increased percentage of body water (70% to 80% in neonates and infants. Responses also differ in the same person over time. older adults are quite heterogeneous in their responses to drug therapy and responses differ widely within the same age group.” Drug Therapy in Older Adults Aging is a continuum. including nonprescription drugs. out of reach of children. This would seem to indicate a need for larger doses. height and weight. Increased capacity for biotransformation of some drugs. Additional principles include the following: 1. Medications—both prescription and nonprescription drugs—should be taken only when necessary. Overall. prolonged drug half-life and decreased rate of drug clearance may offset. 2. when it reaches adult levels Decreased glomerular filtration rate in neonates and infants. It may be difficult to separate the effects of aging from the effects of disease processes or drug therapy. Any prescriber should review current medications. Use the oral route of drug administration when possible. corticosteroids may be absorbed sufficiently to suppress adrenocortical function) Increased distribution of drugs into the central nervous system because myelinization (which creates the blood–brain barrier to the passage of drugs) is not mature until approximately 2 years of age Usually increased volume of distribution in infants and young children. 6. For example. slowed excretion of drugs eliminated by the kidneys. diazepam (Valium). compared with adults. the goal of drug therapy may be “care” rather than “cure. and difficulty in complying with drug orders. Infants. In this population. phenobarbital. Drugs with decreased protein binding in neonates. pathologic changes due to disease processes. compared with 50% to 60% in children older than 2 years of age and adults) Altered protein binding until approximately 1 year of age. As a result. Use the estimated body surface area in the following formula to calculate the child’s dose: Body surface area (in square meters) 1. theophylline is cleared about 30% faster in a 7-year-old child than in an adult and approximately four times faster than in a neonate. salicylates (eg. This occurs because older adults are usually less able to metabolize and excrete drugs efficiently.” with efforts to prevent or control symptoms and maintain the client’s ability to function in usual activities of daily living. adverse effects are likely because of physiologic changes associated with aging (Table 4–3). However. In addition. and Children: Physiologic Characteristics and Pharmacokinetic Consequences Pharmacokinetic Consequences Increased absorption of topical drugs (eg. others). and theophylline (Theolair). never force oral medications because forcing may lead to aspiration. Decreased activity of liver drug-metabolizing enzyme systems in neonates and infants Increased activity of liver drug-metabolizing enzyme systems in children Decreased capacity for biotransformation of drugs. compared with older children and adults. If intramuscular injections are required in infants. aspirin). These doses can be used initially and then increased or decreased according to the child’s response. In neonates and infants. particularly long-term drug therapy. Iidocaine (Xylocaine). with increased risks of drug accumulation and adverse effects. general nursing process guidelines and principles of drug therapy apply. Dosage of these drugs may need to be decreased. but in this book people 65 years of age and older are so categorized.CHAPTER 4 NURSING PROCESS IN DRUG THERAPY 61 TABLE 4–2 Neonates. include ampicillin (Omnipen. compared with older children and adults. This results in a rapid rate of metabolism and elimination. before prescribing . 3. Kidney function develops progressively during the first few months of life and is fairly mature by 1 year of age. multiple drug therapy for acute and chronic disorders. depending on the infant’s age and level of growth and development. use the thigh muscles because the deltoid muscles are quite small and the gluteal muscles do not develop until the child is walking. keep all medications in childproof containers. This may result in a greater proportion of unbound or pharmacologically active drug and greater risks of adverse drug effects. 4. The amount and binding capacity of plasma proteins may be reduced. is estimated using a nomogram (Fig. precisely when a person becomes an “older adult” is not clearly established. Dosage requirements may be decreased or modified by other factors. Dosages obtained from these calculations are approximate and must be individualized. 4. organ function) is more important than chronologic age. phenytoin (Dilantin). Symptoms attributed to aging or disease may be caused by medications. drugs are more likely to accumulate. 4–1). This results in slowed metabolism and elimination. The net effect is often a need for decreased dosage. 5. impaired memory and cognition. and do not refer to medications as “candy. nafcillin (Unipen). For safety. digoxin (Lanoxin). Try to obtain the child’s cooperation.73 square meters ( m 2 ) × adult dose = child’s dose c. Physiologic age (ie.

especially with long-term use. The nurse gives Jamie 30 cc of amoxicillin for his morning dose.00 1. The amoxicillin is supplied in syrup containing 100 mg/10 cc. 7.35 1.8 3' 34" 32" 30" 28" 26" 2' 22" 20" 18" 16" 14" 1' 10" 9" 8" 20 25 0.80 2.10 1. This interval is not established for most drugs.60 20 Figure 4–1 Body surface nomograms. The basic principle of giving the smallest effective number of drugs applies especially to older adults.70 0.00 0. When drug therapy is required.95 1.75 0.3 50 45 40 35 0. or other aspects need to be revised.30 1.90 2.60 1. the choice of drug should be based on available drug information regarding effects in older adults.15 1.7 0. When any drug is started.20 2. This allows less disruption of usual activities and promotes compliance with the prescribed regimen.10 2.95 0. regimen of several drugs increases the incidence of adverse reactions and potentially hazardous drug interactions. The point at which this line intersects the middle vertical scale represents the client’s surface area in square meters (Courtesy of Abbott Laboratories). unnecessary drugs should be discontinued. To determine the surface area of the client.65 1. All drugs should be given for the shortest effective time.65 0.1 95 90 85 80 75 70 65 60 55 0.70 1. the dosage should usually be smaller than for younger adults.20 1.50 1. need to be tapered in dosage and discontinued gradually to avoid withdrawal symptoms. increments should be .90 0.30 2.85 1.85 0. to be administered q8h in equally divided doses Jamie weighs 10 kg and the recommendations for infants are 20–40 mg/kg/day. A How Can You Avoid This Medication Error? Amoxicillin is prescribed for Jamie for an ear infection.90 1.40 1. new drugs.80 0. many older adults are unable to self-administer more than three or four drugs correctly.6 0. draw a straight line between the point representing his or her height on the left vertical scale to the point representing weight on the right vertical scale.45 1. Health care providers must reassess drug regimens periodically to see whether drugs.75 1.25 1. 6. 8. In addition.62 SECTION 1 INTRODUCTION TO DRUG THERAPY Nomogram for estimating the surface area of infants and young children Height feet centimeters Nomogram for estimating the surface area of older children and adults Height feet centimeters Surface area in square meters Weight pounds 65 60 55 50 45 40 35 15 7' 10' 8' 6' 4' 2' 6' 10' 8' 6' 4' 2' 5' 10' 8' 6' 4' 2' 4' 5 10' 8' 6' Surface area in square meters Weight pounds 440 420 400 380 360 340 320 300 290 280 270 260 250 240 230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 30 60 25 50 kilograms 30 25 20 kilograms 200 190 180 170 160 150 140 130 120 110 100 95 90 85 80 75 70 65 60 55 50 45 40 35 0. and many drugs are continued for years. The smallest number of effective doses should be prescribed.40 2.4 20 10 15 5 0. The dosage can then be increased or decreased according to response. This is especially important when a serious illness or significant changes in health status have occurred.05 1.80 1. 5.00 2.70 2. The order is for 300 mg daily.50 2. 9.2 10 4 220 215 210 205 200 195 190 185 180 175 170 165 160 155 150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 30 3 2 4 3 4' 2' 1 3' 10' 8' 6' 3.60 2.5 30 25 0. Some drugs.55 1. In addition. dosages. If an increased dosage is indicated.

Use nondrug measures to decrease the need for drugs and to increase their effectiveness or decrease their adverse effects. pharmacologically active drug. d. decreased glomerular filtration rate. steroids) does not change significantly with aging). calcium channel blockers. c. with increased risks of drug accumulation and toxic effects. • Impaired drug excretion. acetaminophen. They may then be ignored or treated by prescribing a new drug. As above. antimicrobials. b. A magnifying glass also may be useful. In addition. subcutaneous or muscle tissue). go slow. If vision is impaired. the drug also may be metabolized and excreted more rapidly. Slowed metabolism and detoxification of many drugs. Decreased availability of protein for binding and transporting drug molecules. Also available are drug containers with doses prepared and clearly labeled as to the day and time each dose is to be taken. by avoiding caffeine-containing beverages and excessive napping) is much safer than taking sedative-hypnotic drugs. consider the possibility of adverse drug effects. when stopping or reducing the dose of an old drug is the indicated intervention. insomnia is a common complaint among older adults. including beta blockers. When renal blood flow is decreased. decreased number of functioning nephrons. drug interactions occur with co-administration of multiple drugs that are highly protein bound. morphine. Several devices may be used to schedule drug doses and decrease risks of omitting or repeating doses. Drug Therapy in Renal Impairment Many clients have or are at risk for impaired renal function. the statin cholesterol-lowering drugs. safe approach is sometimes called “start low.” 10. lithium) are distributed into a smaller area. 12. Preventing it (eg. accumulate in fat. effects on absorption from skin and mucous membranes are unknown • Decreased distribution to sites of action in tissues. gastrointestinal tract. For example. warfarin). Enlist family members or friends when necessary. a. new signs and symptoms are attributed to aging or disease. or administration of nephrotoxic drugs. avoid childproof containers for an older adult with arthritic hands. aspirin. hypertension. especially for those that are normally highly protein bound (eg. which may lead to drug accumulation and increased risks of adverse or toxic effects Water-soluble drugs (eg. (Numerous drugs metabolized by the CYP enzymes are often prescribed for older adults. and decreased tubular secretion smaller and made at longer intervals in older adults. calendars. Renal mass is also decreased and older adults may be more sensitive to drugs that further impair renal function (eg. Often. with resultant higher plasma concentrations and higher risks of toxicity with a given dose. label drug containers with large lettering for easier readability. Metabolism of drugs metabolized by conjugative reactions (eg. For people receiving long-term drug therapy at home. The drugs compete for protein-binding sites and are more likely to cause adverse effects with decreased levels of serum albumin. and antiulcer drugs. less drug is delivered to the kidney for elimination. Physiologic Characteristics Decreased gastrointestinal secretions and motility Decreased cardiac output Decreased blood flow to the liver and kidneys Decreased total body water and lean body mass per kg of weight. This increases serum concentration of free. prolonged half-life. thereby offsetting at least some of the risks. the client can tell at a glance whether a dose has been taken. major surgery or trauma. effects on extended-release formulations are unknown • Slower absorption from some sites of administration (eg. nonsteroidal anti-inflammatory drugs such as ibuprofen. With the latter system. and have a longer duration of action in the body. with potential for delaying the onset and reducing the extent of therapeutic effects Delayed metabolism and excretion. However. the result is larger concentrations of free drug. Be sure the client can open drug containers. diazepam) are distributed to a larger area. 11. When a client acquires new symptoms or becomes less capable of functioning in usual activities of daily living. increased body fat Decreased serum albumin Decreased blood flow to the liver. Clients with disease processes such as diabetes. ethanol. and this may be worsened by illness. Fat-soluble drugs (eg. or heart failure may have renal insufficiency on first contact.CHAPTER 4 NURSING PROCESS IN DRUG THERAPY 63 TABLE 4–3 Older Adults: Physiologic Characteristics and Pharmacokinetic Consequences Pharmacokinetic Consequences Minimal effects on absorption of most oral drugs. and increased risks of toxicity • Age-related alterations in renal function are consistent and well described. For example. In clients with nor- . use measures to help them take drugs safely and effectively. and charts. This may increase risks of adverse effects. diazepam. decreased number and activity of the cytochrome P450 (CYP) oxidative drug-metabolizing enzymes Decreased blood flow to the kidneys. which older adults often take for pain or arthritis). decreased size of the liver. These include written schedules. This conservative.

a smaller dose or a longer interval between doses is recommended for clients with moderate (creatinine clearance 10 to 50 mL/minute) or severe renal insufficiency (creatinine clearance < 10 mL/minute). tetracyclines except doxycycline). shock due to sepsis or blood loss. others can be used if safety guidelines are followed (eg. there are no effective substitutes and nephrotoxic drugs must be given. Some drugs are contraindicated in renal impairment (eg. the most effective dosage adjustments are based on the client’s clinical responses and serum drug levels. If a client is oliguric (<400 mL urine/24 hours). Because these clients usually have diminished muscle mass. renal function may recover if the impairment is recognized promptly. which is then used to calculate creatinine clearance as a measure of the glomerular filtration rate (GFR). Advil). Chronic renal failure (CRF) usually results from disease processes that destroy renal tissue. fluoroquinolones. interfere with secretion of creatinine into kidney tubules. and medication dosages are adjusted according to the extent of renal impairment. loss of body fluids with blood loss. inadequate fluid intake. Acute renal failure (ARF) may occur in any illness in which renal blood flow or function is impaired. major surgery. and metabolic alterations) that affect renal function. Many commonly used drugs may adversely affect renal function. For some drugs. Estimations are less accurate for emaciated and obese clients and for those with changing renal function. increased blood urea nitrogen or increased serum creatinine (>2 mg/dL or an increase of ≥0. Some commonly used nephrotoxic drugs include aminoglycoside antibiotics. health care providers need to know and use these recommendations to maximize the safety and effectiveness of drug therapy. In some instances. 1. stable serum creatinine) and average muscle mass (for their age. Guidelines have been established for the use of many drugs. specific guidelines for particular drug groups are included in appropriate chapters. seriously impaired cardiovascular function. Some general guidelines are listed here. contributing factors are eliminated or treated effectively. Thus. effective treatment can help to conserve functioning nephrons and delay progression to end-stage renal disease (ESRD). For clients receiving renal replacement therapy (eg. Drug therapy must be especially cautious in clients with renal impairment because of the risks of drug accumulation and adverse effects.64 SECTION 1 INTRODUCTION TO DRUG THERAPY mal renal function. Drug selection should be guided by baseline renal function and the known effects of drugs on renal function. however. In relation to drug therapy. an erroneous value will be obtained. Because serum creatinine is determined by muscle mass as well as the GFR. and cisplatin. the serum creatinine measurement can- not be used as the sole indicator of renal function unless the client is a young. Estimations of creatinine clearance are more accurate for clients with stable renal function (ie.5 mg/dL over a baseline value of <3. well-nourished person with a sudden acute illness. including nonsteroidal anti-inflammatory drugs such as prescription or OTC ibuprofen (Motrin. the creatinine clearance should be estimated to be less than 10 mL/minute. illnesses and their physiologic changes (eg. or other conditions. hemodialysis or some type of filtration). hepatic. Serum creatinine is also a relatively unreliable indicator of renal function in elderly or malnourished clients. and digoxin. for example. amphotericin B. If ESRD develops. As a result. and the effects of various drugs on renal function. serum creatinine levels are increased without an associated decrease in renal function. avoiding dehydration). for many commonly used drugs. relatively healthy. 5. which include cimetidine and trimethoprim. diuretic drugs. nephrotoxic drugs. However. With CRF. monitoring serum drug levels and renal function tests. all health care providers need to be knowledgeable about risk factors for development of renal impairment. an adequate fluid intake is required to excrete drugs by the kidneys. Some drugs are excreted exclusively (eg. lithium) and most are excreted primarily or to some extent by the kidneys. they may have a normal serum level of creatinine even if their renal function and GFR are markedly reduced. This is usually determined by measuring serum creatinine. 3. Dosage of many drugs needs to be decreased in renal failure. hemodynamic. vomiting. With ARF. renal. aminoglycoside antibiotics. the treatment removes variable amounts of drugs that are . 2. These drugs. drug therapy must be individualized according to the extent of renal impairment. Drugs known to be nephrotoxic should be avoided when possible. when possible. or diarrhea) increase the risk of worsening renal impairment in clients who already have impairment or of causing impairment in those who previously had normal function. and height). renal failure may develop from depletion of intravascular fluid volume. Renal status should be monitored in any client with renal insufficiency or risk factors for development of renal insufficiency. If a fluctuating serum creatinine is used to calculate the GFR. as often occurs in acute illness. most cephalosporin antibiotics. regardless of the serum creatinine concentration. dialysis or transplantation is required. reducing dosage. Clients with renal impairment may respond to a drug dose or serum concentration differently than clients with normal renal function because of the physiologic and biochemical changes. Any factors that deplete extracellular fluid volume (eg. 4. In addition. Some medications can increase serum creatinine levels and create a false impression of renal failure. the major concern with renal impairment is the high risk of drug accumulation and adverse effects because the kidneys are unable to excrete drugs and drug metabolites. including aminoglycoside antibiotics. nephrologists should design drug therapy regimens.0 mg/dL). However. weight. When possible. Signs and symptoms of ARF include decreased urine output (<600 mL/24 hours).

Overall. isoniazid. Betaadrenergic blocking agents decrease hepatic blood flow by decreasing cardiac output. In relation to drug therapy. for the shortest effective time. more drug stays in the bloodstream longer. nurses in emergency departments often initiate and maintain treatment for several hours. theophylline. It is difficult to predict the effects of drug therapy because of wide variations in liver function and few helpful diagnostic tests. or life-threatening illness. serious. abnormal liver function test results may occur without indicating severe liver damage and are often reversible. 2. ketoconazole) inhibit hepatic metabo- lism of many coadministered drugs. drug distribution is usually increased because of less protein binding and increased extracellular fluid. phenytoin. a supplemental dose may be needed to maintain therapeutic blood levels of drug. Alcohol is toxic to the liver by itself and increases the risks of hepatotoxicity with other drugs. nausea. clients formerly cared for in . In addition to hepatotoxic drugs. Critically ill clients are at risk for multiple organ failure. The consequence may be toxicity from the inhibited drugs if the dose is not decreased. denotes the care of clients who are experiencing acute. Indicators of hepatic impairment include serum bilirubin levels above 4 to 5 mg/dL. Dosage should be reduced for drugs that are extensively metabolized in the liver because. liver enlargement) and abnormal results of laboratory tests of liver function (see 4. including cardiovascular. Drug Therapy in Hepatic Impairment Most drugs are eliminated from the body by hepatic metabolism. increasingly. lorazepam. Fortunately. elimination is slower. they should be used in the smallest effective doses. Although blood volume is often decreased. many other drugs can cause or aggravate liver impairment by decreasing hepatic blood flow and drug-metabolizing capacity. hepatitis. Some drugs whose dosages should be decreased in hepatic failure include cefoperazone. below). cirrhosis) and those with disease processes that impair blood flow to the liver (eg. If they cannot be avoided. renal excretion. especially when clients are receiving potentially hepatotoxic drugs. and elevated serum alanine (ALT) and aspartate (AST) aminotransferases. ranitidine. epinephrine and related drugs may cause vasoconstriction in the hepatic artery and portal vein.0 g/dL. Hepatic metabolism depends mainly on blood flow and enzyme activity in the liver and protein binding in the plasma. intestine.CHAPTER 4 NURSING PROCESS IN DRUG THERAPY 65 usually excreted through the kidneys. shock. During drug therapy. and. a serum albumin below 2. if doses are not reduced. 3. lungs) may become more important in eliminating drugs from the body. morphine. and hepatic impairments that influence all aspects of drug therapy. In some clients. For example. with severe hepatic impairment. kidneys. nurses on other hospital units care for clients who are transferred to or from ICUs. nurses in numerous other settings also care for these clients.5 times control. major surgery. Some general guidelines for increasing drug safety and effectiveness are listed here. such as many antimicrobials. heart failure. Drug Therapy in Critical Illness The term critical illness. and cholesterol-lowering statins. guidelines for drug selection. some oral drugs are normally extensively metabolized during their “first pass” through the liver. and verapamil. known guidelines for particular drug groups are included in appropriate chapters. Although critical care nursing is a specialty area of practice and much of critical care is performed in an intensive care unit (ICU). An additional factor is hepatotoxic drugs. critically ill clients exhibit varying degrees of organ dysfunction and their conditions tend to change rapidly. cimetidine. and toxicity is more likely to occur in a client with hepatic disease. fluoxetine. Several drugs (eg. If blood flow is impaired so that lidocaine molecules in the blood are unable to reach drug-metabolizing liver cells. Liver function tests should be monitored in clients with or at risk for liver impairment. vomiting. whereas chronic cirrhosis or severe liver impairment may affect all pharmacokinetic processes. or both. quinidine. so that a relatively small portion of an oral dose reaches the systemic circulation. clients with impaired liver function require close monitoring for signs and symptoms (eg. the blood carrying the drug molecules is shunted around the liver so that oral drugs go directly into the systemic circulation. Drug elimination is usually impaired because of decreased blood flow and decreased function of the liver and kidneys. Commonly used hepatotoxic drugs include acetaminophen. With some drugs. jaundice. it has a great capacity for cell repair and may be able to function with as little as 10% of undamaged hepatic cells. the two main sources of the liver’s blood supply. clindamycin. With cirrhosis. as used here. 1. or trauma) or hepatic enzyme production. although the liver is often damaged. extrahepatic sites of drug metabolism (eg. a prothrombin time greater than 1. lidocaine is normally rapidly deactivated by hepatic metabolism. so that drug pharmacokinetics and pharmacodynamics vary widely. dosage. Clients at risk for impaired liver function include those with primary liver disease (eg. acute liver impairment may interfere with drug metabolism and elimination. diazepam. 4. Hepatotoxic drugs should be avoided when possible. For example. cimetidine. Drug selection should be based on knowledge of drug effects on hepatic function. Also. serum drug levels are higher. propranolol. meperidine. Thus. labetalol. and duration of use are not well established. For example. In addition. renal.

both of which affect the pharmacokinetics of the drugs administered. rapid drug action. In addition. impaired function of the GI tract. For clients with hypotension and shock. renal. Weigh clients when possible. However. may decrease absorption of other drugs. drugs usually should not be given orally. and the kidneys cannot excrete drugs effectively. and that maintenance dosages are titrated according to client responses and changes in organ function (eg. gastrostomy. especially cardiovascular. and metabolic alterations) that can be caused by the illnesses. initially and periodically. 3. distribution to body cells is unpredictable. safe and effective drug therapy requires that all involved health care providers be knowledgeable about common critical illnesses. periodic weights help to assess clients for loss of body mass or gain in body water. increasing numbers of nursing students are introduced to critical care during their educational programs. 1. because dosage of many drugs is based on weight. and transdermal medications may be used effectively in some critically ill clients. cardiovascular and central nervous system (CNS) effects may be faster. all nurses need to know about drug therapy in critically ill clients. and sedatives. many factors may interfere with drug effects (eg. few drugs are available in these formulations. In addition. it is especially important that initial dosages are individualized according to the severity of the condition being treated and client characteristics such as age and organ function. more pronounced. In many instances. Most drugs are given intravenously (IV) because critically ill clients are often unable to take oral medications and require many drugs. large doses. liver. 7. hemodynamic. As a result. 9. antiulcer drugs. If the drug is a sedative. in long-term care facilities. the liver cannot metabolize drugs effectively. it reaches the heart and brain quickly because the sympathetic nervous system and other homeostatic mechanisms attempt to maintain blood flow to the heart and brain at the expense of blood flow to other organs such as the kid- 6. and skin. symptoms. Dosage requirements may vary considerably among clients and within the same client at different times during an illness. Once-daily drug doses should be given at approximately the same time each day. gastrointestinal (GI) tract. Drugs used in critical illness represent most drug classifications and are also discussed in other chapters. intramuscularly. neuromuscular blocking agents. or liver) and drug–drug and drug–diet interactions may occur if precautions are not taken. hepatic. and relatively large doses. Overall. the goal of drug therapy is to support vital functions and relieve life-threatening symptoms until healing can occur or definitive treatment can be instituted. and less predictable than in most other populations. Thus. this is probably the preferred route. For clients who receive oral medications or nutritional solutions through a nasogastric. Drug selection should be guided by the client’s clinical status (eg. more problematic. kidneys. subcutaneously. effects may include excessive sedation and cardiac depression. the IV route achieves more reliable and measurable blood levels. and combinations of highly potent medications. or jejunostomy tube. cardiovascular agents. gastric acid suppressants. the timing of administration may be important in increasing therapeutic effects and decreasing adverse effects. Sublingual. multiple-daily doses should be given at approximately even intervals around the clock. Moreover. and experienced nurses may transfer to an ICU. 5. If the client is able to take oral medications. or even at home. heart. as indicated by symptoms or laboratory tests). and longer lasting than usual. renal. severity of illness) and organ function. 2. or by skin patch because shock impairs absorption from their sites of administration. more specific guidelines related to particular drugs are included in the appropriate chapters. However. Laboratory tests are often needed before and during drug therapy of critical illnesses to assess the client’s . Route of administration should also be guided by the client’s clinical status. In addition. many new graduates seek employment in critical care settings. A standard dose may be effective. oral inhalation. the physiologic changes (eg.66 SECTION 1 INTRODUCTION TO DRUG THERAPY an ICU are on medical-surgical hospital units. 4. subtherapeutic. Some general guidelines to increase safety and effectiveness of drug therapy in critical illness are listed here. Nurses need to be especially diligent in administering drugs and vigilant in observing client responses. Drug therapy in clients who are critically ill is often more complex. When a drug is given IV. and the drugs used to treat the illnesses. neys. which are often given to prevent stress ulcers and GI bleeding. For example. In this at-risk population. Another reason is that critically ill clients often require aggressive treatment with large numbers. or toxic. antimicrobials. One reason is that clients often have multiple organ impairments that alter drug effects and increase the risks of adverse drug reactions. therapeutic effects may be decreased and risks of adverse reactions and interactions may be increased because the client’s body may be unable to process or respond to drugs effectively. crushing tablets or opening capsules to give a drug by a GI tube may alter the absorption and chemical stability of the drug. there may be drug–food interactions that impair drug absorption. Commonly used drugs include analgesics. and hepatic functions. 8. With many drugs. Thus.

is often required during follow-up. risk of infection with corticosteroids and other immunosuppressants. duration of use. electronic mail may be a convenient and efficient method of communication. 3. 10. With this information. blood levels are higher and may cause adverse effects. whether a tablet can be crushed. Home Care Home care is an expanding area of health care. Serum protein levels should be monitored in critically ill clients because drug binding may be significantly altered. Establish a method for contact in case the appointment must be canceled by either party. If there is not enough albumin to bind a drug. Alpha1-acid glycoprotein binds basic drugs and its synthesis may increase during critical illness. the nurse may initially need to demonstrate administration or coach the client or caregiver through each step. such as managing medication regimens. Most people are accustomed to taking oral drugs. and perceived beneficial or adverse effects. imipramine. lidocaine) and therapeutic blood levels may not be achieved unless higher doses are given. The results of these tests may indicate that changes are needed in drug therapy. elicit cooperation. try to determine the amount. With other routes. Assess the client’s attitude toward the prescribed medication regimen and his or her ability to provide self-care. and provide reassurance. these drugs are eliminated more slowly than usual. side effects. Clients may require short. is usually decreased during critical illness for a variety of reasons. Provide whatever information and assistance is needed for home management of the drug therapy regimen. the nurse may be able to reinforce the client’s compliance or identify potential problem areas (eg. Other tests may include measurement of serum drug levels. Some additional principles and factors include the following: 1. As a result. In both instances. identify problems. but they may need information about timing in relation to food intake. clients of all age groups are often discharged to their homes for follow-up care and recovery. propranolol.CHAPTER 4 NURSING PROCESS IN DRUG THERAPY 67 condition (eg. In addition to safe and accurate administration. especially the costs of hospitalization. and other aspects. risk of falls and other injuries with opioid analgesics and other drugs with sedating effects). teach the client and caregiver to observe for beneficial and adverse effects. continued use of medications that were supposed to be discontinued. Ask if the client takes any herbal medicines or dietary supplements. who will be the primary caregiver for medication administration and ob7. and so forth. when to omit the drug. The initial contact is usually by telephone. In most instances. Explain that the nurse needs this information because some herbals and dietary supplements may cause various health problems or react adversely with prescription or OTC medications. unbound molecules are metabolized and excreted more readily so that therapeutic effects may be decreased. The consequences of this trend include increased outpatient care and brief hospitalizations for severe illness or major surgery. 4.or long-term drug therapy. drugs with opposing or duplicate effects. or manipulating an intravenous infusion pump. state the main purpose of the visit and approximately how long the visit will be. In a client’s home. Assess the environment for potential safety hazards (eg. the home care nurse can maintain contact with clients and caregivers to monitor progress. assess the client’s ability to obtain medications and keep appointments for followup visits to health care providers. If the client is unable. For clients and nurses with computers and Internet access. teach them how to manage minor ones and which ones to report to a health care provider. If side effects occur. including inadequate production by the liver. preferably at a convenient time for the client and caregiver. 5. Most general principles and nursing responsibilities related to drug therapy apply in home care as in other health care settings. Skilled nursing care. This trend evolved from efforts to reduce health care costs. Serum albumin. The nurse may wish to schedule a daily time for receiving and making nonemergency calls. and ask how and when the client takes each one. cardiovascular. preparing and administering an injection. and one purpose is to schedule a home visit. If so. differences between instructions and client usage of medications. 2. fluid and electrolyte balance) and response to treatment. answer questions. the nurse is a guest and must work within the environment to establish rapport. and provide nursing care. In addition. the role of the nurse is to teach the client or caregiver to administer medications and monitor their effects. meperidine. Demonstrating and having the client or caregiver do a return demonstration is a good way to teach psychomotor skills such as giving a medication through a GI tube. Between home visits. which binds acidic drugs such as phenytoin and diazepam. reasons for use. In addition. drugs discontinued because of adverse effects). serving for medication effects? What are the learning needs of the client or caregiver in relation to the medication regimen? Ask to see all prescribed and OTC medications the client takes. In addition. 8. . 6. Also. Clients and caregivers should be given a telephone number to call with questions about medications. 9. the bound portion of a dose increases for some drugs (eg. frequency. renal and hepatic functions.

and those receiving large doses of any drug. The time may vary by approximately 30 minutes. Assemble appropriate supplies and equipment. d. Observe for adverse effects. Commonly needed reports include serum potassium levels before giving diuretics. 1. Check blood pressure (recent recordings) before giving antihypertensive drugs. Practice the five rights of drug administration (right drug. do not give antacids with any other oral drugs. This is often needed to look up new or unfamiliar drugs. Antacids decrease absorption of many oral drugs. e. If noted. In general. Follow label instructions regarding mixing or other aspects of giving specific drugs. although the incidence and severity of adverse reactions vary among drugs and clients. laboratory or other diagnostic test reports. Observe for therapeutic effects. For example. a. Specific observations depend on the specific drug or drugs being given. Is it contraindicated? Is it likely to interact with other drugs the client is taking? Does the client’s ordered dose fit within the dosage range listed in the drug reference? Can a tablet be crushed or a capsule opened without decreasing therapeutic effects or increasing adverse effects?) These rights are ensured if the techniques described in Chapter 3 are consistently followed. d. Compare results. 2. a. Check temperature before giving an antipyretic. If unsure about the results. administer at least 2 hours apart. complete blood count [CBC]. the nurse should know the expected effects and when they are likely to occur. 2. c. Administer drugs accurately (see Chap. b. those taking several drugs. Check laboratory (eg. ask a colleague or a pharmacist to do the calculation. right client. Except for very simple calculations. Check drug references when indicated. Use correct techniques for different routes of administration. a drug ordered for 9 AM can be usually given between 8:30 AM and 9:30 AM. right dose. In general.68 SECTION 1 INTRODUCTION TO DRUG THERAPY NURSING ACTIONS NURSING ACTIONS Monitoring Drug Therapy RATIONALE/EXPLANATION If giving medications to a group of patients. Accuracy is vital. All drugs are potentially harmful. For example. liver function tests) and other diagnostic test reports for abnormal values. and right time). Look for signs and symptoms of new problems or worsening of previous disorders. Check laboratory reports when indicated. People most likely to have adverse reactions are those with severe liver or kidney disease. Some drugs require specific techniques of preparation and administration. Specific adverse effects for which to observe depend on the drugs being given. Ask questions to determine whether the client is feeling better. (continued ) . No variation is allowed in the other rights. or ability to function. Calculate doses when indicated. Prepare medications for administration. right route. b. start preparing about 30 minutes before the scheduled administration time when possible. use pencil and paper to decrease the risk of errors. Look for improvement in signs and symptoms. b. electrolytes. c. sterile equipment and techniques are required for injection of any drug. culture and susceptibility reports before giving an antibiotic. Medications and supplies are usually kept on a medication cart in a hospital or long-term care facility. a. When both are ordered. b. to avoid rushing and increasing the risk of errors. Check vital signs when indicated. those who are very young or very old. prothrombin time or international normalized ratio (INR) before giving Coumadin. blood urea nitrogen and serum creatinine. a. 3. other uses include assessing a drug in relation to a particular client (eg. 3). compare the client’s symptoms with your knowledge base about adverse effects associated with the drugs or consult a drug reference.

7. For older adults. b. The review of natural products. It is never wrong to discuss your concerns with the physician. Journal of the Americal Pharmaceutical Association. With children. How Can You Avoid This Medication Error? Answer: The nurse administered the wrong dose of medication to Jamie. what are some potential difficulties with drug administration. and what information should usually be included? 8. explain what is meant by “start low. Louis: Facts and Comparisons. how can the nurse evaluate whether they are safe or unsafe in view of the client’s condition and drug therapy regimen? Nursing Notes: Apply Your Knowledge Answer: With infants. R. Springhouse. 234–242. to start drug doses low and increase if necessary. 4. 3. Why do nurses need to know the therapeutic and adverse effects of the drugs they give? 2. (2000). Thirty cc would provide the entire daily dose of amoxicillin. A. J. d. Anticipate the questions a client might ask about a drug and rehearse possible answers. a. 257–269. warfarin. excretion is reduced because the liver and kidneys are often immature in the low-birth-weight infant. causing toxicity. worsening congestive heart failure). It is prudent. Carefully reread the order and recalculate the dosage ordered. L. & Avila. Given a newly assigned client. and how can they be prevented or minimized? 5. (1999). Professional’s handbook of complementary & alternative medicines. This is especially true for a drug like digoxin that has a narrow therapeutic range. If noted. especially if your assessment reveals that therapeutic effects have not occurred (eg. I. Why is client teaching about drug therapy needed. 9. SELECTED REFERENCES Review and Application Exercises 1. what are some likely differences between the nursing care needed by a child and an adult? 10. Look for signs and symptoms of new problems or worsening of previous ones. Describe at least three important nursing considerations for clients who have renal or hepatic impairment or critical illness. including drugs that are well known to you and those that are not. Assess for decreasing ability to function at previous levels. For a client who reports using particular herbal or dietary supplements. sedatives. & Nace. . DerMarderosian. it is helpful to build a knowledge base about important interactions with commonly used drugs (eg. 4.) (2001). Ask questions to determine how the client is feeling and whether he or she is having difficulties that may be associated with drug therapy. and how can they be prevented or minimized? 6. Although no one can be expected to know or recognize all potential or actual interactions. Fetrow. Hardy. Decreased protein binding may result in higher blood levels of digoxin. With older adults. M. especially low-birth-weight infants. Also. compare the client’s symptoms with your knowledge base about interactions associated with the drugs or consult a drug reference to validate your observations. J.CHAPTER 4 NURSING PROCESS IN DRUG THERAPY 69 NURSING ACTIONS c. 20(3). M. what are some potential difficulties with drug administration. (Ed. PA: Springhouse Corp. cardiovascular drugs). what information is needed about present and previous medications or herbal and dietary supplements? Boullata. W. For the home care nurse assisting with a medication regimen. Consider a possible interaction when a client does not experience expected therapeutic effects or develops adverse effects. rather than 100 mg. go slow” and why it is a good approach to drug therapy. 40(2). Women’s Health series: Herbs of special interest to women. which should be administered every 8 hours. the danger of potential drug toxicity is high. Safety issues with herbal medicine. C. Unit dosing can help double–check calculations and avoid errors. Pharmacotherapy. RATIONALE/EXPLANATION Interactions may occur whenever the client is receiving two or more drugs concurrently and the number of possible interactions is very large. especially with the very young and the very old. (2000). A. St. Observe for drug interactions.

D. The proverbial herb. (2000).tyle/sram0402. Tyler. KrishnaRaj. cost. Philadelphia: Lippincott Williams & Wilkins.02. 17–21. Miller.tyle.. Hummel.02.. Cauffield. J. Scientific Review of Alternative Med- icines. Scientific Review of Alternative Medicines. D. Chin. Three herbs you should get to know. L. 101(2). Alternative medicine: Prevalence. E. White paper on herbal products. Product definition deficiencies in clinical studies of herbal medicines. M. .html Accessed January. American Journal of Nursing. (2000).medscape. (2000). A. M. 101(4). Phytopharmaceuticals: Problems. 421—425.n02/sram0402... A. K.). A. 2001. 877–891. T. and usefulness.. Pharmacotherapy. 20(7). W. L.com/ prometheus/SRAM/2000/v04. J. 48–53.. M. Humes (Ed. 4th ed. [On-line]. American Journal of Nursing. In H.01. G. Metzl.. Humes (Ed. Hume. J. D. 319–323. S. & Knell. In H.medscape. (2001). Accessed January. Harris.).. pp. Philadelphia: Lippincott Williams & Wilkins.. 3095–3107. Kanmaz.murc01.com/prometheus/SRAM/2000/ v04.01. 2001. Available: http://www. E. S. & Saxena. 4th ed.. Multach. (2001). & Sumners. 108(2). V. and solutions. limitations.70 SECTION 1 INTRODUCTION TO DRUG THERAPY Hatcher. J.. (2000).html. J. & Levine.. 36–43. B. Geriatric clinical pharmacology. S. Pediatrics. Kelley’s Textbook of internal medicine. T. R. Waddell.n02/sram0402. 33–37. S. E. Small. Kelley’s Textbook of internal medicine. Murch. (2001). 4(2). Schwartz. (2000).murc/sram0402. M. T.. I. Creatine use among young athletes. Jackson.. E. P. pp.. 4(2). Available: http://www. [On-line]. D. F.

2 Drugs Affecting the Central Nervous System .

Describe the process of neurotransmission. a dendrite. A dendrite has a branching structure with many synapses or sites for receiving stimuli or messages. pain signals) are found together in a common pathway or tract. called ganglia or nuclei. both skeletal and smooth. knob-like structures called vesicles. the CNS constantly receives information about blood levels of oxygen and carbon dioxide. THE STUDENT WILL BE ABLE TO: 1. Characteristics that allow neurons to communicate with other cells include excitability (the ability to produce an action potential or be stimulated) and conductivity (the ability to convey electrical impulses). interpret. and receptors (described below). Many axons are covered by a fatty substance called myelin. Neurotransmitters Neurotransmitters are chemical substances that carry messages from one neuron to another. emotions can strongly influence neural control of body function. 3. 4. An axon is a finger-like projection that carries impulses away from the cell body. More specific components of the communication network include neurotransmitters. problem solving. and alterations in neural functions can strongly influence mood and behavior. the neuron is the basic functional unit. CHARACTERISTICS AND FUNCTIONS OF THE CENTRAL NERVOUS SYSTEM Neurons The CNS is composed mainly of two types of cells: the glia protect. These structures project into the synapse and contain the granules where neurotransmitters are stored. More specifically. They are . Nerve fibers involved in the transmission of the same type of impulses (eg. More specific characteristics are reviewed to aid understanding of drugs that act by altering CNS functions. A lack of coordination or imbalances among the components may lead to mental or physical disorders. thought. memory) and with muscle function. Discuss signs and symptoms of central nervous system (CNS) depression. composed of the brain and spinal cord. the vasomotor and respiratory centers in the medulla oblongata). and sensory stimuli and sends messages to effector organs to adjust the environment toward homeostasis. or from a neuron to other body tissues. efferent or motor neurons carry messages away from the CNS. Discuss general types and characteristics of CNS depressant drugs. Describe major neurotransmitters and their roles in nervous system functioning. acts as the control center for regulating physical and mental body processes. synapses. modify. and nourish the neuron. Although various components of brain function are often studied individually. This communication involves a complex network of electrical and chemical signals that receive. The central nervous system (CNS). Neurons must be able to communicate with other neurons and body tissues. reasoning. and components of the CNS have complex interactions with each other. Afferent or sensory neurons carry messages to the CNS. support. body temperature. learning. 2. it is the overall coordination of the “mind/body” connections that produces mental and physical health. Thus. Most neurons are composed of a cell 72 body. and an axon. which are then conducted toward the cell body. The myelin cover or sheath protects and insulates the axon. The CNS has complex interactions with other parts of the body. An axon together with its myelin sheath is called a nerve fiber. It is also concerned with higher intellectual functions (eg. The end of the axon branches into presynaptic fibers that end with small. and send messages. A cluster of cell bodies or nuclei with the same function is called a center (eg. Nerve cell bodies usually occur in groups or clusters. such as cardiac or skeletal muscle.chapter 5 Physiology of the Central Nervous System Objectives AFTER STUDYING THIS CHAPTER.

degradation. slowly acting neurotransmitters. hypoxia. or chemical. or destruction by enzymes (eg. for which specific characteristics and functions have not yet been delineated. For example. several subtypes have been identified. One factor is the availability of precursor proteins and enzymes required to synthesize particular neurotransmitters. If the Presynaptic nerve terminal SYNAPSE Release site Postsynaptic nerve terminal Receptor sites Neurotransmitters Presynaptic nerve cell membrane Postsynaptic nerve cell membrane Figure 5–1 Neurotransmission in the central nervous system. most receptors are on postsynaptic neurons. acetylcholine is degraded by cholinesterase. rapidly acting neurotransmitters. such as the neuropeptide hormones (eg. Another factor is the number and binding capacity of receptors in the cell membranes of presynaptic and postsynaptic nerve endings. and drugs. For most receptors. released by the presynaptic nerve. ADH) serve as chemical messengers in both the nervous system and the endocrine system. Some receptors act rapidly to open ion channels. norepinephrine and acetylcholine). Neurotransmitter molecules (eg. the amines (dopamine. Neurotransmitter release and removal occur in the synapses. A neurotransmitter– receptor complex may have an excitatory or inhibitory effect on the postsynaptic neuron. and peptides. In this case. Several factors affect the availability and function of neurotransmitters. and amino acids (aspartate. Most acute CNS responses are caused by small-molecule. norepinephrine. Receptors increase in number and activity (up-regulation) when there is underactivity at the synapse. Free neurotransmitter molecules (ie. others interact with a variety of intracellular proteins to initiate a second messenger system. Three main types of neurotransmitters are amines. which causes CNS depression (coma occurs within seconds without oxygen).or beta-adrenergic receptors. norepinephrine is metabolized by monoamine oxidase and catecholomethyl transferase). molecules of neurotransmitter cross the synapse. in which sodium and potassium ions can rapidly conduct an electrical impulse from one neuron to another. glutamate. adrenocorticotropic hormone [ACTH or corticotropin] and antidiuretic hormone [ADH]). Synapses may be electrical. When released from the synaptic vesicles. Receptors Receptors are proteins embedded in the cell membranes of neurons. intracellular events include activation of the enzyme adenyl cyclase and the production of cyclic adenosine monophosphate (cAMP). In the CNS. They decrease in number and activity (down-regulation) when there is overactivity. . and others.CHAPTER 5 PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM 73 synthesized and stored in presynaptic nerve terminals and released in response to an electrical impulse (action potential) arriving at the end of the first neuron (presynaptic fiber). Most prolonged CNS responses are caused by large-molecule. which may alter neurotransmitter synthesis. in which a neurotransmitter conducts the message to the next neuron. The entry of calcium ions is required for neurotransmitter release from storage sites in small sacs called synaptic vesicles. changes in activation or deactivation of specific genes in the cell nucleus. receptors are constantly being synthesized and degraded. amino acids. cross the synapse and bind with receptor proteins in the cell membrane of the postsynaptic nerve. when norepinephrine binds with alpha. serotonin). and excite or inhibit postsynaptic neurons. substance P. bind to receptors in the cell membrane of the postsynaptic neuron (Fig. More specifically. gamma-aminobutyric acid [GABA]. A neurotransmitter must bind to receptors to exert an effect on the next neuron in the chain. such as acetylcholine. Substance P plays a role in transmitting pain signals from peripheral tissues to the CNS and the stress response to noxious stimuli. Like other protein molecules in the body. it is believed that receptor proteins are constantly being formed by the endoplasmic reticulum–Golgi apparatus and inserted into presynaptic and postsynaptic membranes. and alterations in the numbers of excitatory or inhibitory postsynaptic membrane receptors. the cAMP is a second messenger that activates cellular functions and the physiologic responses controlled by the alpha.and beta-adrenergic receptors. but some are on presynaptic nerve terminals. Some peptides (eg. Prolonged effects are thought to involve closure of calcium channels. The basis for the action potential is the transient opening of ion channels. those not bound to receptors) are rapidly removed from the synapse by three mechanisms: transportation back into the presynaptic nerve terminal (reuptake) for reuse. Storage of neurotransmitters allows them to be available quickly when needed and to avoid degradation by enzymes in the nerve terminal. Other important factors include acid–base imbalances (acidosis decreases and alkalosis increases synaptic transmission). 5–1). or binding to receptors to cause either CNS stimulation or depression. all of which are derived from body proteins. The chemical synapse is more commonly used to communicate with other neurons or target cells. release. and glycine). diffusion into surrounding body fluids. Synapses Neurons in a chain are separated by a microscopic gap called a synapse or synaptic cleft. changes in cellular metabolism.

74 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM synapses are overused and excessive amounts of neurotransmitter combine with receptor proteins. GABAB has not been delineated. acetylcholine is associated with level of arousal. synapses. Repeated stimulation of dopamine receptors decreases their numbers (down-regulation) and their sensitivity to dopamine (desensitization). Dopamine is derived from tyrosine. dopamine actions at the cellular level depend on the subtype of receptor to which it binds and the simultaneous effects of other neurotransmitters at the same target neurons. D2 receptors have been described most thoroughly. The other group includes D2. suppress calcium ion currents. Acetylcholine exerts excitatory effects at synapses and nerve–muscle junctions and inhibitory effects at some peripheral sites. Dopamine makes up more than half the catecholamine content in the brain and is found in the substantia nigra. and D4 receptors. the effects of norepinephrine–alpha2 receptor coupling are thought to stem mainly from activation of receptor-operated potassium ion channels and suppression of voltage-operated calcium ion channels. the noradrenergic system is associated with mood. basal ganglia. in renal and mesenteric blood vessels. Dopamine also occurs outside the brain. GABA is synthesized in the brain (cerebellum. dopamine is thought to be inhibitory in the basal ganglia but may be excitatory in other areas. Thus. Two groups of dopamine receptors have been identified. Major neurotransmission systems are the cholinergic. D3. It is the major inhibitory neurotransmitter in the CNS. Neurotransmission Systems Neurons function through communication networks that may be called neurotransmission systems. it is inhibitory in a few areas because of inhibitory receptors at some nerve synapses. noradrenergic. including the reticular formation. such as organs supplied by the vagus nerve. but it is thought to function in the regulation of ion channels and biochemical pathways. When released. and receptors are discussed separately here. the effect is similar to that of a negative feedback system that inhibits the release of norepinephrine. 9) and Parkinson’s disease. Norepinephrine receptors in the CNS. Activation of alpha2 receptors is associated with inhibition of adenyl cyclase activity and decreased production of cAMP. The GABA-ergic system uses GABA as its neurotransmitter. and beta2 receptors is thought to stimulate activity of intracellular adenyl cyclase and the production of cAMP. These effects on ion channels may increase membrane resistance to stimuli and inhibit the firing of CNS neurons. Overall. and reward. the major elements of which are neurotransmitters. A and B. with high concentrations in the substantia nigra and basal ganglia. In the CNS. GABA-ergic. It is also a neurotransmitter in the autonomic nervous system and at peripheral neuromuscular junctions. . Some receptors (called autoreceptors) occur on the presynaptic nerve terminal. Prolonged blockade of dopamine receptors increases their numbers and sensitivity to dopamine. One group includes D1 and D5 receptors. and the hypothalamus. Activation of alpha1. D3 and D4 receptor functions have not been delineated. dopamine stimulates these receptors and a negative feedback system is initiated that inhibits further dopamine synthesis and release. regulation of arousal. and receptors. as in the sympathetic nervous system. The GABAA receptor is a chloride ion channel that opens when GABA is released from presynaptic neurons. memory. There is evidence of multiple subtypes of GABA receptors and important functional differences among them. Although many details of neuronal function remain elusive. during which dreaming occurs. motor conditioning. GABA receptors have been divided into two main types. and serotonergic networks. a great deal of knowledge has been gained. it is then postulated that many of the receptor proteins are inactivated and removed from the synaptic membrane. Although neurotransmitters. beta1. it is the interaction among these elements that promotes order or disorder in the body’s physical and mental processes. However. with especially high concentrations in the motor cortex and basal ganglia. numerous neurotransmitters and subtypes of receptors have been identified and characterized. They are differentiated by the intracellular events that follow dopamine–receptor binding. It is found in relatively large amounts in the hypothalamus and the limbic system and in smaller amounts in most areas of the brain. an amino acid. Much of the information about dopamine is derived from studies of antipsychotic drugs (see Chap. are divided into alpha. and activate potassium ion currents. For example. In addition. with a role in many neuronal circuits (estimated at nearly one third of CNS synapses). dopaminergic. The dopaminergic system uses dopamine as its neurotransmitter. Acetylcholine. norepinephrine is a catecholamine synthesized from tyrosine. synaptic fatigue and downgrading or upgrading of receptors work with other control mechanisms of the nervous system to readjust abnormally stimulated or depressed nerve function toward normal. they are thought to inhibit activation of adenyl cyclase and subsequent production of cAMP. alpha2 receptors on the presynaptic nerve ending are believed to regulate norepinephrine release. Norepinephrine is mainly an excitatory neurotransmitter that stimulates the brain to generalized increased activity. and is a precursor substance in the synthesis of norepinephrine and epinephrine. The cholinergic system uses acetylcholine as its neurotransmitter. a disorder caused by destruction of dopamine-producing neurons in the substantia nigra. motor activity. The noradrenergic system uses norepinephrine as its neurotransmitter and extends to virtually every area of the brain.and beta-adrenergic receptors and their subtypes. In other words. Like dopamine. and cerebral cortex) and spinal cord in abundant amounts. the first substance to be designated as a neurotransmitter in the CNS. In the CNS. and speech. the midbrain. when high levels of extracellular norepinephrine act on presynaptic alpha2 receptors. Overall. synapses. However. It is thought to play an important role in producing rapid-eyemovement (REM) sleep. which activate adenyl cyclase to produce cAMP. is located in many areas of the brain.

the resulting dysregulation and imbalances lead to signs and symptoms of CNS disorders. When abnormalities occur in any of these elements. beginning in the midbrain and projecting into the thalamus. most psychiatric symptoms result from CNS stimulation and usually involve physical and mental hyperactivity. CNS function in both health and disease is probably determined by interactions among neurotransmission systems. nervousness. the sleep–wake cycle. and sensory perceptions. for example. manifestations include unpleasant feelings of tension. In general. Aspartate is an excitatory neurotransmitter found in high concentrations in the brain. It may also be involved in the vascular spasm associated with some pulmonary allergic reactions (during which it is released from mast cells) and migraine headaches. subtypes have been identified but their functions are unknown. where increased release and impaired reuptake of glutamate lead to excessive stimulation of glutamate receptors and subsequent cell death. Except for mental depression. such as severe anxiety or psychosis. or hypoxia). In health. as well as the balance between excitatory and inhibitory forces. Glycine receptors have many of the features described for GABAA receptors. energy. Amino acids were recognized as neurotransmitters relatively recently. each with a unique distribution in the CNS. and decreased ability to rest and sleep. Events leading to neuronal death are triggered by excessive activation of NMDA receptors and movement of calcium ions into the neurons. during which it is released from platelets and causes vasoconstriction. dysfunction or destruction of the neurons that normally produce neurotransmitters. then. but research suggests that the N-methyl D-aspartate (NMDA) glutamate receptor subtype plays a role in memory. Insufficient amounts of inhibitory neurotransmitters (eg. complex mechanisms regulate the amounts and binding capacities of neurotransmitters and receptors. hyperarousal states. Neurotransmission Systems in Selected Central Nervous System Disorders Abnormalities in neurotransmission systems (eg. CNS serotonin is usually an inhibitory neurotransmitter and is associated with mood. the amount of tryptophan intake in the diet and the enzyme tryptophan hydroxylase control the rate of serotonin production. mainly in mast cells of the lungs and platelets. Such hyperactivity reflects a wide range of observable behaviors and nonobservable thoughts and feelings. habituation. psychomotor agitation. Activation of some receptors leads to hyperpolarization and neuronal inhibition. decreased acetylcholine is a characteristic of Alzheimer’s disease. neurotransmission systems function interdependently. Many psychiatric disorders. and Huntington’s disease. hypoglycemia. For example. Although most research has focused on single neurotransmitters and their respective receptors. GABA) 4. schizophrenia. excitatory neurotransmitters in the brain. Several subtypes of glutamate receptors have been identified. It occurs in high concentrations in virtually every area of the CNS.CHAPTER 5 PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM 75 The serotonergic system uses serotonin (also called 5-hydroxytryptamine or 5-HT) as its neurotransmitter. Serotonin is thought to produce sleep by inhibiting CNS activity and arousal. and drugs of abuse may cause varying degrees of CNS stimulation. cerebral cortex. manifestations may include pleasant feelings of mild euphoria and high levels of enthusiasm. or otherwise modify the effects of another system. the pathogenesis of excessive CNS stimulation may involve one or more of the following mechanisms: 1. GABA abnormalities occur in anxiety. stroke. In people with psychiatric illnesses. and hippocampus. some of which are linked to inhibition of adenyl cyclase activity or to regulation of potassium or calcium ion channels. Although some glutamate is apparently necessary for normal neurotransmission. Altered glutamate metabolism may also lead to the formation of free radicals. Glutamate is considered the most important excitatory neurotransmitter in the CNS. In most people. Excessive amounts of excitatory neurotransmitters (eg. brief exposure of neurons to high concentrations can lead to neuronal cell death. which are implicated in neuronal cell death associated with some neurodegenerative diseases and toxic chemicals. Increased numbers or sensitivity of excitatory receptors 3. Because serotonin is synthesized from the amino acid tryptophan. The functions of these receptor subtypes have not been established. including the cerebral cortex. It plays a major role in the blood coagulation process. and productivity. decrease. The amino acid system includes several amino acids that may serve as both structural components for protein synthesis and neurotransmitters. therapeutic drugs. limbic structures. hypothalamus. Several subtypes of serotonin receptors have been identified. and their roles and functions in this regard have not been completely elucidated. even when very tired. Overall. including some drugs of abuse. altered receptor response to neurotransmitters) are implicated in many CNS disorders. basal ganglia. However. and seizure disorders. from ischemia. Decreased numbers or sensitivity of inhibitory receptors . This process may be similar to the neurotoxicity as- sociated with brain injury (eg. dopamine abnormalities occur in psychosis and Parkinson’s disease. and spinal cord. Serotonin-synthesizing neurons are widely distributed in the CNS. including inhibition of pain pathways in the spinal cord. and serotonin abnormalities are thought to be involved in mental depression and sleep disorders. glutamate has been implicated in the pathogenesis of epilepsy. Aspartate and glutamate are considered the major fast-acting. Serotonin is also found outside the CNS. one system may increase. Glycine is an inhibitory neurotransmitter found in the brain stem and spinal cord. A summary of their characteristics follows. peripheral serotonin cannot cross the blood–brain barrier. norepinephrine. glutamate) 2. Serotonin receptors are found in regions of the CNS that are associated with mood and anxiety and are also thought to be involved in temperature regulation.

ADH secretion is controlled by the osmolarity of the extracellular fluid. Producing oxytocin and ADH. vasomotor tone or vasoconstriction is increased. cold. in others. When osmolarity is high. In the endocrine system. They are relayed to the cerebral cortex. pain. evaluates the significance of the impulses. and hormones in the blood. vasomotor tone or vasoconstriction is decreased. less ADH is secreted. Regulating body temperature. it is the center for motor control. another anterior pituitary hormone. vomiting. reasoning. and muscle position sense. if the respiratory center is stimulated. Regulating anterior pituitary hormones. The hypothalamus. other parts send impulses to peripheral structures and are called motor areas. and growth hormone. sweating and dilation of blood vessels in the skin lower the temperature.” which cause the anterior pituitary to secrete these hormones. Around the sensory and motor areas are the “association” areas. 6. water. These sensations produce only a crude awareness at the thalamic level. quality. swallowing. and salivating. and limbic system. memory. medulla oblongata. When nerve impulses from the hypothalamus excite the vasomotor center. sneezing. and other body functions. arterial blood pressure. more ADH is secreted. Together with the midbrain. In the autonomic nervous system. Reticular Activating System The reticular activating system is a network of neurons that extends from the spinal cord through the medulla and pons to the thalamus and hypothalamus. Specific neuroendocrine functions include: 1. and blood pressure is raised. Some parts of the cortex receive incoming nerve impulses and are called sensory areas. For example. where they are interpreted regarding location. electrolytes. It is anatomically connected to the posterior pituitary gland. There is a hypothalamic releasing factor for each hormone. These areas analyze the information received by the sensory areas and decide on the appropriate response. When os5. and it regulates the activity of the anterior pituitary. 3. and voluntary body movements.76 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Cerebral Cortex The cerebral cortex is involved in all conscious processes. In the CNS. and significance. such as learning. Regulating the physical changes associated with emotions (eg. and vasomotor centers. appetite. increased blood pressure and heart rate). Medulla Oblongata The medulla oblongata contains groups of neurons that form the vital cardiac. The hypothalamus secretes “releasing factors. spinal cord. Thalamus The thalamus receives impulses carrying sensations such as heat. molarity is low. The vasomotor center in the medulla oblongata and pons maintains a state of partial contraction in blood vessels (vasomotor tone). which are stored in the posterior pituitary gland and released in response to nerve impulses from the hypothalamus. ADH helps maintain fluid balance by controlling water excretion. respiratory rate and depth are increased. The hypothalamus is stimulated or inhibited by nerve impulses from different portions of the nervous system and by concentrations of nutrients. which occupy the greater portion of the cortex. including thyroid-stimulating hormone. reticular activating system. the temperature is raised. When body temperature is elevated. intensity. body temperature. 4. The thalamus also relays motor impulses from the cortex to the spinal cord. verbalization. Oxytocin initiates uterine contractions to begin labor and delivery and helps to release milk from breast glands during breastfeeding. This means that water is retained in the body to dilute the extracellular fluid and return it toward normal or homeostatic levels. these structures form the brain stem. and more water is excreted in the urine. the hypothalamus controls the secretion of all pituitary hormones. The medulla and pons varolii also contain groups of neurons from which originate cranial nerves 5 through 12. When heat loss is decreased. and satiety centers. it is connected with the thalamus. It receives impulses from all parts of the body. heart rate. ACTH. When body temperature is low. sweating ceases and vasoconstriction occurs. respiratory. and cerebral cortex interact to produce the feelings associated with emotions. hormone levels. In some instances. respiratory rate and depth are decreased. The hypothalamus can exert excitatory or inhibitory effects on the vasomotor center. with the overall effect of relative vasodilation and lowering of arterial blood pressure. . the response may be to store the perception in memory. The medulla also contains reflex centers for coughing. The hypothalamic factor called prolactin-inhibiting factor inhibits secretion of prolactin. If the respiratory center is depressed. gastrointestinal motility. thalamus. Regulating food and water intake by the hypothalamic thirst. Assisting in regulation of arterial blood pressure by its effects on the vasomotor center. Hypothalamus The hypothalamus has extensive neurologic and endocrine functions. 2. It constantly collects information about the internal environment of the body and helps maintain homeostasis by making continuous adjustments in water balance. hunger. When the impulses from the hypothalamus inhibit the vasomotor center. depending on which portions of the hypothalamus are stimulated. it may involve stimulation of motor centers to produce movement or speech.

In the extrapyramidal system. the sleep–wake cycle. sometimes called centrally active drugs. Hypoglycemia (low blood sugar) may cause mental confusion. and impulses from the left control muscle movements of the right side. nerve fibers originate in the cerebral cortex. a neurotransmitter produced in several areas of the brain. although they may have irreversible brain damage. Cerebellum The cerebellum. purposeful movements. Oxygen is carried to the brain by the carotid and vertebral arteries. where the fibers cross. Many nerve impulses from the limbic system are transmitted through the hypothalamus. CNS depressant drugs (eg. depression causes sedation and loss of consciousness. opioid analgesics. It participates in regulation of feeding behavior. which is connected with motor centers in the cerebral cortex and basal ganglia. Limbic System The limbic system borders and interconnects with the thalamus. Normal function is influenced by dopamine. Mild CNS depression is characterized by lack of interest in surroundings and inability to focus on a topic (short attention span). Impulses are then carried from the spinal cord to skeletal muscle. anger. along sensory and motor nerve fibers. Such degeneration in central neurons leads to a form of encephalopathy known as Wernicke-Korsakoff syndrome. there is drowsiness or sleep. Cerebral cortex cells are very sensitive to lack of oxygen (hypoxia). each of which is the point of origin for a pair of spinal nerves. Thiamine deficiency can reduce glucose use by approximately half and can cause degeneration of the myelin sheaths of nerve cells. emotions (eg. Basal Ganglia The basal ganglia are concerned with skeletal muscle tone and orderly activity. and paralysis. and behavior (eg.CHAPTER 5 PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM 77 and decides which impulses to transmit to the cerebral cortex. In the pyramidal or corticospinal tract. antipsychotics. are broadly classified as depressants or stimulants. hypothalamus. Pyramidal and Extrapyramidal Systems The pyramidal and extrapyramidal systems are pathways out of the cerebral cortex. and permanent damage to the cerebral cortex. Pyramidal and extrapyramidal systems intermingle in the spinal cord. crying). glucose. Because the fibers cross in the medulla. It also excites or inhibits motor nerves that control both reflex and voluntary movement. It also helps to maintain balance and posture by receiving nerve impulses from the inner ear that produce appropriate reflex responses. The brain requires more oxygen than any other organ. disease processes affecting higher levels of the CNS involve both tracts. It consists of 31 segments. coordinates muscular activity. and is a center for reflex actions. physiologic changes in blood pressure. respiration. the substantia nigra. sadness). dizziness. which is characterized by rigidity and increased muscle tone. cause dopamine to be released in decreased amounts. Degeneration in peripheral nerves leads to polyneuritis and muscle atrophy. impulses from the right side of the cerebral cortex control skeletal muscle movements of the left side of the body. Stimulation of these neurons produces wakefulness and mental alertness. Brain Metabolism To function correctly. where they end at various levels. and septum. It carries impulses to and from the brain. weakness. The fibers are called extrapyramidal because they do not enter the medullary pyramids and cross over. People in whom hypoxia is relatively prolonged may survive. go down the brain stem to the medulla. hippocampus. and interruption of blood supply causes immediate loss of consciousness. Spinal Cord The spinal cord is continuous with the medulla oblongata and extends down through the vertebral column to the sacral area. Reflexes are involuntary responses to certain nerve impulses received by the spinal cord (eg. pleasure. When several skeletal muscles are involved. fear. Thiamine is required for production and use of glucose. amygdala. Degenerative changes in one of these areas. some are contracted and some are relaxed for smooth. glia and brain stem. As depression progresses. heart rate. fibers originate mainly in the premotor area of the cerebral cortex and travel to the basal gan- DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Drugs affecting the CNS. and continue down the spinal cord. basal ganglia. This process is a factor in the development of Parkinson’s disease. Brain stem cells are less sensitive to hypoxia. Glucose is required as an energy source for brain cell metabolism. thus. laughing. sedative-hypnotics) produce a general depression of the CNS when given in sufficient dosages. aggression. loss of consciousness. convulsions. the knee-jerk and pupillary reflexes). and hormone secretion occur in response to the emotions. The cord is a pathway between the brain and the peripheral nervous system. the brain must have an adequate and continuous supply of oxygen. and thiamine. decreased .

& Hall. B. respiratory failure. 3. Philadelphia: W. Excessive stimulation can cause convulsive seizures.78 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM muscle tone. How would you expect a person with excessive CNS stimulation to look and behave? SELECTED REFERENCES Review and Application Exercises 1. What part of the brain contains vital respiratory and cardiovascular centers? 7. and learning? 6. heat. Saunders. dopamine. norepinephrine. What part of the brain is concerned mainly with thoughts. T.) (2000). and insomnia. 7th ed. excessive talking. D. . & Gourley. Central nervous system stimulants produce a variety of effects. cardiac dysrhythmias. GABA. mental alertness. Increasing stimulation produces hyperactivity. J. C. Where are neurotransmitters synthesized and stored? 2. and death. How would you expect a person with CNS depression to look and behave? 8. (2000). R. Severe CNS depression produces unconsciousness or coma. Philadelphia: Lippincott Williams & Wilkins. and cold. What are the main functions of acetylcholine. A. 10th ed. and death. harmful CNS stimulation by these drugs. What events occur at the synapse between two neurons? Guyton. and decreased fatigue. Once a neurotransmitter is released and acts on receptors. loss of reflexes. Because it is difficult to avoid excessive. reasoning. Mild stimulation is characterized by wakefulness. E. and serotonin? 5. nervousness. (Eds. E. and decreased perception of sensations such as pain. CNS stimulants are less useful for therapeutic purposes than are CNS depressants. how are the remaining molecules inactivated? 4. decreased ability to move. Textbook of medical physiology. Herfindal. Textbook of therapeutics: Drug and disease management.

✔ Constipation is a common adverse effect of opioid analgesics. ask someone for assistance. Tylenol No. . heat and cold applications) instead of or along with analgesics. Do not increase the dose and do not take medication more often than prescribed. and shortens the duration of action. Metamucil daily or a mild laxative every other day may be needed. ask a health care provider. ✔ Take only as prescribed. whether taken alone or in a combination product. and blurred vision. Oxycontin). ask the physician or nurse about potential methods of pain management. Lorcet. Crushing or chewing causes immediate release of the drug. around the clock. The tablets are formulated to release the active drug slowly. some antihistamines. a narcotic may be alternated with a non-narcotic analgesic or a combination product containing a narcotic and nonnarcotic may be effective. If desired effects are not achieved. ✔ Stay in bed at least 30–60 minutes after receiving an opioid analgesic by injection. they are especially important with opioid analgesics because of potentially serious adverse reactions. for chronic pain. such as whole-grain cereals. The maximum recommended daily dose. It is better to take adequate medication and be able to cough. exercise. ✔ For acute episodes of pain. Self-administration ✔ Take oral narcotics with 6–8 oz of water. vomiting. Vicodin. even coma. or operate machinery when drowsy or dizzy or when vision is blurred from medication. and falls when walking around. excessive drowsiness. ask how postoperative pain will be handled. Use of a narcotic analgesic for acute pain is acceptable and unlikely to lead to addiction. cook. drive a car. It may be prevented or managed by eating highfiber foods. These are safety measures to prevent falls or other injuries because these analgesics may cause drowsiness. 8 tablets or capsules containing 500 mg each or 12 tablets containing 325 mg each). MS Contin. ✔ For pain that is not relieved by a non-narcotic analgesic. and because analgesics may mask pain for which medical attention is needed. ✔ When a choice of analgesics is available. including drug dependence. difficulty in breathing. acetaminopen or ibuprofen) may be taken. drowsiness. weakness. ✔ Do not crush or chew long-acting tablets (eg. sleeping pills) while taking opioid analgesics. and vegetables. Do not object to having bedrails up and asking for assistance to ambulate when receiving a strong narcotic analgesic. ✔ For pain that is not relieved by nondrug treatments. If unsure whether a combination product contains acetaminophen. unsteady gait. most opioids may be taken as needed. Lortab. is 4000 milligrams (eg. deep breathe. If it is necessary to get out of bed. use the least amount of the mildest drug that is likely to be effective in a particular situation. over several hours. ✔ When hospitalized. ✔ Do not drink alcohol or take other drugs that cause drowsiness (eg. ✔ Omit one or more doses if severe adverse effects occur (eg. and so on. a nonnarcotic analgesic (eg. when effective. severe nausea. drinking 2–3 quarts of fluid daily. and being as active as tolerated. and ambulate than to avoid or minimize pain medication and be unable to perform activities that promote recovery and healing.CLIENT TEACHING GUIDELINES Opioid (Narcotic) Analgesics General Considerations ✔ Use nonpharmacologic treatments of pain (eg. Injected drugs may cause dizziness. 3) contain acetaminophen and there is a risk of liver failure from high doses of acetaminophen or from lower doses in people who already have liver damage (eg. sedative-type drugs for nervousness or anxiety. alcohol abusers). ✔ Most combination products (eg. how you need to report pain and request pain medication. or constipation) and report to a health care provider. and difficulty in breathing. For example. if anticipating surgery. with a high risk of overdose and adverse effects. For someone unable to take these preventive measures. Percocet. the drugs should be taken on a regular schedule. report to the physician. Combining drugs with similar effects may lead to excessive sedation. ✔ Do not smoke. fruits. with or after food to reduce nausea. Although these principles apply to all medications.

chapter 7 Analgesic–Antipyretic– Anti-inflammatory and Related Drugs Objectives AFTER STUDYING THIS CHAPTER. NSAIDs. Discuss the use of NSAIDs and antigout drugs. 8. they help regulate many cell functions and participate in the inflammatory response. Drugs discussed in this chapter include aspirin (acetylsalicylic acid or ASA). and principles of therapy. 7. analgesic. Compare and contrast aspirin. acetaminophen. Identify factors influencing the use of aspirin. aspirin-related drugs that are often called nonsteroidal anti-inflammatory drugs (NSAIDs. Discuss aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) in terms of mechanism of action. Critical Thinking Scenario You are working in an emergency room when parents bring in their 2-year-old son who has just ingested half a bottle of acetaminophen (Tylenol). and anti-inflammatory doses of aspirin. which act briefly in the area where they are produced and are then inactivated. ibuprofen). The child does not appear acutely ill and the parents become very upset when the physician wants to admit the child. triptans. Reflect on: ᮣ Why is Tylenol overdose potentially so serious for this young child? ᮣ What would emergency and follow-up treatment for Tylenol overdose be? ᮣ How has this child’s developmental stage increased the likelihood for accidental poisoning? ᮣ Develop a teaching plan for this family to prevent recurrence. and inflammation. fever. Aspirin. Prostaglandins exert various and opposing effects in different body tissues (Table 7–1). other NSAIDs. symptoms associated with many injuries and illnesses. Differentiate between traditional NSAIDs and cyclooxygenase-2 inhibitors. Discuss the role of prostaglandins in the etiology of pain. Discuss recognition and management of acetaminophen toxicity. 99 . 6. 2. NSAIDs. and acetaminophen can also be called antiprostaglandin drugs. and ergot antimigraine drugs. nursing process. contraindications to use. eg. Arachidonic acid is then metabolized by cyclooxygenase enzymes to produce prostaglandins. because they inhibit the synthesis of prostaglandins. 9. Prostaglandins are chemical mediators found in most body tissues. 4. 5. and/or inflammation. and drugs used to prevent or treat gout and migraine. 3. His parents have recently come to this country from Mexico and speak very little English. Differentiate among antiplatelet. the prototype. other NSAIDs. Teach clients interventions to prevent or decrease adverse effects of aspirin. They are formed when cellular injury occurs and phospholipids in cell membranes release arachidonic acid. OVERVIEW The analgesic–antipyretic–anti-inflammatory drug group includes chemically and pharmacologically diverse drugs that share the ability to relieve pain. fever. and acetaminophen. Discuss the use of NSAIDs. indications for use. and acetaminophen in terms of indications for use and adverse effects. 10. THE STUDENT WILL BE ABLE TO: 1. and acetaminophen in special populations.

especially platelets. pressure. Common conditions that are characterized by pain. edema results from leakage of blood plasma into the area. and pain. more blood flows through the skin. or persistent. endothelium. and bleeding. bone. inflammation. inflammation may be acute or chronic. and body temperature usually stays within normal range. Fever may be produced by dehydration. Both local and systemic manifestations vary according to the cause and extent of tissue damage. and weakness. As a result. macrophages. When fever occurs. In addition. and regulate blood circulation. fever. it is thought to occur in small amounts or to be in- . and pain occurs when pain receptors on nerve endings are stimulated by heat. heat. vascular smooth muscle cells.100 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM TABLE 7–1 Prostaglandin D2 E2 Prostaglandins Locations Airways. vascular smooth muscle To aid understanding of prostaglandins. PAIN. platelets. some drugs. and for which the drugs discussed in this chapter are used. vasoconstriction and vasodilation) and platelet function. It is an attempt by the body to remove the damaging agent and repair the damaged tissue. the gastrointestinal (GI) tract. the prostaglandins help regulate vascular tone (ie. MECHANISM OF ACTION Aspirin. Fever is an elevation of body temperature above the normal range. they decrease gastric acid secretion. eyes. the heat-regulating center in the hypothalamus is reset so that it tolerates a higher body temperature. or diseases involving the hypothalamus. and inflammation. blood vessels dilate. and the female reproductive system). Prostaglandins sensitize pain receptors and increase the pain associated with other chemical mediators such as bradykinin and histamine (Box 7–1). 7–1). brain injury. their roles in pain. GI tract. endothelial cells. COX-1 is normally synthesized continuously and present in all tissues and cell types. When there is excessive heat production. and the kidneys. brain. edema. Inflammation is the normal body response to tissue damage from any source and it may occur in any tissue or organ. and prostaglandins. Inhibition of COX-1 activity in platelets may be more responsible for GI bleeding than inhibition in gastric mucosa. have been identified. chemicals released by the damaged cells. In the cardiovascular system. or destroys tissue. there is a balance between heat production and heat loss so that a constant body temperature is maintained. It is a common human ailment and may occur with tissue injury and inflammation. called COX-1 and COX-2. platelets Effects • • • • • • • • • • • • • • • Bronchoconstriction Bronchodilation Gastroprotection Increased activity of GI smooth muscle Increased sensitivity to pain Increased body temperature Vasodilation Bronchoconstriction Increased activity of GI smooth muscle Increased uterine contraction (eg. kidneys. are described in Box 7–2. fever. Drug-induced inhibition of these prostaglandins results in the adverse effects associated with aspirin and related drugs. mast cells Brain. menstrual cramps) Decreased platelet aggregation Gastroprotection Vasodilation Increased platelet aggregation Vasoconstriction F2 Airways. AND INFLAMMATION Pain is the sensation of discomfort. loss of appetite. platelets Thromboxane A2 Kidneys. and acetaminophen inactivate cyclooxygenases. kidneys. sweating occurs. increased erythrocyte sedimentation rate. FEVER. Because inflammation may be a component of virtually any illness. kidneys. Aspirin and traditional NSAIDs inhibit both COX-1 and COX-2 enzymes. mechanisms to increase heat loss are activated. Local manifestations are redness. Body temperature is controlled by a regulating center in the hypothalamus. edema. lethargy or malaise. anti-inflammatory drugs are needed when the inflammatory response is inappropriate. headache. Redness and heat result from vasodilation and increased blood supply. infectious processes. along with bacterial toxins and other substances. these prostaglandins help to maintain adequate blood flow and function. Systemic manifestations include leukocytosis. NSAIDs. increase mucus secretion. vascular smooth muscle I2 (Prostacyclin) Brain. prostaglandins act as pyrogens (fever-producing agents). fever. ulceration. Prostaglandins produced by COX-1 are important in numerous homeostatic functions and are associated with protective effects on the stomach and kidneys. However. In the kidneys. Prostaglandin formation is stimulated by such circumstances and. especially gastric irritation. and inflammation are described in the following section. brain. In the stomach. the enzymes required for prostaglandin formation (Fig. COX-2 is also normally present in several tissues (eg. hurt. Normally. abnormal. or distress. Two forms of cyclooxygenase. uterus.

The peak effects of histamine occur within 1 to 2 minutes of its release and may last as long as 10 minutes. pruritus. also called anaphylatoxins. which are abundant in skin and connective tissue. causes vasodilation. Thus. histamine is highly vasoactive. Histamine is formed (from the amino acid histidine) and stored in most body tissue. Histamine is the first chemical mediator released in the inflammatory response and immediate hypersensitivity reactions (anaphylaxis). C5a performs the same functions as C3a and also promotes movement of WBCs into the injured area (chemotaxis). both types of receptors mediate hypotension (in anaphylaxis). More specifically. neutrophils. and headache. basophils. C3a causes or increases smooth muscle contraction. The activated kinins increase and prolong the vasodilation and increased vascular permeability caused by histamine. When histamine binds with these receptors. increases vascular permeability. and platelets. and uterus. and TNF-alpha can induce each other’s release. vasodilation. including fever. and secretion of lysosomal enzymes by leukocytes. especially those in which the antigen is a microbial agent. lymphocytes. thereby inducing formation of leukotrienes and other substances that increase vascular permeability and chemotaxis. and intestinal secretions. tissue injury. In the immune response. skin flushing. stimulating sensory nerve endings to cause pain and itching. white blood cells (WBCs) increase in the area and ingest damaged cells to remove them from the area. is derived from arachidonic acid metabolism and has multiple inflammatory activities. The system is initiated by an antigen–antibody reaction or by tissue injury. release histamine into the vascular system in response to stimuli (eg. act mainly by liberating histamine from mast cells and platelets. It then acts on target tissues through both histamine-1 (H1) and histamine-2 (H2) receptors. Thus. they release enzymes that activate kinins. PAF effects can occur in virtually every organ and tissue. Platelet-activating factor (PAF). They also cause pain by stimulating nerve endings for pain in the area. degranulation of mast cells and basophils. Because these cells are widely distributed. Bradykinin is a kinin in body fluids that becomes physiologically active with tissue injury. vascular permeability. When histamine binds to these receptors. production of nasal mucus. after which it is inactivated by histaminase (produced by eosinophils) or N-methyltransferase. bradykinin may aggravate and prolong the erythema. GI tract. and some drugs). resulting events include contraction of smooth muscle. stimulating salivary. It is produced by mast cells.CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 101 BOX 7–1 CHEMICAL MEDIATORS OF INFLAMMATION AND IMMUNITY cytokines that protect nearby cells from invasion by intracellular microorganisms. on surrounding cells. bronchial. antigen–antibody reaction. including increased vascular permeability and chemotaxis of macrophages. Once released. Cytokines may act on the cells that produce them. They also limit the growth of some cancer cells. It enables the body to produce inflammation and localize an infective agent. the complement system breaks down antigen–antibody complexes. and their effects are therefore similar to those of histamine. platelets) and pathogenic microorganisms (eg. H1 receptors are located mainly on smooth muscle cells in blood vessels and the respiratory and GI tracts. contraction of esophageal muscles. Besides causing platelet aggregation. tachycardia. and basophils. and causes IL-1 and tumor necrosis factor–alpha (TNF-alpha) to be released. Two major types of cytokines are interleukins (produced by leukocytes) and interferons (produced by T lymphocytes or fibroblasts). Interferons are . such as viruses and rickettsiae. complement destroys cell membranes of body cells (eg. viruses). and dilation of capillaries in the skin. monocytes. and stimulating movement of eosinophils into injured tissue. or on distant cells if sufficient amounts reach the bloodstream. More specific reactions include increased vascular permeability. and opsonization (coating a microbe or other antigen so it can be more readily phagocytized). In addition. When tissue cells are damaged. neutrophils. C3a and C5a. with high concentrations in mast cells. Activation yields products with profound inflammatory effects. like prostaglandins and leukotrienes. gastrointestinal (GI) tract. red blood cells. Mast cells. IL-1. and platelets. Interleukin-1 (IL-1) mediates several inflammatory responses. H2 receptors are also located in the airways. causing vasodilation (increasing blood flow to the area and producing hypotension) and increasing permeability of capillaries and venules (producing edema). and other tissues. and pain of local inflammatory reactions. stimulation of sensory nerves. PAF. it diffuses rapidly into other tissues. Other effects include contracting smooth muscles in the bronchi (producing bronchoconstriction and respiratory distress). When histamine is released from mast cells and basophils. cytokines act locally and systemically to produce inflammatory and immune responses. it activates the lipoxygenase pathway of arachidonic acid metabolism in neutrophils and macrophages. increased mucus secretion and bronchodilation in the airways. there is increased secretion of gastric acid by parietal cells in the stomach mucosal lining. PAF activates neutrophils. Components of the system (called C1 through C9) are activated in a cascade type of reaction in which each component becomes a proteolytic enzyme that splits the next component in the series. attracts eosinophils. heat. chemotaxis. and IL-2 (also called T-cell growth factor) is required for the growth and function of T lymphocytes. and degranulation of basophils (with additional release of histamine and other mediators) in the bloodstream. gastric. It also increases mucous gland secretion. bacteria. increased vascular permeability. Complement is a group of plasma proteins essential to normal inflammatory and immunologic processes. In allergic reactions. When the WBCs die. inhibition of lymphocyte function.

nausea. including alcohol (especially red wine). To relieve fever. interfere with blood coagulation. and physical and emotional stress. Aspirin and traditional NSAIDs also have antiplatelet effects that differ in mechanism and extent. urate deposits produce periodic episodes of severe pain. and less efficient in repairing itself. Overall. the drugs act on the hypothalamus to decrease its response to pyrogens and reset the “thermostat” at a lower level. however. painful. the fluid reduces friction between tendons and bones or ligaments). aspirin has greater effects. In the GI tract. Rheumatoid arthritis (RA)—a chronic. The COX-2 inhibitor drugs are NSAIDs designed to selectively inhibit COX-2 and relieve pain and inflammation with fewer adverse effects. edema. gout). Common forms include acute painful shoulder. irregular patterns of eating and sleeping. the drugs prevent prostaglandins from increasing the pain and edema produced by other substances released by damaged cells. decreased range of motion.” “housemaid’s knee. and inflammation (gouty arthritis). COX-2 is also induced by trauma and Helicobacter pylori infection. A small single dose (325 mg) irreversibly acetylates circulating platelets within a few minutes. and disruptive of usual activities of daily living. OTHER NSAIDs. oral contraceptives). athletic injuries such as sprains). Most other NSAIDs bind reversibly with platelet COX-1 so that antiplatelet effects occur only while the drug is present in the blood. It is considered an autoimmune disorder in which the body attacks its own tissues.102 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM BOX 7–2 SELECTED CONDITIONS FOR WHICH ASPIRIN. release of inflammatory mediators. antihypertensives. a waste product of protein metabolism. INDICATIONS FOR USE These drugs are widely used to prevent and treat mild to moderate pain and/or inflammation associated with musculoskeletal disorders (eg. COX-2 is induced by inflammatory chemical mediators such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). The resulting hyperuricemia may be asymptomatic or may lead to urate deposits in various tissues. active until stimulated by pain and inflammation. Inhibition of COX-2 results in the therapeutic effects of analgesia and anti-inflammatory activity. and effects last for the lifespan of the platelets (7 to 10 days). and deformity occur as the disease advances. dental extraction. aspirin and other NSAIDs differ in their approved uses. AND ACETAMINOPHEN ARE COMMONLY USED Bursitis—inflammation of a bursa (a cavity in connective tissue that contains synovial fluid.” and bunions. Onset may occur before 16 years of age. For inflammation. chocolate. usually aggravated by movement. some medications (eg. and friction and abrasion lead to inflammation of the synovial membrane lining of the joint. Juvenile rheumatoid arthritis is a chronic. and irritation of nerve endings. but one theory is that certain circumstances cause an imbalance of chemicals (eg. and increase the risk of bleeding. some foods (eg. Migraine—a type of headache characterized by periodic attacks of pain. To relieve pain. urate deposits may form renal calculi or cause other damage. aspirin acts both centrally and peripherally to block the transmission of pain impulses. Migraine occurs more often in women than men and may be associated with menses. there is less padding and lubricating fluid. then binds irreversibly to platelet COX-1. edema. and other acute and chronic conditions. inflammatory. throbbing or pulsating in nature. Knee OA. inflammatory disorder that affects hingelike joints. a prostaglandin derivative. In the kidneys. joint stiffness. tissues around these joints. but all the drugs except acetaminophen and the COX-2 inhibitors inhibit platelet aggregation. dysmenorrhea. This imbalance results in vasodilation. its usage has declined for most indications. and eventually other body organs (systemic effects). largely because of adverse effects on the gastrointestinal . Related drugs act peripherally to prevent sensitization of pain receptors to various chemical substances released by damaged cells. minor surgery (eg. more susceptible to injury. and increased sensitivity to light and sound. Dysmenorrhea—pain associated with menstruation. underlying bone is exposed. and thereby inhibits platelet aggregation. The pain is often worse on one side of the head. prostaglandins produced by COX-2 are associated with pain and other signs of inflammation. serotonin. they do not cure the underlying disorders that cause the symptoms. Although aspirin is effective in many disorders. often develops from repeated joint injury or repetitive motion. “tennis elbow. headache. The etiology is unknown. minor trauma (eg. especially stomach damage. When aspirin is ab- sorbed into the bloodstream. tendinitis. the acetyl portion dissociates. In the musculoskeletal system. Gout—a disorder characterized by an inability to metabolize uric acid. episiotomy). a common type. This action prevents synthesis of thromboxane A2. osteoarthritis. Pain in and around the knee occurs early in the disease process. prostaglandins) in the brain. As joint cartilage deteriorates over time. Thus. systemic disease that may cause joint or connective tissue damage and visceral lesions throughout the body. The joint becomes unstable. thought to be caused by prostaglandins that increase contractility of the uterine muscle. Despite many similarities. Numerous circumstances have been implicated as “triggers” for the chemical imbalance and migraine. Osteoarthritis (OA)—a disease that affects the cartilage of weight-bearing joints and produces pain. In inflamed tissues. often in the feet. and progressive loss of mobility. Although these drugs relieve symptoms and contribute greatly to the client’s comfort and quality of life. aged cheeses). a common cause of peptic ulcer disease. moderate or severe in intensity.

Prostaglandins play important roles in normal body functions as well as inflammatory processes. lowdose aspirin is increasingly prescribed for clients at risk of myocardial infarction or stroke from thrombosis. or hormonal stimuli Arachidonic acid Traditional NSAIDs block COX-1 and COX-2 enzymes COX-2 inhibitor NSAIDs block COX-2 enzyme Cyclooxygenase-1 (COX-1) Cyclooxygenase-2 (COX-2) Physiologic prostaglandins Figure 7–1 Physiologic and pathologic (ie. Some NSAIDs such as ibuprofen (Motrin) and related drugs are widely used as anti-inflammatory agents and analgesics. nonaspirin NSAIDs also are contraindicated because hypersensitivity reactions may occur with any drugs that inhibit prostaglandin synthesis.CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 103 Cell activated by physical. maintain blood flow to mucosa) Renal protection (help maintain blood flow and function) Regulate smooth muscle tone in blood vessels (eg. history of hypersensitivity reactions. inflammatory) prostaglandins: Actions of antiprostaglandin drugs. 65). irritation. which can be given orally and parenterally. In addition. an allergic reaction to other NSAIDs. asthma. Most of the other NSAIDs are too toxic to use as analgesics and antipyretics. aspirin is contraindicated in the presence of viral infections such as influenza or chickenpox because of its association with Reye’s syndrome. and impaired renal function. Celecoxib (Celebrex) is also used to treat familial adenomatous polyposis. Several NSAIDs are formulated as eye drops for use in treating eye disorders (see Chap. bronchodilation) Regulate blood clotting Pathologic prostaglandins Inflammation Vasodilation ↑ Capillary permeability Edema Pain Leukocytosis Activate white blood cells to release inflammatory cytokines tract and the advent of newer drugs. chemical. ulceration. in which the drug reduces the number of polyps and may decrease risks of colon cancer. bleeding) as well as anti-inflammatory effects. They are used primarily in rheumatoid arthritis and other musculoskeletal disorders that do not respond to safer drugs. but it lacks anti-inflammatory and antiplatelet effects. gastrointestinal (GI) or other bleeding disorders. This indication stems from its antiplatelet activity and resultant effects on blood coagulation (ie. Selective COX-2 inhibitors are contraindicated for clients with a history of peptic ulcers. GI bleeding. which differs chemically from aspirin and other NSAIDs. ketorolac (Toradol). In people who are allergic to aspirin. Acetaminophen. ↑ mucus production. In children and adolescents. At the same time. CONTRAINDICATIONS TO USE Contraindications to aspirin and nonselective NSAIDs include peptic ulcer disease. is commonly used as an aspirin substitute for pain and fever. Inhibition of both COX-1 and COX-2 by traditional NSAIDs produces adverse effects on the stomach (eg. vasodilation) and lungs (eg. Selective inhibition of COX-2 produces anti-inflammatory effects while maintaining protective effects on the stomach. or severe renal impairment. celecoxib and valdecoxib are contraindicated in clients . is used only as an analgesic. GI protection (↓ gastric acid. decreased clot formation).

It undergoes oxidation and conjugation in the liver and its metabolites are excreted through the kidneys. capsules. In alkaline urine (eg. It can be purchased in plain. It is metabolized in the liver and excreted through the kidneys. NSAIDs Propionic acid derivatives include fenoprofen (Nalfon). joints. ketoprofen. and effervescent tablets and rectal suppositories. When it fails to close. colds. Potentially serious adverse effects include GI ulceration. (The ductus arteriosus joins the pulmonary artery to the aorta in the fetal circulation. hemolytic anemia. a commonly used drug. and fever. is well absorbed with oral administration. an active metabolite. In plasma. peaks in 1 to 2 hours. It is effective in pain of low to moderate intensity. Aspirin is distributed to all body tissues and fluids. It is not marketed in liquid form because it is unstable in solution. Ketorolac is used only for pain. and osteoarthritis. liver. and dosage ranges of individual drugs are listed in Drugs at a Glance: Analgesic. causing severe cardiopulmonary problems. and naproxen are available OTC. renal excretion of salicylate is greatly increased. Ibuprofen. people tend to underestimate its usefulness. However. and lasts 4 to 6 hours. intravenous (IV) indomethacin is approved for treatment of patent ductus arteriosus in premature infants. Although these drugs are usually better tolerated than aspirin.) Other drugs related to this group are etodolac (Lodine). It is available by prescription and OTC. Hematomas and wound bleeding have been reported with postoperative use. mental confusion. Etodolac reportedly causes less gastric irritation. Taking aspirin with food slows absorption. Because it is a nonprescription drug and is widely available. indications for use. rheumatoid arthritis. These effects are especially associated with indomethacin. Parenteral ketorolac reportedly compares with morphine and other opioids in analgesic effectiveness for moderate or severe pain. especially in older adults at high risk for GI bleeding. In addition to their use as anti-inflammatory agents. pH of 8). peaks in 1 to 2 hours. and although it can be given orally. Aspirin has a short half-life of 15– 20 minutes because it is rapidly converted to salicylic acid. and tolmetin (Tolectin). and the central nervous system (CNS). depression. its use is limited to 5 days because it increases the risk of bleeding. Aspirin is a home remedy for headaches. breast milk. In addition to other uses. naproxen (Naprosyn). some are used as analgesics and antipyretics. ketorolac should not be administered during labor and delivery. Although adverse reactions occur less often with sulindac and tolmetin. it has less antipyretic effect. trade names. The highest concentrations are found in the plasma. Ibuprofen. These drugs have strong anti-inflammatory effects and more severe adverse effects than the propionic acid derivatives. Its action starts in about 30 minutes. its unique characteristic is that it can be given by injection.104 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM who are allergic to sulfonamides and ketorolac is contraindicated in clients at risk of excessive bleeding. with recommended doses smaller and durations of use shorter than those for prescription formulations. or to clients who are currently taking aspirin or other NSAIDs. causes less gastric irritation. Aspirin is the prototype of the analgesic–antipyretic– anti-inflammatory drugs and the most commonly used salicylate. but also decreases gastric irritation. Diflunisal (Dolobid) is a salicylic acid derivative that differs chemically from aspirin. The drug is highly bound (about 99%) to plasma proteins and has a half-life of about 2 hours. before or during any major surgery. Meloxicam has a serum half-life of 15 to 20 hours (text continues on page 108) SUBGROUPS AND INDIVIDUAL DRUGS Sub-groups and selected individual drugs are described below. and lasts 4 to 6 hours. chewable. ibuprofen (Motrin. chewable tablets. with suspected or confirmed cerebrovascular bleeding. they are much more expensive and may cause all the adverse effects associated with aspirin and other prostaglandin inhibitors. sulindac (Clinoril). It is reportedly equal or superior to aspirin in mild to moderate pain. Compared with aspirin. Salicylic acid has a half-life of 2 to 3 hours at low doses and 6 to 12 hours at therapeutic antiinflammatory doses. flurbiprofen (Ansaid). enteric-coated. influenza and other respiratory infections. in tablets. but many people prefer drugs that cause less gastric irritation. and oxaprozin (Daypro). . Regular aspirin tablets are well absorbed after oral administration. especially that involving the skin. such as arthritis. ketoprofen (Orudis). aspirin binds to albumin (75 to 90%). and nabumetone (Relafen). Anti-inflammatory Drugs. It is useful in inflammatory disorders. heart. for use by adults and children. Oxicam drugs include meloxicam (Mobic) and piroxicam (Feldene). and lungs. including fetal tissues. blood is shunted from the aorta to the pulmonary artery. and oral drops. bone marrow depression. ketoprofen. and psychosis. Absorption of enteric-coated aspirin and rectal suppositories is slower and less complete. Over-the-counter (OTC) products containing these drugs are contraindicated for chronic alcohol abusers because of possible liver damage (with acetaminophen) or stomach bleeding (with aspirin. Thus. or naproxen). This warning states that people who drink three or more alcoholic drinks daily should ask their doctors before taking the products. and has a longer duration of action. Acetic acid derivatives include indomethacin (Indocin). the other drugs were developed in an effort to find equally effective but less toxic derivatives of indomethacin. ketorolac (Toradol). Advil). they are still common. their action starts within 15 to 30 minutes. muscles. muscular aches. and other connective tissue. oral suspension. Antipyretic. ibuprofen. The Food and Drug Administration (FDA) requires an alcohol warning on the labels of all OTC pain relievers and fever reducers.

maximum of 6 in 24 h Aspirin Pain. 40 mg. 11 y. 50 mg two or three times or 75 mg twice or 100 mg once daily) RA: PO 150–200 mg/d in two. 400 mg. others) Indications for Use Pain Fever Adults PO 325–650 mg q4–6h. and stroke: PO 81–325 mg/d Acute rheumatic fever: PO 5–8 g/d. 6–8 y. 325 mg q4–6h. 1–2 y. 480 mg. Rectal suppository 650 mg q4–6h. Anti-inflammatory Drugs Routes and Dosage Ranges Generic/Trade Name Acetaminophen (Tylenol. fever: PO 10–15 mg/kg q4h. Maximum recommended dose for adults is 4 g/d. Recommended doses for weight: 24–35 lb (10. It may be used for all indications.2 kg). 48–59 lb (21.3 kg or above). 160 mg.9 kg). Celecoxib (Celebrex) Osteoarthritis Rheumatoid arthritis Familial adenomatous polyposis (FAP) Diclofenac potassium (Cataflam) Diclofenac sodium (Voltaren. 240 mg. immediate-release tablets.4 kg). Rectal suppository: age under 3 y. then 75 mg/kg/d for 4–6 wk Dosage not established Comments Warning: Overdoses may cause fatal liver damage. up to 60–80 mg/kg/d. 120 mg q4–6h.6 g in 24 h Pain. 486 mg. consult physician. 720 mg in 24 h. age 6–12 y. 162 mg. three or four divided doses 200-mg doses should be taken with food Dosage not established Diclofenac potassium is available only in 50-mg. 650 mg OA. 36–47 lb (16–21. 405 mg. age 3–6 y. 4–11 mo. 2–3 y. Doses may be given q4–6h to a maximum of 5 doses in 24 h. RA: PO 2–6 g/d in divided doses Prophylaxis of MI. 648 mg Juvenile RA: PO 60–110 mg/kg/d in divided doses q6–8h Acute rheumatic fever. from all sources. 72–95 lb (32. 96 lb or above (43.6–15. 80 mg. fever: PO 325– 650 mg q4h PRN. Voltaren XR) Osteoarthritis Rheumatoid arthritis OA: PO 100 mg twice daily or 200 mg once daily RA: PO 100–200 mg twice daily FAP: PO 200 mg twice daily OA: PO 100–150 mg/d in divided doses (eg.4– 43. in divided doses TIAs. 60–71 lb (26. Antipyretic. toxicity occurs at levels above 300 mcg/mL. 324 mg. 4–5 y. (continued ) .CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 105 Drugs at a Glance: Analgesic. maximum 2. or 1000 mg three or four times per day. in divided doses. for 2 wk.5– 26.9– 32. PO 1300 mg/d in divided doses (650 mg twice a day or 325 mg four times a day) Therapeutic serum level of salicylate is 100–300 mcg/mL for treatment of arthritis and rheumatic fever. fever Osteoarthritis (OA). transient ischemic attacks (TIAs) and stroke in men Rheumatic fever Pain.8 kg). 120 mg. Parents and caregivers should ask pediatricians about the amounts of acetaminophen children may take safely. usual single dose. 243 mg. 320 mg. PO 100 mg/kg/d. 9–10 y. maximum 4 g/d Children PO 10 mg/kg or according to age as follows: 0–3 mo.3 kg). TIA. rheumatoid arthritis (RA) Prophylaxis of myocardial infarction (MI). maximum.

increased to a maximum of 1500 mg/d if necessary Pain: PO 500–1000 mg initially. The immediate-release forms should be used to treat acute pain. initial temperature above 39. chewable tablets. RA: PO 300–600 mg three or four times per day Pain: PO 200 mg q4–6h PRN Maximum. 2400 mg/d Pain. for infants) The sustained-release form is not recommended for acute gouty arthritis. PO 20–40 mg/kg/d. . rectal suppository.2°C (102. PediaCare) Indomethacin (Indocin. Lodine XL) Osteoarthritis Rheumatoid arthritis Pain Dosage not established Available in immediaterelease and extendedrelease (XL) tablets of various strengths. 3200 mg/d OA. in two divided doses. dysmenorrhea Adults AS: PO 100–125 mg/d in four or five divided doses (eg. 3200 mg/d Not recommended for use in children <12 years of age Children Comments Diclofenac sodium is available in 25-. initial temperature 39. dysmenorrhea Fever Dosage not established Ibuprofen (Advil. then 250– 500 mg q8–12h OA. dysmenorrhea: PO 400 mg q4–6h PRN Maximum.5°F). It is not recommended for acute pain or dysmenorrhea. dysmenorrhea: (diclofenac potassium only) PO 50 mg three times daily OA.3 mg/kg q12h for a total of three doses Available in numerous dosage forms and concentrations.2°C (102. three.5°F) or less. RA: PO 300–600 mg 3 or 4 times per day. Diflunisal (Dolobid) Osteoarthritis Rheumatoid arthritis Pain Etodolac (Lodine. Antipyretic. 20 mg/kg/d for <60 kg OA. Fenoprofen (Nalfon) Osteoarthritis Rheumatoid arthritis Pain Dosage not established Flurbiprofen (Ansaid) Osteoarthritis Rheumatoid arthritis Osteoarthritis Rheumatoid arthritis Pain. Indocin SR) Osteoarthritis Rheumatoid arthritis Ankylosing spondylitis Tendinitis Bursitis Acute painful shoulder Acute gout Closure of patent ductus arteriosus (IV only) PO. maximum. 25 mg four or five times daily) Pain. RA: PO 500– 1000 mg/d. if necessary 1–12 y: Fever. PO 10 mg/kg q6–8h. RA: PO 200–300 mg/d in two. PO 5 mg/kg q6–8h. or four divided doses OA. increased by 25 mg/d at weekly intervals to a maximum of 150–200 mg/d.106 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Drugs at a Glance: Analgesic. IV 0.2–0. in three or four divided doses Premature infants with patent ductus arteriosus. Anti-inflammatory Drugs (continued ) Routes and Dosage Ranges Generic/Trade Name Indications for Use Ankylosing spondylitis (AS) Pain. oral suspensions (of 100 mg/5 mL). and oral drops (of 40 mg/mL. RA: PO 600– 1200 mg/d in two to four divided doses Pain: PO 200–400 mg q6–8h Maximum according to weight: 1200 mg/d for 60 kg (132 lbs) or more. Motrin. and 75-mg delayedrelease tablets and a 100-mg extendedrelease (XR) tablet. 75 mg/d initially. 50-. 40 mg/kg/d Juvenile arthritis. capsules. including regular tablets. maximum dose.

acute tendinitis. then discontinued Pain.CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 107 Drugs at a Glance: Analgesic. Anaprox. acute painful shoulder. increased to 15 mg once daily if necessary PO 1000–2000 mg/day in one or two doses Naproxen: PO 250– 500 mg twice daily Gout: PO 750 mg initially. dysmenorrhea. 39 kg (84 lb). 100–150 mg/d for clients with impaired renal function IV. then 250 mg q8h until symptoms subside Maximum. those with renal impairment. 5 mL. Antipyretic. IM 30 mg q6h PRN to a maximum of 120 mg/d PO 10 mg q4–6h to a maximum of 40 mg/d Older adults (>65 y). in a suspension. 25 kg (55 lb). then 275 mg q8h until symptoms subside Controlled-release (Naprelan). Note that the names do not contain any letters (eg. Naprelan) Osteoarthritis Rheumatoid arthritis Osteoarthritis Rheumatoid arthritis Juvenile arthritis Ankylosing spondylitis Pain Dysmenorrhea Bursitis Tendinitis Acute gout Dosage not established Juvenile arthritis (naproxen only): PO 10 mg/kg/d in two divided doses. 3–5 d for gout. Ketorolac (Toradol) Moderately severe. 2. dysmenorrhea: PO 25–50 mg q6–8h PRN OA. 1250 mg/d Naproxen sodium: Pain. Oruvail) Pain Dysmenorrhea Osteoarthritis Rheumatoid arthritis Do not give to children <16 years unless directed by a physician. 200 mg once daily Maximum. PO 75–150 mg/d in three or four divided doses until pain and inflammation are controlled (eg. and in immediateand delayed-release formulations Nabumetone (Relafen) Naproxen (Naprosyn) Naproxen sodium (Aleve. RA: PO 150–300 mg/d in three or four divided doses Sustained-release (Oruvail SR). 300 mg/d for regular formulation.5 mL. acute pain. Oral suspension (125 mg/ 5 mL) twice daily according to weight: 13 kg (29 lb). 200 mg/d for extended release. those with weight < 50 kg (110 lbs). SR. 750– 1000 mg once daily Children Comments Ketoprofen (Orudis. IM 15 mg q6h to a maximum of 60 mg/d PO 7. Extended-release capsules are available as generic ketoprofen and Oruvail. 7–14 d for painful shoulder). Meloxicam (Mobic) Osteoarthritis Dosage not established May be taken without regard to meals Available in 500-mg and 750-mg tablets Available in several dosage strength tablets. 7. XL) that indicate long-acting dosage forms.5 mL OTC preparation not recommended for children < 12 y (continued ) . Anti-inflammatory Drugs (continued ) Routes and Dosage Ranges Generic/Trade Name Indications for Use Adults Acute gouty arthritis. for short term (up to 5 days) treatment Dosage not established Treatment is started with one or more injected doses.5 once daily. 5 days. AS: PO 275– 550 mg twice a day Acute gout: PO 825 mg initially. bursitis: PO 550 mg q12h or 275 mg q6–8h Maximum. Maximum duration of both injected and oral doses. 1375 mg/d OA. followed by oral doses when the client is able to take them. IV. RA.

the drugs do not raise blood pressure in normotensive clients) and some clients receiving a COX-2 inhibitor had a small increase in the incidence of myocardial infarction and stroke due to thrombosis. there have been a few cases reported in which hypertension was acutely worsened by the drugs (blood pressure returned to previous levels when the drugs were discontinued. increased to 1800 mg/d if necessary OA. The long half-lives allow the drugs to be given once daily. It is 87% protein bound and has a half-life of 17 hours. It is highly protein bound (97%) and its serum half-life is about 11 hours. Peak action occurs in about 2 hours and effects last 12 to 15 hours. then reduce dosage or discontinue PO 400 mg three times daily initially. Antipyretic. Celecoxib (Celebrex) is well absorbed with oral administration. The formulation of diclofenac potassium (Cataflam) is immediate-release. It is metabolized by the cytochrome P450 enzymes in the liver to inactive metabolites that are then excreted in the urine. RA: PO 10 mg once daily Dysmenorrhea: PO 20 mg twice daily as needed Dosage not established Juvenile RA: PO 20 mg/kg/d in three or four divided doses Dosage not established and is excreted about equally through urine and feces.5 mg/5 mL or 25 mg/5 mL May be taken with or without food Sulindac (Clinoril) Osteoarthritis Rheumatoid arthritis Ankylosing spondylitis Bursitis Tendinitis Acute painful shoulder Acute gout Tolmetin (Tolectin) Valdecoxib (Bextra) Osteoarthritis Rheumatoid arthritis Juvenile rheumatoid arthritis Osteoarthritis Rheumatoid arthritis Dysmenorrhea PO 150–200 mg twice a day.5. acute painful shoulder: PO 200 mg twice a day until pain and inflammation subside (eg. 25 and 50 mg and a suspension containing 12. Piroxicam has a half-life of about 50 hours. Despite the rel- ative safety of these drugs. Thus. Cyclooxygenase-2 inhibitors block production of prostaglandins associated with pain and inflammation without blocking those associated with protective effects on gastric mucosa. and also lasts 12 to 15 hours. Valdecoxib (Bextra) is a newer COX-2 inhibitor. These concerns are being investigated. In addition. action starts quickly. Rofecoxib (Vioxx) acts within 45 minutes and peaks in 2 to 3 hours. It is metabolized in the liver and excreted in urine and feces. maximum.108 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Drugs at a Glance: Analgesic. whichever is lower. . As a result. peaks in about 20 minutes to 2 hours. Diclofenac sodium (Voltaren) is chemically different from but pharmacologically similar to other NSAIDs. A small amount is excreted unchanged in the urine. Formulations are delayed or extended-release and onset of action is therefore delayed. 7–14 d). 1800 mg/d or 26 mg/kg/d. they produce less gastric irritation than aspirin and other NSAIDs. in divided doses PO 20 mg/d or 10 mg twice daily OA: PO 12. Diclofenac has a serum halflife of about 2 hours and is excreted mainly in the urine. 400 mg/d Acute gout. compared with clients receiving a nonselective NSAID (naproxen) or placebo.5–25 mg once daily Acute pain. they are not associated with increased risks of bleeding because they do not have the antiplatelet effects of aspirin and other NSAIDs. others are being developed. but optimal efficacy may not occur for 1 to 2 weeks. dysmenorrhea: PO 50 mg once daily as needed Children Dosage not established Comments Lower doses recommended for patients with low body weight or milder disease Piroxicam (Feldene) Rofecoxib (Vioxx) Osteoarthritis Rheumatoid arthritis Osteoarthritis Pain Dysmenorrhea Dosage not established Dosage not established Available in tablets of 12. the potassium salt may be given for rapid relief of pain and primary dysmenorrhea. Anti-inflammatory Drugs (continued ) Routes and Dosage Ranges Generic/Trade Name Oxaprozin (Daypro) Indications for Use Osteoarthritis Rheumatoid arthritis Adults PO 600–1200 mg once daily Maximum. peak plasma levels and peak action occur approximately 3 hours after an oral dose.

3-d interval between courses of therapy IV 1–2 mg initially. hydrocodone. and it does not interfere with blood clotting. PO 0. PO 400–600 mg/d Hyperuricemia in clients with renal insufficiency. PO 100–200 mg/d Secondary hyperuricemia from anticancer drugs. Acetaminophen is metabolized in the liver.CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 109 Acetaminophen (also called APAP. and soft tissues) and impaired renal function. and zolmitriptan (Zomig). PO 200– 400 mg/d Severe gout. (Probenecid also is used with penicillin. rizatriptan (Maxalt). naratriptan (Amerge). PO 40 mg/kg/d in divided doses Dosage not established Drugs Used in Gout and Hyperuricemia Individual drugs are described below. The probable mechanism for increased risk of hepatotoxicity in this population is that ethanol induces drug-metabolizing enzymes in the liver. concomitant administration of colchicine prevents this effect. sumatriptan (Imitrex). but it lacks anti-inflammatory activity. the supply of glutathione may become depleted. maximum total dose 4 mg Prophylaxis. This uricosuric action is used therapeutically to treat hyperuricemia and gout. Duration of action is 3 to 4 hours. Uric acid is formed by purine metabolism and an enzyme called xanthine oxidase. Colchicine is usually given during initial sulfinpyrazone therapy to prevent acute gout. then 500 mg twice a day PO 100–200 mg twice a day. Approximately 4% is metabolized to a toxic metabolite. called “triptans. In people who abuse alcohol. Probenecid may precipitate acute gout until serum uric acid levels are within the normal range. Acute attacks of gout may result when urate deposits are mobilized. kidneys. however. It is not effective in acute gout but prevents or decreases tissue changes of chronic gout.5 mg q3–6h until response is obtained. liquid. Acetaminophen is well absorbed with oral administration and peak plasma concentrations are reached within 30 to 120 minutes. it is the drug of choice for relieving joint pain and edema. These may be prevented by concomitant administration of colchicine until serum uric acid levels are lowered. vomiting. vomiting. Drugs at a Glance: Drugs for Gout Routes and Dosage Ranges Generic/ Trade Name Allopurinol (Zyloprim) Adults Mild gout. Allopurinol (Zyloprim) is used to prevent or treat hyperuricemia. It is especially useful in chronic gout characterized by tophi (deposits of uric acid crystals in the joints. It is not effective in acute attacks of gouty arthritis but prevents hyperuricemia and tophi associated with chronic gout. which is normally inactivated by conjugation with glutathione and excreted in urine. gradually increased over 1 wk to a maximum of 400–800 mg/d Children Secondary hyperuricemia from anticancer drugs: <6 y. dosages are listed in Drugs at a Glance: Drugs for Gout. Acetaminophen is available in tablet. It has no analgesic or antipyretic effects. or oxycodone for added analgesic effects. a sufficient amount of glutathione is available in the liver to detoxify acetaminophen. The drug promotes resorption of urate deposits and prevents their further development. In acute attacks. most often in treating sexually transmitted diseases. diarrhea) occurs. It is equal to aspirin in analgesic and antipyretic effects. In the absence of glutathione. Colchicine is an anti-inflammatory drug used to prevent or treat acute attacks of gout. Drugs for Migraine Individual drugs are described below. then 0.5–1 mg/d PO 250 mg twice a day for 1 wk.) Sulfinpyrazone (Anturane) is a uricosuric agent similar to probenecid. 6–10 y. frovatriptan (Frova). and rectal suppository forms and is in numerous combination products marketed as analgesics and cold remedies. maximum 800 mg/d Acute attacks. Probenecid (Benemid) increases the urinary excretion of uric acid. Almotriptan (Axert). or GI bleeding.” were developed . the toxic metabolite combines with liver cells and causes damage or fatal liver necrosis. It is often prescribed with codeine. which occurs with gout and with antineoplastic drug therapy. PO 0. In acute or chronic overdose situations. It increases blood levels and prolongs the action of penicillin by decreasing the rate of urinary excretion.5 mg q1h until pain is relieved or toxicity (nausea. Colchicine decreases inflammation by decreasing the movement of leukocytes into body tissues containing urate crystals. PO 150 mg/d. PO 300 mg/d Colchicine Dosage not established Probenecid (Benemid) Sulfinpyrazone (Anturane) >2 y. dosages are listed in Drugs at a Glance: Drugs for Migraine. usual therapeutic doses may cause or increase liver damage. The resulting rapid metabolism of acetaminophen produces enough toxic metabolite to exceed the available glutathione. an abbreviation for N-Acetyl-P-Aminophenol) is a nonprescription drug commonly used as an aspirin substitute because it does not cause nausea. PO 100–200 mg/d. Allopurinol prevents formation of uric acid by inhibiting xanthine oxidase. With usual therapeutic doses. approximately 94% is excreted in the urine as inactive glucuronate and sulfate conjugates.

Proponents of CS cite clinical trials that indicate beneficial effects. Maximum dose. Chondroitin sulfate (CS). if necessary. Maximum dose. CS was first used as a dietary supplement because studies suggested that it would promote healing of cartilage damaged by inflammation or injury. repeat in 5 min. if necessary. Most clients get relief within 1 to 2 hours with all of the oral drugs. Because of their vasoconstrictive properties. The authors concluded that the NSAID relieved pain faster but the effects of CS lasted longer. Maximum. For example. repeat in 4 h if necessary. Maximum. repeat after 2 h if necessary. 5 mg/d Rizatriptan (Maxalt) PO 5–10 mg as a single dose. Caffeine reportedly increases the absorption and vasoconstrictive effects of ergotamine. nausea.5–1 tablet initially.25–2. myocardial infarction. Proponents also tout the safety of CS in comparison with the adverse effects of NSAIDs. may be repeated hourly.5 mg as a single dose. 800 mg CS. Ergotamine is contraindicated during pregnancy and in the presence of severe hypertension. Do not exceed 6 mg/wk. CS is usually taken with food. marigold. ergotamine is erratically absorbed. and therapeutic effects may be delayed for 20 to 30 minutes. They relieve migraine by constricting blood vessels. renal or hepatic disease. 1–2 mg at onset of migraine. there is a theoretical risk of bleeding because of the specifically for the treatment of moderate or severe migraines. one study cited by Fetrow and Avila compared CS with diclofenac sodium.5–1 suppository at onset of migraine. The main adverse effects are reportedly minor stomach upset. 30 mg/d Sumatriptan (Imitrex) PO 25–100 mg as a single dose. 1600 mg CS.25 mg. to stimulate synthesis of new cartilage (by stimulating chondrocytes to produce collagen and proteoglycan). 40 mg/d Zolmitriptan (Zomig) PO 1. peppermint. paresthesias. if necessary. and chondrocytes that produce new collagen and proteoglycans. there is some evidence of effectiveness with few adverse effects. Maximum dose. over 200 lbs. these are described below. pain. may repeat after 2 h if necessary.110 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Drugs at a Glance: Drugs for Migraine Generic/Trade Name Routes and Dosage Ranges Serotonin agonists (Triptans) Almotriptan (Axert) PO 6. up to two suppositories per attack or five suppositories/wk Children: PO 0. They are called selective serotonin 5-HT1 receptor agonists because they act on a specific subtype of serotonin receptor to increase serotonin (5-hydroxytryptamine or 5-HT) in the brain. if necessary. The drugs are metabolized in the liver by monoamine oxidase or cytochrome P450 enzymes. 10 mg/d Ergot Preparations Ergotamine tartrate (Ergomar) Ergotamine tartrate and caffeine (Cafergot) Dihydroergotamine mesylate (DHE 45) PO. comfrey. dizziness. a proteolytic enzyme found in synovial membranes). then 2 mg q30 min. up to 3 months after treatment. is thought to delay the breakdown of joint cartilage (by inhibiting elastase. When given orally. up to 6 tablets per attack or 10 tablets/wk Rectal suppository 0. or uncontrolled hypertension. 300 mg/d SC 6 mg as a single dose. collagen. after 1 h. Subcutaneous sumatriptan produces more adverse effects than the oral drugs. and drowsiness). Maximum. Ergot preparations relieve migraine by constricting blood vessels. 10 or 20 mg by unit-dose spray device. Ergotamine is most effective when given sublingually or by inhalation at the onset of headache. then 0. then 1 tablet q30 min. 12. which have similar adverse effects (eg. 1200 mg CS. with subcutaneous sumatriptan acting the most rapidly and starting to relieve migraine headache within 10 minutes.5 tablet q30 min. repeat in 1 h. in two to four divided doses. Maximum. repeated. sublingually. and to promote the “shock-absorbing” quality of cartilage (by retaining water). a supplement extracted from animal cartilage or manufactured synthetically and used to treat arthritis. These drugs are considered safer than ergot alkaloids. if necessary. the drugs are contraindicated in clients with a history of angina pectoris. which contains water (65 to 80%). to a maximum of 6 inhalations/24 h Adults: PO 2 tablets at onset of migraine. 0. peripheral vascular disease.5 mg as a single dose. Dihydroergotamine mesylate (DHE 45) is a semisynthetic derivative of ergotamine that is less toxic and less effective than the parent drug. The daily dose is based on the client’s weight: under 120 lbs. an NSAID. . 12 mg/d Nasal spray 5. Chondroitin is a normal component of joint cartilage. to a maximum of 6 mg/24 h or 10 mg/wk Inhalation. maximum dose 2 mg. For a few supplements. and severe infections. if necessary. such usage is anecdotal and unsupported by clinical studies. if necessary. metabolism of rizatriptan and zolmitriptan produces active metabolites. In addition. repeat after 2 h if necessary. many herbal medicines are used to relieve pain and/or inflammation.5 mg/24h Naratriptan (Amerge) PO 1–2. 120 to 200 lbs. Ergotamine tartrate (Ergomar) is an ergot alkaloid used only in the treatment of migraine. Ergotamine tartrate and caffeine (Cafergot) is a commonly used antimigraine preparation.36 mg (one inhalation) at onset of migraine. The drugs vary in onset of action. coronary artery disease. Herbal and Dietary Supplements In addition to the drugs described above. to a maximum of three tablets IM 1 mg at onset of migraine. For most of these (eg. proteoglycans. to a total of 3 mg IV 1 mg. in 146 clients with osteoarthritis of the knee. primrose).

you should continue taking the aspirin if Celebrex. However. If pregnant. ✔ Taking a medication for fever is not usually recommended unless the fever is high or is accompanied by other symptoms. ibuprofen. which can cause the tablet to dissolve in the stomach. If you are taking aspirin or an NSAID regularly for pain or inflammation. difficulty breathing. do not chew or crush. ibuprofen. Advil. another one may work because people vary in responses to the drugs. When taken for pain. ✔ Drink 2–3 quarts of fluid daily when taking an NSAID regularly. ✔ Swallow enteric-coated aspirin (eg. or similar drugs. ulcer. ✔ Avoid or minimize alcoholic beverages because alcohol increases gastric irritation and risks of bleeding. ✔ Inform any health care provider if taking aspirin. nose bleed. do not chew or crush. do not take with an antacid. hives) or severe GI symptoms (eg. Sine-Aid IB). Aspirin is as effective as the more costly NSAIDs. avoid OTC products containing ibuprofen (eg. and using the following precautions can increase safety in using these drugs: 1. Most preparations . The coating is applied to decrease stomach irritation by making the tablet dissolve in the intestine. ✔ Inform health care providers if you have ever had an allergic reaction (eg. such as arthritis. ✔ With NSAIDs. to prevent heart attack and stroke. do not take aspirin for approximately 2 weeks before the estimated delivery date. dizziness. Vanquish). severe stomach upset. Because these drugs are so widely used and available. or if new symptoms develop. or Bextra is prescribed. do not combine the OTC products with each other or with aspirin. any combination of these drugs could constitute an overdose. Aspirin. contact a health care provider. improvement may occur within 24 to 48 hours with aspirin and 1 to 2 weeks with other NSAIDs.CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 111 CLIENT TEACHING GUIDELINES Acetaminophen. Bufferin. ask a health care provider. Ecotrin. Arthritis Pain Formula. Also. Improvement of symptoms depends on the reason for use. 2. OTC naproxen is the same as prescription Naprosyn. or naproxen (Aleve). store aspirin in a closed childproof container and keep out of children’s reach. or any other NSAID regularly. blood in urine or stools). fever. Tylenol). This advantage of NSAIDs may be minimal if high doses are taken. ketoprofen or Oruvail extended release capsules. and other NSAIDs with a full glass of liquid and food to decrease stomach irritation. Excedrin. reading product labels. It may be taken on an empty stomach. There are two exceptions if you are taking a small dose of aspirin daily (usually 81–325 mg). there is a high risk of overdosing on different products containing the same drug or products containing similar drugs. if unsure whether the medicine you are taking is long-acting. Motrin) are used to relieve pain. Rofecoxib (Vioxx) and meloxicam (Mobic) may be taken without regard to food. difficulty in breathing. ✔ Swallow any long-acting pills or capsules whole. ibuprofen. Second. Motrin IB. ringing in ears. These drugs are available as both prescription and OTC products. generally avoid taking additional aspirin in over-the-counter (OTC) aspirin or products containing aspirin (eg. The Food and Drug Administration requires an alcohol warning on the labels of OTC pain and fever relievers and urges people who drink three or more alcoholic drinks every day to ask their doctors before using the products. if one is not effective. Ascriptin. but is more likely to cause stomach irritation and bleeding problems. Fever is one way the body fights infection. Knowing drug names. Midol. bruising. Alka-Seltzer. vomiting blood. naproxen delayed-release (EC-Naprosyn) or controlled-release (Naprelan) tablets. Acetaminophen ✔ Acetaminophen is often the initial drug of choice for relieving mild-to-moderate pain and fever because it is effective and does not cause gastric irritation or bleeding. OTC ketoprofen is the same as prescription Orudis. or swelling and weight gain. If these symptoms persist or worsen. This decreases gastric irritation and helps to maintain good kidney function. Anacin. when taken for inflammatory disorders. ✔ Do not take OTC ibuprofen more than 3 days for fever or 10 days for pain. ✔ Acetaminophen is an effective aspirin substitute for pain or fever but not for inflammation or preventing heart attack or stroke. it is generally safe to take occasional doses of aspirin or an NSAID for pain or fever. and inflammation. Ecotrin) whole. Vioxx. Note: These are prescription drugs and most are also available in short-acting products. OTC ibuprofen is the same medication as prescription Motrin. ketoprofen (Actron. ✔ Report signs of bleeding (eg. etodolac (Lodine XL). Also. Doan’s Pills/Caplets. Dristan Sinus. Orudis KT). ✔ Avoid aspirin for approximately 2 weeks before and after major surgery or dental work to decrease the risk of excessive bleeding. Midol IB. the drugs usually act within 30 to 60 minutes. bleeding) after taking aspirin. First. and Other NSAIDs General Considerations ✔ Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil. These include diclofenac sodium (Voltaren or Voltaren XR). ✔ Acetaminophen is available in its generic form and with many OTC brand names (eg. skin rash or hives. If you are taking any prescription NSAID regularly. Recommended doses are smaller for OTC products than for prescription drugs. diflunisal (Dolobid). Self-Administration ✔ Take aspirin. asthma. ✔ To avoid accidental ingestion and aspirin poisoning.

Opponents question the quality of the studies. These patients took 1500 mg of glucosamine sulfate or placebo once a day for 3 years. aspirin) or an anticoagulant (eg. other studies indicate little or no benefit when glucosamine is compared with placebo. The researchers concluded that significant improvement of symptoms and less joint deterioration occurred in clients receiving glucosamine. A study of 212 patients with knee OA indicated that longterm use of glucosamine improves symptoms and prevents changes in joint structure. 10 days in adults. They also state that little is known about long-term toxicity of the compound. Most studies have been done with glucosamine sulfate (GS). ✔ Do not exceed recommended duration of use (longer than 5 days in children. and sinus remedies contain acetaminophen. but more studies are needed. all consumers should read product labels carefully to avoid taking the drug in several products. The rationale for taking supplementary glucosamine is to reduce cartilage breakdown and improve cartilage production and repair. prostaglandin synthesis. Thus. 1000 mg GS. An adequate fluid intake helps prevent formation of uric acid kidney stones. drug’s structural similarity to heparin. Its main active ingredient is thought to be parthenolide. especially in reducing the incidence and severity. asters. Most studies are criticized as being too small. . Feverfew is thought to inhibit platelet aggregation. This prevents or minimizes acute attacks of gout. Glucosamine. radiographs of the knees were taken before starting glucosamine and after 1 and 3 years of treatment. or 3 days for fever in adults and children) without consulting a physician. when uric acid levels in the blood are high and large amounts of uric acid are being excreted in the urine. For example. commercial preparations are not standardized and may contain different amounts of parthenolide. a synthetic supplement. do not take more than 4000 mg (eg. ✔ Avoid or minimize alcoholic beverages because alcohol increases risk of liver damage. 1500 mg GS. and diarrhea occur) when joint pain starts. but there is a potential for increasing risks of bleeding in clients taking an antiplatelet drug (eg. because of its large molecule size. In addition. ✔ Drink 2–3 quarts of fluid daily with antigout drugs. warfarin). and whether it is able to reach cartilage cells. almost all OTC pain relievers (often labeled “nonaspirin”) and cold. or daisies. vomiting. eight 500 mg or extrastrength tablets or capsules) daily. chrysanthemums. People who have hepatitis or other liver disorders and those who ingest alcoholic beverages frequently should take no more than 2000 mg daily. which is the preferred form. pain is usually relieved in 4–12 hours with IV administration and 24–48 hours with oral administration. Aspirin. of too short duration. Glucosamine is an essential structural component of joint connective tissue. carry the drug and start taking it as directed (usually one pill every hour for several hours until relief is obtained or nausea. and Other NSAIDs (Continued ) contain 500 mg of drug per tablet or capsule. but there have been no reports of bleeding from the use of CS. Feverfew is an herbal medicine with some evidence of effectiveness in migraine. in osteoarthritis). Antigout Drugs ✔ When colchicine is taken for acute gout. 650–1000 mg may be taken three or four times daily. Dosage is based on the client’s weight: under 120 lbs. and of having flawed designs. with potential overdoses. Some reviewers of this study said the pain relief was minor and the radiographic changes were insignificant and did not indicate improvement in disease progression. Fluid intake is especially important initially. Larger doses may cause life-threatening liver damage. clients should be encouraged to try standard methods of preventing and treating migraine before taking products with uncertain benefits and risks. possibly as well as NSAIDs. In general. ✔ When allopurinol is taken. over 200 lbs. is also taken for arthritis. The usual recommended dose is 25 to 50 mg daily with food. The Food and Drug Administration requires an alcohol warning on the labels of OTC pain and fever relievers and urges people who drink three or more alcoholic drinks every day to ask their doctors before taking products containing acetaminophen. blood levels of uric acid usually decrease to normal range within 1–3 weeks. and joint cartilage deteriorates. For daily. ✔ With colchicine for chronic gout. synovial fluid becomes thin and less effective in lubricating the joint. There is controversy about glucosamine’s ability to affect cartilage structure and delay joint deterioration. Adverse effects include hypersensitivity reactions in people who are allergic to ragweed. long-term use (eg. 120 to 200 lbs. No interactions with OTC or prescription drugs have been reported. Inflammation and edema may not decrease for several days. flu. It is contraindicated in pregnant and lactating women. With osteoarthritis (OA). For occasional pain or fever. glucosamine production is decreased. whether CS is absorbed systemically. Glucosamine is available as a hydrochloride salt and as a sulfate salt.112 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM CLIENT TEACHING GUIDELINES Acetaminophen. The total daily dosage is usually taken with food in two to four divided doses. but its exact mechanism in migraine prophylaxis is unknown. and the release of inflammatory mediators such as histamine. and stopping the preparation abruptly can result in withdrawal symptoms of pain and stiffness. ✔ Do not exceed recommended doses. Some studies indicate that glucosamine may decrease mild to moderate OA pain in some patients. 2000 mg GS.

Fluid intake is especially important initially when serum uric acid levels are high and large amounts of uric acid are being excreted. impaired blood supply. Glucosamine and chondroitin can each be used alone. • Assist clients with migraine to identify and avoid “triggers.3°C] are usually considered fever). dry skin. This decreases gastric irritation and helps to maintain good kidney function. and inflammation: • Treat the disease processes (eg. less pain. sprains). • Interview and observe regarding mobility and activity levels. nausea. No interactions with OTC or prescription drugs have been reported. • • • • • • Evaluation • Interview and observe regarding relief of symptoms.CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 113 There are no known contraindications to the use of glucosamine. • With acute musculoskeletal injuries (eg. 6). fever. fluids help to prevent precipitation of salicylate crystals in the urinary tract. renal insufficiency) • Deficient Knowledge: Therapeutic and adverse effects of commonly used drugs • Deficient Knowledge: Correct use of OTC drugs for pain. epigastric pain. With arthritis or other musculoskeletal disorders. especially in children • Experience fewer and less severe attacks of migraine Interventions Implement measures to prevent or minimize pain. and pain or tenderness. • Activity Intolerance related to pain • Risk for Poisoning: Acetaminophen overdose • Risk for Injury related to adverse drug effects (GI bleeding. relaxation techniques. Use distraction. or inflammation • Treat pain as soon as possible. with the same dosages as listed above. but it should be avoided during pregnancy and lactation and in children. The American College of Rheumatology and the Arthritis Foundation do not recommend the use of these supplements because they do not believe reported research studies adequately demonstrate significant relief of symptoms or slowing of the disease process. other nonpharmacologic techniques along with drug therapy. infection.6°F [37. assess for pain and limitations in activity and mobility. When questioned by clients. some physicians suggest taking the supplement for 3 months (glucosamine 500 mg and chondroitin 400 mg 3 times a day) and decide for themselves whether their symptoms improve (eg. Apply for approximately 20 minutes. Assess for inflammation. swelling. arthritis) or circumstances (eg. early treatment may prevent severe pain and anxiety and allow the use of milder analgesic drugs. poor positioning or body alignment) thought to be causing pain. and inflammation. antipyretic. lack of physical activity. or kidney disorders. elevated white blood cell count (leukocytosis). Assess for history of peptic ulcer disease. and skin rash. reduced urine output. heat. fever.” Assist clients to drink 2 to 3 L of fluid daily when taking an NSAID regularly. As with studies of the individual components. such as location. but are more often taken in combination. flushed face. Nursing Process Assessment • Assess for signs and symptoms of pain. Use of this combination greatly increased after it was highly praised in The Arthritis Cure by J. then remove. drowsiness. These organizations say longer clinical trials with larger groups of people are needed. and weakness. Ask about allergic reactions to aspirin or NSAIDs. heartburn. duration. systemic signs include fever. effective use of the drugs. GI bleeding. • severity. With antigout drugs. Hot. cold applications can decrease pain. Assess for fever (thermometer readings above 99. With long-term use of aspirin. and inflammation Planning/Goals The client will: • Experience relief of discomfort with minimal adverse drug effects • Experience increased mobility and activity tolerance • Inform health care providers if taking aspirin or an NSAID regularly • Self-administer the drugs safely • Avoid overuse of the drugs • Use measures to prevent accidental ingestion or overdose. assess severity and patterns of occurrences. constipation. Nursing Diagnoses • Acute Pain • Chronic Pain • Interview and observe regarding safe. and concentrated urine may accompany fever if the person also is dehydrated. when appropriate. Theodosakis. because effects are unknown. fever. Local signs are redness. improved ability to walk) and whether they want to continue. headache. With migraine. Adverse effects include GI upset (eg. fluids help to prevent precipitation of urate crystals and formation of urate kidney stones. diarrhea). or antiinflammatory drugs and herbal or dietary supplements. Ask about use of OTC analgesic. . edema. and factors that cause or relieve the pain (see Chap. many of the studies involving glucosamine and chondroitin are flawed. • Select drugs appropriately.

or inflammation is present.5 mg of frovatriptan. Sumatriptan can be taken by mouth.and long-term therapy of conditions characterized by pain and inflammation. and daily use for antiplatelet effects. aspirin must be used appropriately to maximize therapeutic benefits and minimize adverse reactions. fever. which can be taken with fluids. aspirin is effective across a wide range of clinical conditions. numbness. or weakness of the arms and legs. If symptoms recur. ✔ For moderate to severe migraine attacks. The medications used to relieve acute migraine can constrict blood vessels. 5. a regular schedule of administration. tell your prescribing physician immediately and do not take any additional doses without specific instructions to do so. With ergot preparations. For inflammation. aspirin is taken when the pain occurs and is often effective within a few minutes. the high doses and frequent administration required for anti-inflammatory effects increase the risks of GI upset. serious. raise blood pressure. by heart disease or hypertension). to prevent development of more severe symptoms. To avoid potentially serious adverse effects. face or lips. 4. and cause serious adverse effects. ✔ With triptans. potentially fatal reactions may occur. aspirin. shortness of breath. a second dose may be taken. enteric-coated tablets may be better tolerated. 3. ✔ For mild or infrequent migraine attacks. For the nasal spray. For chronic pain. Lower-than-average doses are needed for clients with low serum albumin levels because a larger proportion of each dose is free to exert pharmacologic activity. swelling of eyelids. or nasal spray. codeine) or given between opioid doses. do not exceed recommended doses. 7. ulceration. long-term use in arthritis. ✔ If you have frequent or severe migraine attacks. 5 mg of naratriptan. However. If symptoms of an allergic reaction (eg. and in an orally disintegrating tablet. For pain. be sure to give in fatty tissue under the skin. . wheezing.5 mg of almotriptan. For acute pain or fever. when possible. If self-administering injectable sumatriptan. the usual dose is one spray into one nostril. aspirin is useful in both short.114 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM CLIENT TEACHING GUIDELINES Drugs for Migraine General Considerations ✔ Try to identify and avoid situations known to precipitate acute attacks of migraine. Instructions should be strictly followed for the prescribed method of administration. the drug of first choice is probably sumatriptan (Imitrex) or a related drug. Rizatriptan is available in a regular tablet. take oral drugs (except for rizatriptan orally disintegrating tablets) with fluids. For more severe pain. Self-administration ✔ Take medication at onset of pain. however. acetaminophen. If symptoms return. such as rheumatoid arthritis or osteoarthritis. Like any other drug. or hives) occur after taking a triptan drug. Although effective. heart pounding. injection. aspirin is contraindicated because of its association with Reye’s syndrome. In children. or 10 mg of zolmitriptan in any 24-hour period. such as every 4 to 6 hours. plain aspirin tablets are preferred. Some guidelines include the following: 1. is more effective. Low doses are used for antiplatelet effects in preventing arterial thrombotic disorders such as myocardial infarction or stroke. This drug must not be taken intravenously. or a second dose of naratriptan sooner than 4 hours after the first dose. so such use is rational. For acute pain. For fever. or another nonsteroidal anti-inflammatory drug may be effective. a second spray may be taken 2 hours or longer after the first spray. report signs of poor blood circulation. Aspirin and opioid analgesics act by different mechanisms. For chronic pain. aspirin is useful alone when the discomfort is of low to moderate intensity. and bleeding. However. which can be dissolved on the tongue and swallowed without fluids. Do not take more than 12. Larger doses are needed for anti-inflammatory effects than for analgesic and antipyretic effects. These are symptoms of ergot toxicity. consult a physician about medications to prevent or reduce the frequency of acute attacks. Aspirin dosage depends mainly on the condition being treated. one of these drugs should not be taken if an ergot preparation has been taken within the previous 24 hours. ✔ ✔ ✔ ✔ PRINCIPLES OF THERAPY Guidelines for Therapy With Aspirin When pain. Rectal suppositories are sometimes used when oral administration is contraindicated. if not contraindicated (eg. aspirin is effective if drug therapy is indicated. such as tingling sensations or coldness. ✔ Never take an antimigraine medication prescribed for someone else or allow someone else to take yours. Do not take more than 40 mg of nasal spray or 200 mg orally or by injection in any 24-hour period. aspirin may be combined with an oral opioid (eg. 2. The tablet should be removed from its package with dry hands and placed on the tongue immediately. skin rash. do not take a second dose of sumatriptan or zolmitriptan sooner than 2 hours after the first dose.

When the drug may still be in the GI tract. confusion. and causing drug accumulation. and pregnant women (because aspirin is associated with several maternal and fetal disorders. prolonging the serum halflife. elderly adults with impaired renal function (because aspirin and NSAIDs may cause further impairment). Thus. Toxicity: Salicylate Poisoning Salicylate intoxication (salicylism) may occur with an acute overdose or chronic use of therapeutic doses. IV fluids are indicated when high fever or dehydration is present. lead to gastric ulceration and bleeding. Two major advantages over aspirin are that acetaminophen does not cause gastric irritation or increase the risk of bleeding. decreased hearing. ibuprofen and indomethacin may increase serum levels. Ibuprofen.CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 115 6. seizures) indicates life-threatening toxicity. With ACE inhibitors. Guidelines for Therapy With NSAIDs Nonaspirin NSAIDs are widely used and preferred by many people because of less gastric irritation and GI upset. and naproxen are available by prescription and OTC. With anticoagulants. stopping the drug or reducing the dose is usually sufficient. blood urea nitrogen and serum creatinine should be checked approximately 2 weeks after starting any of the agents. Recognition: Signs and Symptoms Manifestations of salicylism include nausea. visual changes. compared with aspirin. With diuretics. which allows unopposed pressor systems to produce hypertension. which has no effect or may decrease serum lithium levels). and diuretics. including adverse or toxic effects. gastric lavage and activated charcoal help reduce absorption. drowsiness. coma. Treatment In mild salicylism. especially the higher doses taken for anti-inflammatory effects. Because NSAIDs lead to renal impairment in some clients. Prevention To decrease risks of toxicity. Despite its high degree of safety when used appropriately. Many NSAIDs are prescription drugs used primarily for analgesia and anti-inflammatory effects in arthritis and other musculoskeletal disorders. Chronic ingestion of large doses saturates a major metabolic pathway. serum drug levels and risk of toxicity may be increased (except with sulindac. Guidelines for Therapy With Acetaminophen Acetaminophen is effective and widely used for the treatment of pain and fever. they are not prescribed therapeutically for antiplatelet effects. decreased antihypertensive effects are attributed to NSAID inhibition of renal prostaglandin synthesis. The kidneys and myocardium may also be damaged. and hemodialysis effectively removes salicylates from the blood. increasing urinary excretion. hyperventilation. beta blockers. NSAIDs increase effects of a variety of drugs. Therapeutic levels are 150 to 300 mcg/mL. serum drum levels and pharmacologic effects. Clients must be instructed to avoid combined use of prescription and nonprescription NSAIDs because of the high risk of adverse effects. probably because of sodium and water retention. decreased effects on hypertension and edema are attributed to retention of sodium and water. may be increased. Intravenous (IV) sodium bicarbonate produces an alkaline urine in which salicylates are more rapidly excreted. acetaminophen is probably not the drug of choice for people with hepatitis or other liver disorders or those who drink substantial amounts of alcoholic beverages. and correcting fluid. Celecoxib and meloxicam apparently do not increase methotrexate toxicity. Severe central nervous system dysfunction (eg. It is the drug of choice for children with febrile illness (because of the association of aspirin with Reye’s syndrome). severe toxic effects may occur at levels > 400 mcg/mL. delirium. including bleeding). stomatitis. there are decreased antihypertensive effects. vomiting. In severe salicylate overdose. With lithium. thereby slowing drug elimination. With methotrexate. stupor. risks of toxicity (eg. fluid and electrolyte deficiencies. In general. treatment is symptomatic and aimed at preventing further absorption from the GI tract. With digoxin. The major drawback to acetaminophen use is potentially fatal liver damage with overdose. and acid–base imbalances. prothrombin time may be prolonged and risks of bleeding are increased by NSAID-induced gastric irritation and antiplatelet effects. The specific content of IV fluids depends on the serum electrolyte and acid–base status. and prolonged use may . electrolyte. With cyclosporine. With phenytoin. The COX-2 inhibitors have little effect on platelet function. However. several are approved for more general use as an analgesic or antipyretic. not for the life of the platelet (approximately 1 week) as aspirin does. With beta blockers. tinnitus. clients taking low-dose aspirin to prevent myocardial infarction or stroke should continue the aspirin if prescribed a COX-2 inhibitor NSAID. nephrotoxicity) may be increased. fever. NSAIDs inhibit platelet activity only while drug molecules are in the bloodstream. ketoprofen. and others. plasma salicylate levels should be measured when an acute overdose is suspected and periodically when large doses of aspirin are taken long term. bone marrow suppression. NSAIDs commonly cause gastric mucosal damage. nephrotoxicity associated with both drugs may be increased. Effects of NSAIDs on Other Drugs NSAIDs decrease effects of ACE inhibitors. Signs of salicylate toxicity occur at serum levels > 200 mcg/mL.

For clients whose pain is inadequately relieved by acetaminophen. Potentially fatal hepatotoxicity is the main concern and is most likely to occur with doses of 20 g or more. Plasma acetaminophen levels should be obtained when an overdose is known or suspected. At 24 to 48 hours. and today she fainted. For acetaminophen poisoning. coma. oral chondroitin and glucosamine. 24) or hyaluronic acid (eg. and CNS stimulation with excitement and delirium. physical therapy. and death. Synvisc. Acetaminophen is probably the initial drug of choice. from all sources. short-term ingestion of usual therapeutic doses may cause hepatotoxicity and it is recommended that they ingest no more than 2 g daily. recovery in nonfatal overdoses occurs in 7 to 8 days. symptoms may subside but tests of liver function (eg. the FDA may strengthen the warning on products containing acetaminophen and emphasize that the maximum dose of 4 g daily. they should avoid acetaminophen or ask a physician before using even small doses. and sinus remedies). another drug may be tried. Recognition: Signs and Symptoms Early symptoms (12 to 24 hours after ingestion) are nonspecific (eg. Guidelines for Treating Arthritis The primary goals of treatment are to control pain and inflammation and to minimize immobilization and disability. Another recommendation is to limit duration of use (5 days or less in children. The drug provides cysteine. Whynn. Later manifestations may include jaundice. If therapeutic benefits occur. if no benefits seem evident or toxicity occurs. and 3 days in both adults and children when used to reduce fever) unless directed by a physician. Glutathione combines with a toxic metabolite and decreases hepatotoxicity if acetylcysteine is given. and drugs are used to attain these goals. Rest. she has been feeling weak and tired. 10 days or less in adults. about 90% of clients develop liver damage. 2). she swims and uses moist heat to decrease stiffness and discomfort. OTC cold. A drug may be given for 2 or 3 weeks on a trial basis. She asks you if this could be related to the medications she is taking and what she should do. a 73-year-old widow. it is usually given orally (dosage is listed with other antidotes in Chap. Because of multiple reports of liver damage from acetaminophen poisoning. Also. Osteoarthritis (OA) The main goal of drug therapy is relief of pain. Additional treatments for knee OA include topical capsaicin. bilirubin. Metabolism of acetaminophen produces a toxic metabolite that is normally inactivated by combining with glutathione. headache. vomiting. she takes ibuprofen 400 mg every 4 hours while awake and prednisone 5 mg daily. additional amounts constitute an overdose. . anorexia. intra-articular injections of corticosteroids (see Chap. diaphoresis) and may not be considered serious or important enough to report or seek treatment. a precursor substance required for the synthesis of glutathione. For chronic alcohol abusers. flu. AST. rather than the larger anti-inflammatory doses given for rheumatoid arthritis. a product that helps restore the “shock-absorbing” Nursing Notes: Apply Your Knowledge Mrs. a mucolytic agent given by inhalation in respiratory disorders. Prevention The recommended maximum daily dose is 4 g for adults. NSAIDs are usually given in analgesic doses for OA. Another may be that people take the drug in several formulations without calculating or realizing that they are taking potentially harmful amounts.116 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Toxicity: Acetaminophen Poisoning Poisoning may occur with a single large dose (possibly as little as 6 g. followed by vascular collapse. Few of these measures prevent or slow joint destruction. With blood levels >300 mcg/mL at 4 hours after ingestion. vomiting. prothrombin time) begin to show increased levels. exercise. She has also experienced dizziness when getting up from bed. For example. Lately. To control the pain. Ingestion of an overdose may be accidental or intentional. If they ingest three or more alcoholic drinks daily. the supply of glutathione is depleted and the toxic metabolite accumulates and directly damages liver cells. nausea. A COX-2 inhibitor may be preferred for clients at high risk of GI ulceration and bleeding. but may be helpful up to 36 hours. Acute renal failure may also occur. Minimal hepatotoxicity is associated with plasma levels of <120 mcg/mL at 4 hours after ingestion or <30 mcg/mL at 12 hours after ingestion. numerous brand names of acetaminophen are available OTC and acetaminophen is an ingredient in many prescription and OTC combination products (eg. In addition. preferably within 4 hours after ingestion and every 24 hours for several days. or chronic ingestion of excessive doses (5 to 8 g/day for several weeks or 3 to 4 g/day for 1 year). although available NSAIDs have comparable effectiveness. but usually 10–15 g). the specific antidote is acetylcysteine (Mucomyst). Acetylcysteine is most beneficial if given within 8 to 10 hours of acetaminophen ingestion. an NSAID is usually given. Treatment Gastric lavage is recommended if overdose is detected within 4 hours after ingestion and activated charcoal can be given to inhibit absorption. the drug may be continued. A contributing factor may be that some people think the drug is so safe that they can take any amount without harm. has severe osteoarthritis. ALT. Peak hepatotoxicity occurs in 3 to 4 days. Ibuprofen and other propionic acid derivatives are often used. should not be exceeded. In overdose situations. It does not reverse damage that has already occurred. Percocet.

the drug has several advantages over opioid analgesics. For mild pain. include corticosteroids and immunosuppressants (see Chap. Nonopioid and opioid analgesics can be given together or alternated. a combination of analgesics is often needed to provide optimal pain relief. In addition. anti-inflammatory doses for RA. children’s doses are measured by teaspoon. The goal of treatment with corticosteroids is to relieve symptoms. fever. When one is given shortly after birth to close a patent ductus arteriosus. with improvement usually evident within 4 to 8 weeks (ie. Methotrexate (MTX). dosage usually ranges between 2 and 6 g daily but should be individualized to relieve symptoms. including greatly increased susceptibility to infection. is given in smaller doses for RA. or tolmetin may be given. nabumetone and piroxicam have long half-lives and must be discontinued approximately 1 week before surgery. Use of Acetaminophen. the goal with immunosuppressants is to relieve symptoms and also slow tissue damage (so-called disease-modifying effects). the fetus’s kidneys may be adversely affected. aspirin or another NSAID may relieve pain and inflammation. For those who cannot take aspirin or a nonselective NSAID because of gastric irritation. apparently because they form less of the toxic metabolite during metabolism of acetaminophen. analgesic doses given for OA. ibuprofen. As with acute pain. such as influenza or chickenpox. flu. Three newer immunosuppressants used to treat RA are etanercept (Enbrel). which is also used in cancer chemotherapy. such as dental extractions and episiotomies. Aspirin is effective but many people are unable to tolerate the adverse effects associated with anti-inflammatory doses. Aspirin is contraindicated for the client receiving chemotherapy that depresses the bone marrow because of the high risk of thrombocytopenia and bleeding. Rheumatoid Arthritis (RA) Acetaminophen may relieve pain. and Other NSAIDs in Children Acetaminophen is usually the drug of choice for pain or fever in children. joint edema. the only injectable NSAID. After surgery. less morning stiffness. hepatic damage. Caution parents and caregivers to ask pediatricians for written instructions on giving acetaminophen to their children. and the drugs should not be given if there are other risk factors for bleeding. One of these drugs may be used alone or given along with methotrexate in clients whose symptoms are inadequately controlled by methotrexate alone. In addition. For children with juvenile rheumatoid arthritis. Perioperative Use of Aspirin and Other NSAIDs Aspirin should generally be avoided for 1 to 2 weeks before and after surgery because it increases the risk of bleeding. Infants’ doses are measured with a dropper. these drugs may be continued and a opioid analgesic added. there is a risk of overdose and hepatotoxicity because acetaminophen is a very common ingredient in OTC cold. rather than the smaller. especially after relatively minor procedures. peptic ulcer disease. The concentrations are different and cannot be given interchangeably. An overdose can occur with large doses of one product or smaller amounts of several different products. For people who cannot take aspirin. Second-line drugs. acetaminophen or an NSAID may be used alone. Aspirin is not recommended because of its association with Reye’s syndrome. surgery. toxicity has occurred when parents or caregivers have given the liquid concentration intended for children to infants. aspirin. 45). for moderate or severe RA. Children seem less susceptible to liver toxicity than adults. Clinical improvement usually occurs within a few weeks. Pediatric indications for use and dosages have not been established for most of the other drugs. Both groups of drugs may cause serious adverse effects. and Other NSAIDs in Cancer Pain Cancer often produces chronic pain from tumor invasion of tissues or complications of treatment (chemotherapy. pain. for moderate to severe pain.CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 117 ability of joint structures). several of the drugs are used to relieve pain. and other serious problems. these drugs prevent sensitization of peripheral pain receptors by inhibiting prostaglandin formation. Reye’s syndrome usually occurs after a viral infection. a life-threatening illness characterized by encephalopathy. and fatigue). Aspirin. naproxen. It is unknown whether MTX has disease-modifying effects or just improves symptoms and quality of life. When an NSAID is given during late pregnancy to prevent premature labor. the neonate’s kidneys may be adversely affected. When aspirin is used. has been used in more extensive surgeries. They are especially effective for pain associated with bone metastases. to read the labels of all drug products very carefully. However. Use of Acetaminophen. Most other NSAIDs should be discontinued approximately 3 days before surgery. during which aspirin was given for fever. Ibuprofen also may be given for fever. or radiation). infliximab (Remicade). Caution is needed because of increased risks of bleeding. a selective COX-2 inhibitor NSAID may be preferred. NSAIDs are usually given in larger. and minimize adverse effects. and avoid giving children acetaminophen from multiple sources. About 75% of clients have a beneficial response. or other contraindications. ketorolac. and leflunomide (Arava). another NSAID may be given. Although . Clients who continue to have severe pain and functional impairment despite medical treatment may need knee replacement surgery. maintain therapeutic salicylate blood levels. and pain remedies. bleeding and hematomas may occur. Aspirin. bleeding disorders.

or heart failure. In addition. However. osteoarthritis). Thus. Although it was hoped that these drugs would have protective effects on the kidneys as they do on the stomach. aspirin. Small doses. In addition. peri- . acetaminophen. and other substances. Some authorities do not think drug therapy is indicated. Urate crystals are more likely to precipitate in acid urine. long-term use is not recommended because of GI and renal toxicity associated with chronic inhibition of prostaglandin production. Older adults also are more likely than younger adults to acquire nephrotoxicity with NSAIDs. darkened room. They are also expensive compared with other antimigraine drugs. they should be started approximately 1 week before and continued through the menstrual period. however. and protein binding of aspirin is reduced in renal failure so that blood levels of active drug are higher. Biopsy reports usually indicate inflammatory reactions such as glomerulonephritis or interstitial nephritis. and taking the drug with food or a full glass of water may decrease GI effects. and Other NSAIDs in Older Adults Acetaminophen is usually safe in recommended doses unless liver damage is present or the person is a chronic alcohol abuser. and those with hypertension. and retention of salt and water. menstrual) may also need drug therapy to reduce the incidence and severity of acute attacks. in clients who depend on prostaglandins to maintain an adequate renal blood flow. acetaminophen is nephrotoxic in overdose because it forms a metabolite that attacks kidney cells and may cause necrosis. these metabolites may accumulate in renal failure. including aspirin (650 mg bid) and NSAIDs (ibuprofen 300 to 600 mg tid. aspirin and other NSAIDs can decrease blood flow in the kidneys by inhibiting synthesis of prostaglandins that dilate renal blood vessels. Numerous medications have been used for prophylaxis. sumatriptan and related drugs are effective and they cause fewer adverse effects than ergot preparations.118 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Use of Acetaminophen. ketoprofen 50 to 75 mg bid or tid. or other NSAIDs may be effective. During initial administration of these drugs. Acetaminophen is normally metabolized in the liver to metabolites that are excreted through the kidneys. When renal blood flow is normal. others think that lowering serum uric acid levels may prevent joint inflammation and renal calculi. studies indicate that their effects on the kidneys are similar to those of the older NSAIDs. However. Those for whom the triptans and ergot preparations are contraindicated for acute attacks and those whose attacks are predictable (eg. and other NSAIDs can cause or aggravate renal impairment even though they are eliminated mainly by hepatic metabolism. manifested by proteinuria. and the client should lie down in a quiet. Aspirin is nephrotoxic in high doses. 19). a high fluid intake (to produce approximately 2000 mL of urine per day) and alkaline urine are recommended to prevent renal calculi. Measures to prevent or minimize renal damage include avoiding nephrotoxic drugs when possible. NSAIDs are often effective in migraines associated with menstruation. it should be given at the onset of headache. or pyuria. For example. their synthesis is increased and they protect the kidneys from ischemia and hypoxia by antagonizing the vasoconstrictive effects of angiotensin II. the prostaglandin-blocking effects of aspirin and NSAIDS result in constriction of renal arteries and arterioles. They are usually well tolerated. For frequent (two or more per month) or severe migraine attacks. Aspirin and other NSAIDs are probably safe in therapeutic doses for occasional use as an analgesic or antipyretic. Colchicine also should be given for several weeks to prevent acute attacks of gout while serum uric acid levels are being lowered. those older than 50 years of age. aspirin. For moderate to severe migraine attacks. monitoring renal function. and an NSAID is often prescribed. The role of COX-2 inhibitor NSAIDs in renal impairment is not clear. NSAIDs can also cause kidney damage by other mechanisms. Long-term use increases the risk of serious GI bleeding. Use in Renal Impairment Acetaminophen. including a hypersensitivity reaction that leads to acute renal failure. diabetes. When used to prevent migraine associated with menses. naproxen 250 to 750 mg daily or 250 mg tid). treating the disorders that increase risk of renal damage. Aspirin. stopping the NSAID if renal impairment occurs. prophylactic therapy is needed. People at highest risk from the use of these drugs are those with pre-existing renal impairment. decreased glomerular filtration rate. Guidelines for Treating Hyperuricemia and Gout Opinions differ regarding treatment of asymptomatic hyperuricemia. especially with high doses or long-term use. these prostaglandins have limited activity. or sulfinpyrazone may be given for this purpose. If an ergot preparation is used. When renal blood flow is decreased. Guidelines for Treating Migraine For infrequent or mild migraine attacks. Allopurinol. COX-2 inhibitor NSAIDs may be especially beneficial in older adults because they are less likely to cause gastric ulceration and bleeding. because they are strong vasoconstrictors. adverse effects are relatively minor and usually brief. and maintaining hydration. they should not be taken by people with coronary artery disease or hypertension. older adults have a high incidence of musculoskeletal disorders (eg. probenecid. those taking diuretics. norepinephrine. Although these drugs are usually well tolerated. hematuria. because the drugs may reduce blood flow to the kidneys. reducing dosage. Aspirin is usually safe in the small doses prescribed for prevention of myocardial infarction and stroke (antiplatelet effects). gradual increments. Other prophylactic drugs include propranolol and other beta-adrenergic blocking agents (see Chap. decreased renal blood flow.

not exceeding recommended dosages without consulting a health care provider. alcoholics are at high risk of hepatotoxicity with usual therapeutic doses. Give aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) with a full glass of water or other fluid and with or just after food. . and clients should be assessed for characteristics (eg. possibly in reduced dosage. If a client has been taking an NSAID regularly. Acetaminophen may be given NURSING ACTIONS NURSING ACTIONS Analgesic–Antipyretic–Anti-inflammatory and Related Drugs RATIONALE/EXPLANATION 1. he or she may be more likely to experience impaired liver function. Use in Critical Illness Acetaminophen. Pain is more likely to be treated with injectable opioid analgesics in this population. Home Care Home use of acetaminophen and NSAIDs is extremely widespread. adverse drug effects should be reviewed with clients. older age group. Rofecoxib and meloxicam may be given without regard to food. Breaking the tablets or capsules allows faster absorption. venipuncture. Many people are aware of the drugs’ beneficial effects in relieving pain. the home care nurse may need to assist clients in perceiving a need for additional information and provide that information. naproxen and sulindac may be metabolized more slowly and aggravate hepatic impairment if dosage is not reduced. In cirrhotic liver disease. and drugs such as anticonvulsants and others. Examples include: (1) Enteric-coated aspirin (eg. some authorities recommend a maximum daily dose of 2 g for people with hepatitis (compared with a maximum daily dose of 4 g for people who do not have impaired liver function). Even though food delays absorption and decreases peak plasma levels of some of the drugs. These drugs may be risk factors for renal or hepatic impairment or bleeding disorders. If a client is known to drink alcoholic beverages and take acetaminophen. renal impairment. overuse of the drugs) that increase the risks of adverse effects. In liver impairment. If a client presents with acute renal failure. the effects of NSAIDs on liver function and the effects of hepatic impairment on most NSAIDs are largely unknown. and other NSAIDs are infrequently used during critical illness. IM injections. partly because they are usually given orally and many clients are unable to take oral medications. and increases risks of adverse effects and toxicity from overdose. drawing blood. blood levels of oral sumatriptan and related antimigraine drugs may be high because less drug is metabolized on its first pass through the liver and a higher proportion of a dose reaches the systemic circulation. it is probably safer to give them with food. there is a risk of bleeding from common therapeutic (eg. but they may not be adequately informed about potential problems associated with use of the drugs. Specific suggestions include reading and following instructions on labels of OTC analgesics. they should be used with caution and in lower doses in people with impaired hepatic function or a history of liver disease. (3) Diflunisal (Dolobid) (4) Etodolac (Lodine XL) (5) Indomethacin or Indocin SR (continued ) To decrease gastric irritation.CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 119 Use in Hepatic Impairment Except for acetaminophen. Administer accurately a. For example. including the low doses prescribed for antithrombotic effects. inserting urinary catheters or GI tubes) or diagnostic procedures (eg. cigarette smoking. if a client has a history of taking aspirin. b. Thus. angiography). Do not crush tablets or open capsules of long-acting dosage forms and instruct patients not to crush or chew the products. Acetaminophen can cause fatal liver necrosis in overdose because it forms a metabolite that can destroy liver cells. The hepatotoxic metabolite is formed more rapidly when drugmetabolizing enzymes in the liver have been stimulated by ingestion of alcohol. Thus. For example. Thus. avoiding multiple sources of acetaminophen or NSAIDs (eg. destroys the long-acting feature. In addition. he or she may be more likely to experience renal failure if the critical illness causes dehydration or requires treatment with one or more nephrotoxic drugs. multiple OTC NSAIDs or an OTC and a prescription NSAID). by rectal suppository for pain or fever in clients who are unable to take oral drugs. Because the drugs are metabolized in the liver. the drugs should be used cautiously. Ecotrin) (2) Diclofenac sodium (Voltaren or Voltaren XR). aspirin. NSAID ingestion must be considered as a possible cause.

observe for: (1) Gastrointestinal problems—anorexia.120 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM NURSING ACTIONS (6) Ketoprofen or Oruvail extended-release capsules (7) Naproxen delayed-release (EC-Naprosyn) or naproxen sodium controlled-release (Naprelan) c. Renal damage is usually reversible when the drug is discontinued. ataxia. vomiting. and observe for a decrease. and stiffness of joints. record temperature every 2 to 4 hours. c. e. Therapeutic effects occur within 4–12 hours after intravenous colchicine administration and 24–48 hours after oral administration. increased blood urea nitrogen (BUN). Serum uric acid levels usually decrease to normal range within 1–3 weeks. bleeding. d. fenoprofen. hyperkalemia. hematuria. g. When the above drugs are given for chronic gout. When allopurinol. 3. With most of the NSAIDs. More likely to occur in people with preexisting renal impairment. These effects may simulate asthma in people who are allergic to aspirin and aspirin-like drugs. melena. including potentially fatal bronchospasm. (2) Hematologic problems—petechiae. indomethacin. Tinnitus (ringing or roaring in the ears) is a classic sign of aspirin overdose (salicylate intoxication). May result in severe symptoms. naproxen. and normal serum uric acid levels. 1–2 weeks may be required before beneficial effects become evident. When triptans or ergot preparations are given in migraine headache. diarrhea. When colchicine is given for acute gouty arthritis. dermatitis (5) Hypersensitivity reactions with dyspnea. or sulfinpyrazone is given for hyperuricemia. Give antimigraine preparations at the onset of headache. Older adults are at greater risk because of decreased renal blood flow and increased incidence of congestive heart failure and diuretic therapy. observe for decreased pain. Observe for adverse effects a. anemia) (3) Central nervous system effects—headache. epistaxis. These are common reactions. observe for decreased pain and inflammation in involved joints. f. etodolac. With analgesic–antipyretic–anti-inflammatory and antigout agents. Pain relief is usually evident within 30–60 minutes. When drugs are given for fever. improvement is usually noted within 24–48 hours. When drugs are given for pain. more likely with aspirin. celecoxib. rofecoxib. especially when fluid intake is decreased or fluid loss is increased. fainting. Observe for therapeutic effects a. especially with high dosages. redness. retention of sodium and water with resultant edema . absence of new tophi. dizziness. and bone marrow depression (leukopenia. observe for decreased or absent manifestations of pain. increased serum creatinine. confusion. ulceration RATIONALE/EXPLANATION To prevent development of more severe symptoms. skin rashes These effects are relatively common with indomethacin and may occur with most of the other drugs. and valdecoxib. Most likely to occur in patients with a history of nasal polyps. colchicine. (continued ) (6) Tinnitus. ibuprofen. sulindac. Also observe for increased joint mobility and exercise tolerance. 2. bruises. thrombocytopenia. especially with overdosage. It occurs with NSAIDs as well. diflunisal. Bone marrow depression is more likely to occur with colchicine. blurred vision (7) Nephrotoxicity—decreased urine output. probenecid. tolmetin. decreased joint pain and increased joint mobility. and sulfinpyrazone and less likely with acetaminophen. insomnia. With aspirin. asthma. bronchospasm. edema. nausea. or rhinitis. observe for decreased size of tophi. piroxicam. observe for relief of symptoms. When drugs are given for arthritis and other inflammatory disorders. Therapeutic effects are usually evident within 15–30 minutes. drowsiness (4) Skin rashes. observe for normal serum uric acid level (approximately 2–8 mg/100 mL). b. Edema may not decrease for several days. heat.

Additive analgesic effects because of different mechanisms of action. (3) Hypertension (4) Hypersensitivity reactions—local edema and pruritus. Drugs that decrease effects of aspirin and other NSAIDs: (1) Alkalinizing agents (eg. paresthesias c. Allergic reactions are relatively uncommon. dizziness. Blood pressure may rise as a result of generalized vasoconstriction induced by the ergot preparation. chronic poisoning is usually a result of overdosage. poisoning may be acute or chronic. (9) Hepatotoxicity—liver damage or failure b. prednisone) b. weak pulse. A few cases have been reported with COX-2 inhibitors. drowsiness. oral (4) Codeine. The ergot alkaloids are highly toxic. anaphylactic shock 4. a prostaglandin. muscle weakness and pain. in overdose or in people with underlying liver disease Most adverse effects are mild and transient. increases serum celecoxib levels Increase rate of renal excretion This drug. vomiting. Additive gastric irritation and possible ulcerogenic effects Inhibits liver enzymes that normally metabolize celecoxib. observe for: (1) Nausea. Large doses also damage capillary endothelium and may cause thrombosis and occlusion. Induces drug-metabolizing enzymes in the liver and decreases blood levels of rofecoxib (continued ) (5) Corticosteroids (eg. numbness. People taking anticoagulants should avoid aspirin and aspirin-containing products. headache. angina-like chest pain. With triptan antimigraine drugs. convulsions. vomiting. probably due to retention of sodium and water. and tingling of the extremities. dizziness. cyanosis. Drug that increases effects of celecoxib: (1) Fluconazole (and possibly other azole antifungal drugs) c. mechanism unknown. fatigue. nausea. Induces drug-metabolizing enzymes in the liver and decreases blood levels of fenoprofen. transient tachycardia or bradycardia. Dosage of fenoprofen may need to be increased if phenobarbital is started or decreased if phenobarbital is discontinued. diarrhea (2) Symptoms of ergot poisoning (ergotism)—coolness. sodium bicarbonate) (2) Misoprostol (Cytotec) d. was developed specifically to prevent aspirin and NSAID-induced gastric ulcers. Drugs that increase effects of aspirin and other NSAIDs: (1) Acidifying agents (eg. gangrene of the extremities These drugs have a direct effect on the vomiting center of the brain and stimulate contraction of gastrointestinal smooth muscle. Observe for drug interactions a. because of their vasoconstrictive effects. hypertension.CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 121 NURSING ACTIONS (8) Cardiovascular effects—increased hypertension RATIONALE/EXPLANATION Long known to occur with older NSAIDs. Drug that decreases effects of rofecoxib (1) Rifampin . confusion. However. Aspirin or an NSAID can often be used with these drugs to provide adequate pain relief without excessive doses and sedation. Gangrene of extremities rarely occurs with usual doses unless peripheral vascular disease or other contraindications are also present. they may cause or aggravate angina pectoris and hypertension. Acute poisoning is rare. observe for: (1) Chest tightness or pain. thirst. hydrocodone. With ergot antimigraine drugs. Occurs mainly with acetaminophen. ascorbic acid) (2) Alcohol (3) Anticoagulants. oxycodone Acidify urine and thereby decrease the urinary excretion rate of salicylates Increases gastric irritation and occult blood loss Increase risk of bleeding substantially. Drug that decreases effects of fenoprofen: (1) Phenobarbital e. Circulatory impairments may result from vasoconstriction and vascular insufficiency.

Review and Application Exercises 1. When patients become volume depleted secondary to the blood loss. persistent hypertension and intracranial hemorrhage (2) Colchicine (3) Diuretics (4) Salicylates i.122 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM NURSING ACTIONS f. Nursing Notes: Apply Your Knowledge Answer: The symptoms may be related to her medications. Increase ulcerogenic effect Increase ulcerogenic effect Increases risk of bleeding. so patients get used to the fatigue. Whynn seeks care promptly. a triptan should not be taken for at least 2 weeks after an MAOI is discontinued. ephedrine. would aspirin or acetaminophen be preferred? Why? 5. Whynn’s postural blood pressure. they can exhibit signs of dizziness and syncope. Indomethacin causes gastric irritation and is considered an ulcerogenic drug. phenylephrine) j. and sulfinpyrazone: (1) Alkalinizing agents (eg. or acetaminophen be preferred? Why? . Drugs that increase effects of ergot preparations: (1) Vasoconstrictors (eg. and acetaminophen. but you need to collect more information before you can be sure. to prevent falls and accidental injury. another NSAID. These drugs should not be used concurrently. (2) Ergot preparations Triptans and ergot preparations should not be taken concurrently or within 24 hours of each other. and if blood is present. How do aspirin and other NSAIDs produce analgesic. ibuprofen. For a 50-year-old adult with rheumatoid arthritis. A very common side effect of aspirin (and all nonsteroidal antiinflammatory drugs) is gastric irritation that can cause gastrointestinal ulceration and bleeding. and antiplatelet effects? 2. Take Mrs. sodium bicarbonate) RATIONALE/EXPLANATION Increase risk of gastrointestinal bleeding. decrease uricosuric effects of probenecid and sulfinpyrazone but do not interfere with the action of allopurinol. Most important. Drugs that decrease effects of indomethacin: (1) Antacids h. anti-inflammatory. Drugs that increase effects of indomethacin: (1) Anticoagulants. will do some diagnostic tests. who will test her stool for blood. 4. Drugs that increase the effects of triptan antimigraine drugs: (1) Monoamine oxidase inhibitors (MAOIs) Increase serum levels of triptans and may cause serious adverse effects. especially with daily ingestion? 3. For a 6-year-old child with fever. Recommended for concurrent use until serum uric acid levels return to normal. Refer her to her physician. Triptans and MAOIs must not be taken concurrently. make sure Mrs. probenecid. Blood loss is often gradual. epinephrine. because severe hypertension and stroke may occur. Delay absorption from the gastrointestinal tract Decrease risks of renal calculi from precipitation of uric acid crystals. including cardiac arrhythmias and myocardial infarction. Salicylates are uricosuric at doses greater than 5 g/day. oral (2) Corticosteroids (3) Salicylates (4) Heparin g. would aspirin. Decreases attacks of acute gout. What adverse effects occur with aspirin and other NSAIDs. Drugs that decrease effects of allopurinol. Alkalinizing agents are recommended until serum uric acid levels return to normal. Additive vasoconstriction with risks of severe. Compare and contrast the uses and effects of aspirin. antipyretic. Decrease uricosuric effects Mainly at salicylate doses of less than 2 g/day.

Textbook of therapeutics: Drug and disease management. L. Whitaker. Springhouse. placebocontrolled trial of glucosamine to control pain in osteoarthritis of the knee. & Barkin. Kelley’s Textbook of internal medicine. A. and acetaminophen? 8. New York: St Martin’s Press. Southern Medical Journal. & Patrono. A. P. (2000). D. J. Lance. & Carr. 433–442. J. In E. p.. T. What is the rationale for combining opioid and nonopioid analgesics in the treatment of moderate pain? 11. October 29–November 2.. selective inhibitors of cyclooxygenase-2. 168. J. PA: Springhouse Corporation. other NSAIDs.. G. A randomized. P. R. If you were a client. W. 94(8). & Avila. Abstract No. what information do you think would be most helpful in home management of migraine? SELECTED REFERENCES Barkin. McAlindon. (1997). The arthritis cure. (2000). When teaching a client about home use of aspirin. Graves. In H. R.). E. Philadelphia: Lippincott Williams & Wilkins. Professional’s handbook of complementary & alternative medicines. W.CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 123 6. Humes (Ed. 1469–1475. & Felson.). (2000). LaValley. Gourley (Eds. Philadelphia: Lippincott Williams & Wilkins. Pharmacologic management of acute and chronic pain. Philadelphia. Approach to the patient with headache. 7th ed. A. pp 667—678. Fitzgerald. R. (1999).” would aspirin. Hughes. J.. What is the rationale for using acetylcysteine in the treatment of acetaminophen toxicity? 10.. other NSAIDs. The coxibs. New England Journal of Medicine. A. Osteoarthritis. R. & Hunder. (2001). C. For a 75-year-old adult with osteoarthritis and a long history of “stomach trouble. Journal of Clinical Hypertension. (Updated monthly). Glucosamine and chondroitin for treatment of osteoarthritis. 283. R. another NSAID. D. M. (Program and abstracts from the 64th Annual Scientific Meeting of the American College of Rheumatology. A. 2836–2844. Journal of the American Medical Association. T. what information must be included? 9. Herfindal & D. I. Louis: Facts and Comparisons. and acetaminophen. C. Theodosakis. 2000. St. 396–398. (2001). (2000). W. What are some nursing interventions to decrease the adverse effects of aspirin. . or acetaminophen be preferred? Why? 7. D. 345(6). 4th ed. 756–812. 2(6). pp. J. Gulin. Worsening of hypertension by cyclooxygenase-2 inhibitors. double-blind. J. E. L. Fetrow. (2000). T.1903). & Small. Drug facts and comparisons.

there is no logical reason to take a combination of the drugs for anxiety. Do not stop taking a Valium-related drug abruptly. cause drowsiness. narcotic analgesics. and how long to take the drugs. brain-depressant drugs should be taken only by those people for whom they are prescribed. falls. Accidental or intentional ingestion may lead to serious adverse effects. and cause dependence. For long-term relief. ✔ Avoid alcohol and other depressant drugs (eg. ✔ Take zolpidem on an empty stomach. An antihistamine that causes drowsiness is the active ingredient in OTC sleep aids (eg. Compoz. This helps avoid multiple prescriptions of drugs with similar effects and reduces the risk of serious adverse effects from overdose. difficulty breathing. including the ability to decrease nervousness. these factors can cancel or decrease the drugs’ effects. . Valium. ✔ Do not perform tasks that require alertness if drowsy from medication. combining them produces additive depression and may lead to excessive drowsiness. which may eventually cause worse problems than the original anxiety or insomnia. driving a car. ✔ Try to identify and avoid factors that cause nervousness or insomnia. When being discontinued. All of the Valium-related drugs. dosage should be gradually reduced. With rare exceptions. zaleplon (Sonata). and zolpidem (Ambien) can cause physical dependence. Do not take “sleeping pills” every night. or to take one drug for daytime sedation and another for sleep. and other potentially serious adverse drug effects. they may be taken with food if stomach upset occurs. how often. ✔ Take buspirone on a daily schedule. and other potentially hazardous tasks. Withdrawal symptoms can occur. such as caffeine-containing beverages and stimulant drugs. ✔ Omit one or more doses if excessive drowsiness occurs to avoid difficulty breathing. sedating herbs such as kava and valerian. over-thecounter [OTC] antihistamines and sleeping pills. as directed and with the supervision of a health care provider. ✔ Take oral benzodiazepines with a glass of water. ✔ Take sleeping pills just before going to bed so that you are lying down when the expected drowsiness occurs. Tylenol PM). especially during the first several days of use. rest. it is ineffective for occasional use. Physical exercise. and relaxation techniques are safer than any drug. counseling or psychotherapy may be more beneficial because it can help you learn other ways to decrease your nervousness and difficulty in sleeping. Thus. Because these drugs depress brain functioning when taken alone. reading. These drugs lose their effectiveness in 2–4 weeks if taken nightly. out of reach of children and adults who are confused or less than alert. If the drugs are used. Avoid smoking. and thereby make routine activities potentially hazardous. is sometimes confused with ranitidine (Zantac). ✔ Inform all health care providers when taking a sedativetype medication. Unisom) and many pain reliever products with “PM” as part of their names (eg. and other adverse drug effects. ✔ Most “nerve pills” and “sleeping pills” belong to the same chemical group and have similar effects. ambulating without help. but there are several others as well. Sominex. Also. These drugs produce more beneficial effects and fewer adverse reactions when used in the smallest effective doses and for the shortest duration feasible in particular circumstances. and Restoril are commonly used examples of this group. These activities may lead to falls or other injuries if undertaken while alertness is impaired. The drugs often impair mental and physical functioning. because a person sedated by a previous dose may take additional doses. Store drugs safely. Alprazolam (Xanax). stress management. Do not share these drugs with anyone else. Stimulant drugs include asthma and cold remedies and appetite suppressants. do not keep the drug container at the bedside. traumatic injuries. operating machinery. Nytol. at bedtime. craft work. Ativan. ✔ Use nondrug measures to promote relaxation.CLIENT TEACHING GUIDELINES Antianxiety and Sedative-Hypnotic Drugs General Considerations ✔ “Nerve pills” and “sleeping pills” can relieve symptoms temporarily but they do not cure or solve the underlying problems. and sleep when possible. ✔ ✔ ✔ ✔ ✔ Self-Administration ✔ Follow instructions carefully about how much. It is not fully effective until after 3–4 weeks of regular use. and the dietary supplement melatonin) while taking any antianxiety or sedative-hypnotic drugs (except buspirone). preferably by the generic and trade names. and cause sleep disturbances when stopped. These mindaltering. This may prevent or decrease the severity of nervousness or insomnia so that sedative-type drugs are not needed. Xanax. these drugs are recommended only for short-term use. because the drug acts quickly to cause drowsiness. a drug for heartburn and peptic ulcers.

Mouth dryness is a common side effect of the drugs. as follows. ✔ Avoid taking these medications with antacids. and use sunscreen lotions. including those available without prescription or those prescribed for another person. or perform activities that require alertness when drowsy from medication. Consistent blood levels are necessary to control symptoms and prevent recurring episodes of acute illness and hospitalization. Drowsiness. Although it is usually not serious. wear protective clothing. to decrease risks of undesirable drug interactions. for heartburn). and impaired muscle coordination are especially likely during the first 2 weeks of drug therapy but tend to decrease with time. because changes in drug therapy may be indicated. if able. keep the client indoors and use air conditioning or fans during the hours of highest heat levels. dry mouth can lead to mouth infections and dental cavities. thorough and frequent toothbrushing. to maintain blood levels and beneficial effects. including dental checkups. operate machinery. slowed thinking. ✔ Practice good oral hygiene. when results can be expected. If an antacid is needed (eg. if dizziness and faintness occur. ✔ Take the medication at bedtime. Antacids decrease absorption of these drugs from the intestine. and the tentative length of drug therapy. . including the desired results. ✔ Maintain an adequate supply of medication to ensure regular administration. ✔ These drugs should be tapered in dosage and discontinued gradually. ✔ Try to prevent the client from taking unprescribed medications.CLIENT TEACHING GUIDELINES Antipsychotic Drugs Antipsychotic drugs are given to clients with schizophrenia. ✔ Avoid exposure to excessive heat. it should be taken 1 hour before or 2 hours after the antipsychotic drug. so that drowsiness aids sleep and is minimized during waking hours. Medication Administration Assist or prompt the client to: ✔ Take medications in the correct doses and at the correct times. they should not be stopped abruptly. Some of these medications may cause fever and heat prostration with high environmental temperatures. to prevent undesirable drug interactions. ✔ Keep all physicians informed about all the medications being taken by the client. a chronic mental illness. Because of the nature of the disease. ✔ Lie down for approximately an hour after receiving medication. ✔ Minimize exposure to sunlight. ✔ Report unusual side effects and all physical illnesses. Alcohol and sleeping pills should be avoided because they may cause excessive drowsiness and decreased awareness of safety hazards in the environment. In hot weather or climates. General Considerations ✔ Ask about the planned drug therapy regimen. a responsible adult caregiver is needed to prompt a client about taking particular doses and to manage other aspects of the drug therapy regimen. ✔ Do not allow the client to drive a car. and frequent mouth rinsing. Sensitivity to sunlight occurs with some of the drugs and may produce a sunburn-type of skin reaction. drinking fluids.

chapter 10 Drugs for Mood Disorders: Antidepressants and Mood Stabilizers Objectives AFTER STUDYING THIS CHAPTER. and sleeps much more than usual. 6. the etiology of depression is unclear. Discuss selected characteristics of bupropion. but they write and call often. This hypothesis stemmed from M 163 . 8. It is likely that depression results from interactions among several complex factors. nefazodone. McGrath and her daughter? MOOD DISORDERS ood disorders include depression. ᮣ What symptoms does Mrs. Discuss interventions to increase safety of lithium therapy. 2. bipolar disorder and mood stabilizing drugs are also discussed. 7. what suggestions would you have for Mrs. adverse effects. THE STUDENT WILL BE ABLE TO: 1. was recently widowed. Monoamine Neurotransmitter Dysfunction Depression is thought to result from a deficiency of norepinephrine and/or serotonin. The average depressive episode lasts about 5 months. She is also reluctant to go out with friends or visit her children. dysthymia. Compare and contrast selective serotonin reuptake inhibitors with tricyclic antidepressants. and venlafaxine. Depression and antidepressant drug therapy are emphasized in this chapter. 3. and having one episode is a risk factor for developing another episode. Analyze important factors in using antidepressant drugs and lithium in special populations. and nursing process implications. McGrath have that may indicate she is depressed? ᮣ What additional data would support a diagnosis of depression? ᮣ At this point. Two of the major theories of depression pathogenesis are described below. Depression is estimated to affect 5% to 10% of adults in the United States and to be increasing in children and adolescents. Describe major features of depression and bipolar disorder. and make major decisions. and treating overdoses of antidepressant drugs and lithium. recognizing. mirtazapine. McGrath seems to be losing weight. 5. Etiology Despite extensive study and identification of numerous potential contributory factors. principles of therapy. Her children live out of state. stays home most of the time. Betty’s daughter calls you because she is concerned about her mother. and cyclothymia (Box 10–1). Describe the use of lithium in bipolar disorder. Discuss characteristics of antidepressants in terms of mechanism of action. bipolar disorder. She depended on her husband to handle their finances. complains she feels very tired. McGrath’s risk for depression. indications for use. 4. Critical Thinking Scenario Betty McGrath. Describe the nursing role in preventing. Mrs. 73 years of age. ᮣ List factors that might increase Mrs. It is associated with impaired ability to function in usual activities and relationships. maintain their home. She enjoyed the role of homemaker and never worked outside the home.

This down-regulation of receptors. and CRF apparently functions as a neuro- . integration. severe or major depression is a psychiatric illness and requires treatment. but relief of depression occurred only after weeks of drug therapy. researchers have identified non-monoamine systems that influence neurotransmission and are significantly altered in depression. such as hallucinations and delusions Dysthymia Dysthymia involves a chronically depressed mood and at least two other symptoms (eg. inflated self-esteem. is characterized by depressed mood. Neuroendocrine Factors In addition to monoamine neurotransmission systems. Mania is characterized by excessive CNS stimulation with physical and mental hyperactivity (eg. poor concentration. insomnia. 4th edition (Text Revision). serotonin. presynaptic receptors regulate the release and reuptake of neurotransmitters. in which people of usually normal moods experience recurrent episodes of depression. lists criteria for a major depressive episode as a depressed mood plus at least five of the following symptoms for at least 2 weeks: Loss of energy. atypical pain) studies demonstrating that antidepressant drugs increase the amounts of one or both of these neurotransmitters in the central nervous system (CNS) synapse by inhibiting their reuptake into the presynaptic neuron. there is increasing awareness that balance. All known treatments for depression lead to the down-regulation of beta receptors and occur in the same period as the behavioral changes associated with antidepressant drug therapy. corresponds with therapeutic drug effects. constant talking. Symptoms must be present for at least two years.164 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM BOX 10–1 TYPES OF MOOD DISORDERS Obsession with death. Overall. Major depression also is categorized as unipolar. Studies demonstrated that chronic drug administration (ie. For example. racing thoughts. thus allowing in- creased norepinephrine release. Serotonin helps regulate several behaviors that are disturbed in depression. grandiose ideas. available antidepressants may increase the sensitivity of postsynaptic receptors and decrease the sensitivity of presynaptic receptors. impulsiveness. It seems apparent that long-term administration of antidepressant drugs produces complex changes in the sensitivities of both presynaptic and postsynaptic receptor sites. thoughts of suicide Psychotic symptoms. but they are less severe. Physiologically. may also play a role. whose secretion is increased in depression. Depression Depression. energy level. overeating. and cognitive and psychomotor functions. and possibly other neurotransmission systems (eg. often described as the most common mental illness. they inhibit the release of norepinephrine. There is evidence that alpha2 receptors are also down-regulated by antidepressant drugs. first noted with beta-adrenergic receptors. or emotional upset. such as mood. or excessive eating and weight gain Sleep disorders (hypersomnia or insomnia) Somatic symptoms (eg. hypersomnia. constipation. short attention span) for at least one week. Cyclothymia Cyclothymia is a mild type of bipolar disorder which involves periods of hypomania and depression that do not meet the criteria for mania and major depression. Symptoms are similar to those of acute psychosis or schizophrenia. appetite. located on presynaptic nerve terminals. It does not usually require drug therapy. Serotonin received increased attention after the selective serotonin reuptake inhibitor (SSRI) antidepressants were marketed. A major non-monoamine is corticotropin releasing factor. poor concentration. low energy. indicate less CNS stimulation and hyperactivity. Bipolar Disorder Bipolar disorder involves episodes of depression alternating with episodes of mania. Emphasis shifted toward receptors because the neurotransmitter view did not explain why the amounts of neurotransmitter increased within hours after single doses of a drug. dopamine. fatigue Indecisiveness Difficulty thinking and concentrating Loss of interest in appearance. CRF-secreting neurons are widespread in the CNS. Although the symptoms may cause significant social and work-related impairments. and last 3 or 4 days. and it occurs in all age groups. low self-esteem. Mild depression occurs in everyone as a normal response to life stresses and losses and usually does not require treatment. or hormone (CRF or CRH). constant movement. postsynaptic receptors participate in the transmission of nerve impulses to target tissues. little need for sleep. and interactions among norepinephrine. work. Researchers identified changes in norepinephrine and serotonin receptors with chronic antidepressant drug therapy. sleep. increased neurotransmitter in the synapse for several weeks) results in fewer receptors on the postsynaptic membrane. agitation. acetylcholine) are probably more important etiologic factors than single neurotransmitter or receptor alterations. feelings of sadness. headache. When these receptors are stimulated. With serotonin receptors. Major Depression The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders. Changes in neurons may also play a major role. Hypomania involves the same symptoms. anorexia. they are not severe enough to meet the criteria for major depression. and leisure and sexual activities Inappropriate feelings of guilt and worthlessness Loss of appetite and weight loss. feelings of hopelessness) for two years. animal studies indicate that serotonin is required for optimal functioning of the neurons that produce norepinephrine. Alpha2-adrenergic receptors (called autoreceptors).

. a postsynaptic receptor. ANTIDEPRESSANT DRUGS Drugs used in the pharmacologic management of depressive disorders are derived from several chemical groups. MAOIs prevent the metabolism of neurotransmitter molecules. Extrahypothalamic CRF is also increased in depression. receptors adapt to the presence of increased neurotransmitter by decreasing their number or sensitivity to the neurotransmitter. the HPA axis and cortisol activity). Secretion of both hypothalamic and extrahypothalamic CRF apparently returns to normal with recovery from depression. With chronic drug administration. Older antidepressants include the tricyclic antidepressants (TCAs) and the monoamine oxidase inhibitors (MAOIs). and cortisol by the adrenal cortex. Most studies have involved early life trauma such as physical or sexual abuse in childhood. which apparently change brain structure and function and contribute to the development of depression in some people. enter the portal circulation. Bipolar Disorder Like depression. This alteration of cortisol receptors takes about two weeks. alteration of monoamine neurotransmitters in several areas of the brain. antidepressant drugs apparently normalize abnormal neurotransmission systems in the brain by altering the amounts of neurotransmitters and the number or sensitivity of receptors. the HPA axis. T lymphocytes and B lymphocytes) produce cytokines (eg. General characteristics of antidepressants include the following: • All are effective in relieving depression. norepinephrine receptors. Genetic factors are considered important mainly because close relatives of a depressed person are more likely to experience depression. especially postsynaptic beta receptors and presynaptic alpha2 receptors. • They are metabolized by the cytochrome P450 enzymes in the liver. Additional Factors Additional factors thought to play a role in the etiology of depression include the immune system. The increased cortisol (part of the normal physiologic response to stress) is thought to decrease the numbers or sensitivity of cortisol receptors (downregulation) and lead to depression. Many antidepressants and other drugs are metabolized by the 2D6 or 3A4 subgroup of the enzymes. such as a relative excess of excitatory neurotransmitters (eg. interleukins. The serotonin2 receptor. absorbed from the small bowel. but they differ in their adverse effects. SSRIs selectively inhibit the reuptake of serotonin. genetic factors. the approximate time interval required for the drugs to improve symptoms of depression. all of which are activated as part of the stress response. antidepressants may interact with each other and with a wide variety of drugs that are normally metabolized by the same subgroups of enzymes. including mild stress or daily life events. and circulate through the liver. Environmental factors include stressful life events. After neurotransmitters are released from presynaptic nerve endings. Immune cells (eg.CHAPTER 10 DRUGS FOR MOOD DISORDERS: ANTIDEPRESSANTS AND MOOD STABILIZERS 165 transmitter and mediator of the endocrine. Changes have been identified in CRF. there is increased secretion of CRF by the hypothalamus. the molecules that are not bound to receptors are normally inactivated by reuptake into the presynaptic nerve fibers that released them or metabolized by monoamine oxidase (MAO). Hypothalamic CRF is part of the hypothalamic-pituitary-adrenal (HPA) axis. Other neuroendocrine factors in depression are thought to include abnormalities in the secretion and function of thyroid and growth hormones. As a result. and behavioral responses to stress as well as a releasing factor for corticotropin. These changes are thought to cause a hypersensitive or exaggerated response to later stressful events. which affect neurotransmission. More specifically. adrenocortiocotropic hormone (ACTH) by the anterior pituitary. and SSRIs. Newer drugs include the selective serotonin reuptake inhibitors (SSRIs) and several individual drugs that differ from TCAs. immune. Drugs that stimulate the CNS can cause manic and hypomanic behaviors that are easily confused with schizophreniform psychoses. where they undergo extensive first-pass metabolism before reaching the systemic circulation. and tumor necrosis factor). and cortisol (glucocorticoid) receptors may also be downregulated. and the noradrenergic neurotransmission system. Possible mechanisms of cytokine-induced depression include increased CRF and activation of the HPA axis. which becomes hyperactive in depression. interferons. MAOIs. • All must be taken for 2 to 4 weeks before depressive symptoms improve. These mechanisms thereby increase the amount of neurotransmitter available to bind to receptors. mania and hypomania may result from abnormal functioning of neurotransmitters or receptors. or cytokines functioning as neurotransmitters and exerting direct effects on brain function. autonomic. are downregulated. Thus. gamma-aminobutyric acid [GABA]). norepinephrine) or a relative deficiency of inhibitory neurotransmitters (eg. This view is supported by animal studies indicating that antidepressant drugs restore the ability of cortisol receptors to bind with cortisol. • They are given orally. and environmental factors. They may also modify interactions among neurotransmission systems and affect endocrine function (eg. Mechanisms of Action Although their actions are still being studied in relation to newer information about brain function and the etiology of mood disorders. Most antidepressants prevent the reuptake of multiple neurotransmitters.

weight loss) and sexual dysfunction (eg. largely because of their potential for serious interactions with certain foods and other drugs. the drugs compete with endogenous compounds and other medications for binding sites. an inhibitory neurotransmitter. Because they are highly lipid soluble. mixed mania and depression. Once absorbed. and drug effects decrease slowly (over 2 to 3 months) when fluoxetine is discontinued. Contraindications to Use Antidepressant drugs are contraindicated or must be used with caution in clients with acute schizophrenia. They are well absorbed after oral administration. a TCA may be given after physical causes (eg. They are well absorbed with oral administration. the exact mechanism of action is unknown. dry mouth. antidepressant effects are attributed to changes in receptors rather than changes in neurotransmitters. Serious. Although some of the drugs act more selectively on one neurotransmission system than another initially. potassium.166 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Thus. orthostatic hypotension. Most also cause some degree of CNS stimulation (eg. If a client on an SSRI is to be transferred to an MAOI. and occur independently of life events. MAOIs are considered third-line drugs. sertraline. and sodium ions for binding sites. Monoamine Oxidase Inhibitors MAOIs are infrequently used. insomnia). Fluoxetine also forms an active metabolite with a half-life of 7 to 9 days. this selectivity seems to be lost with chronic administration. it is known to affect the synthesis. names. indications for use. TYPES OF ANTIDEPRESSANTS AND INDIVIDUAL DRUGS Additional characteristics of antidepressants and lithium are described in the following sections. and have a half-life of 24 to 72 hours. antidepressants are increasingly being used for treatment of anxiety disorders. most SSRIs should be discontinued at least 14 days before starting the MAOI. Indications for Use Antidepressant drug therapy may be indicated if depressive symptoms persist at least 2 weeks. Because of adverse effects on the heart. With lithium. or cardiovascular disease. reactions have occurred from combined therapy with an SSRI and an MAOI. which is most prominent with fluoxetine. baseline and follow-up electrocardiograms (ECGs) are recommended for all clients. including acetylcholine. anxiety. Selective Serotonin Reuptake Inhibitors (SSRIs) Selective serotonin reuptake inhibitors (SSRIs). narrow-angle glaucoma. fluoxetine should be discontinued at least 5 weeks before starting an MAOI. and the drugs should not be given concurrently or within 2 weeks of each other. release. are highly protein bound (95%). cardiac dysrhythmias. Thus. suicidal tendencies. blurred . dopamine. of which imipramine is the prototype.to 30-fold among people given identical doses. probably by competing with calcium. Sertraline (Zoloft) and citalopram (Celexa) also have active metabolites. these drugs are widely distributed in body tissues and metabolized by the liver to active and inactive metabolites. a monoamine precursor of norepinephrine. and fluvoxamine (Luvox) reach steady-state concentrations in 1 to 2 weeks. and norepinephrine. of which fluoxetine (Prozac. but fluoxetine and paroxetine (Paxil) are more likely to accumulate. SSRIs are usually given once daily. Normally. but first-pass metabolism by the liver results in blood level variations of 10. diarrhea. which may lead to accumulation with chronic administration. and seizure disorders. and reuptake of several neurotransmitters in the brain. especially in overdose. the drug may increase the activity of GABA. urinary retention). over several weeks. Paroxetine. are similar drugs that produce a high incidence of adverse effects such as sedation. Foods that interact contain tyramine. vision. TCAs are also commonly used in the treatment of neuropathic pain. Sarafem) is the prototype. tyramine is deactivated in the gastrointestinal tract and liver so that large amounts do not Tricyclic Antidepressants Tricyclic antidepressants (TCAs). urethral irritation. Adverse effects include a high incidence of gastrointestinal symptoms (eg. In this setting. However. produce fewer serious adverse effects than the TCAs. GABA. nervousness. and weight gain. impair social relationships or work performance. Amitriptyline (Elavil) is a commonly used TCA. It also stabilizes postsynaptic receptor sensitivity to neurotransmitters. steady-state blood levels are achieved slowly. For example. magnesium. excessive intake of fluids) have been ruled out. hepatic. nausea. delayed ejaculation in men and impaired orgasmic ability in women). sometimes fatal. they accumulate in the CNS and other adipose-rich tissue. anticholinergic effects (eg. mainly because they may interact with some foods and drugs to produce severe hypertension and possible heart attack or stroke. undergo extensive first-pass metabolism in the liver. and dosage ranges of individual drugs are listed in Drugs at a Glance: Antidepressant Agents. Because SSRIs are highly bound to plasma proteins. constipation. TCAs may be used in children and adolescents in the management of enuresis (bedwetting or involuntary urination resulting from a physical or psychological disorder). In addition. severe renal.

Maximum dose. give in 2 divided doses. 150 mg/d Adolescents and older adults: 30–50 mg/d. increased after several weeks if necessary. 40 mg Severe renal or hepatic impairment: Same as for older adults (continued ) . morning and noon. increased to 100 mg daily if necessary Children >6 y: Enuresis. Maintenance dose. PO 75 mg daily in 3 divided doses. Sarafem) Fluvoxamine (Luvox) Depression Obsessive-compulsive disorder Bulimia nervosa Premenstrual dysphoric disorder (Sarafem) Obsessive-compulsive disorder Paroxetine (Paxil. Maximum dose. IM 80–120 mg daily in 4 divided doses Adolescents and older adults: PO 10 mg 3 times daily and 20 mg at bedtime. 300 mg/d Children 8–17 y: PO 25 mg once daily at bedtime. Maximum dose. increase gradually if necessary PO 75 mg daily. increased to 3 mg/kg or 100 mg. 60 mg. increased to 150 mg/d if necessary. increased to 100 mg/d if necessary PO 20 mg once daily. PO 100–200 mg daily in divided doses or as a single daily dose. increased in 50-mg increments every 4–7 days if necessary. Give maintenance dose in a single dose at bedtime. Maximum dose. Maximum dose. increased up to 62. 20–50 mg/d. in divided doses or a single dose once daily PO 15–40 mg daily in 3 or 4 divided doses. 300 mg/d. morning or evening. increased to 100 mg 2 or 3 times daily by end of 1 week. starting 7 days after the last 20-mg dose Selective Serotonin Reuptake Inhibitors (SSRIs) Depression Citalopram (Celexa) Fluoxetine (Prozac.5 mg/d if necessary Elderly or debilitated adults: PO 10 mg once daily. increased to 50 mg 2 or 3 times daily by end of 1 week. maximum dose. Maximum dose 200 mg/d PO 20 mg once daily in the morning. PO 50 mg 2 or 3 times daily. 75–150 mg daily Adolescents and older adults: PO 30–40 mg daily in divided doses. usual range. in divided doses. in divided doses or a single dose at bedtime. with meals. 3 mg/kg or 200 mg. whichever is smaller. Maximum dose. Maximum dose. gradually increased to 150 mg daily if necessary. whichever is smaller. if necessary. For daily amounts above 50 mg. 250 mg daily Children and adolescents: PO 25 mg daily. in divided doses or a single dose at bedtime. 200 mg/d. increased if necessary. PO 25 mg once daily in the morning. PO 25 mg daily. Maximum dose. Pamelor) Protriptyline (Vivactil) Trimipramine maleate (Surmontil) Depression Depression Depression PO 50–100 mg once daily at bedtime. Give maintenance dose once daily. if necessary Elderly/hepatic impairment: PO 20 mg daily PO 20 mg once daily in the morning. For daily amounts above 100 mg. Paxil CR) Depression Generalized anxiety disorder Obsessive-compulsive disorder Panic disorder Social anxiety disorder PO 50 mg once daily at bedtime. increased to 100 mg daily by end of 2 weeks. Give doses larger than 20 mg once in the morning or in 2 divided doses. over 2 weeks. Give maintenance dose in a single dose at bedtime. 300 mg/d Adolescents and older adults: PO 25–100 mg daily in divided doses or as a single daily dose. increased at 1 week or longer intervals. Maximum dose. PO 90 mg once each week. gradually increased to 200 mg daily if necessary. Adolescents and older adults: PO 50 mg daily. Give maintenance dose in a single dose at bedtime. Give maintenance dose in a single dose at bedtime. increased in 25-mg increments every 4–7 days if necessary. give in 2 divided doses.CHAPTER 10 DRUGS FOR MOOD DISORDERS: ANTIDEPRESSANTS AND MOOD STABILIZERS 167 Drugs at a Glance: Antidepressant Agents Generic/Trade Name Tricyclic Antidepressants Amitriptyline (Elavil) Indications for Use Routes and Dosage Ranges Depression Amoxapine (Asendin) Depression Clomipramine (Anafranil) Obsessive-compulsive disorder Desipramine (Norpramin) Depression Doxepin (Sinequan) Imipramine (Tofranil) Depression Depression Childhood enuresis Nortriptyline (Aventyl. 60 mg/d Controlled-release tablets. 150 mg/d PO 75–150 mg daily. Adolescents and older adults: PO 5 mg 3 times daily. increased to 40 mg daily in 1 week. PO 25–50 mg 1 hour before bedtime PO 25 mg 3 or 4 times daily or in a single dose (75–100 mg) at bedtime. Older adults: PO 25 mg 2 or 3 times daily. Maximum dose. maximum daily dose 80 mg Prozac weekly (delayed-release capsules).

antidepressants (SSRIs. restlessness) that may require a sedative during the first few days of administration. increased to 150 mg twice daily (at least 8 hours apart). PO initially 37. anxiety. PO 25 mg once daily. increased after 1 week to 50 mg once daily Children: OCD. 6–12 y. Drugs that should be avoided include CNS stimulants (eg. After an oral dose. levodopa. Zyban) inhibits the reuptake of dopamine. . PO 300 mg 3 or 4 times daily to maintain a serum lithium level of 0. PO initially 75 mg/d in 2 or 3 divided doses. Acute episodes of depression usually require several months of drug therapy. increased to 60 mg/d if necessary Trazodone (Desyrel) Venlafaxine (Effexor. 25 mg once daily. OCD. in a single dose. in 2 to 4 divided doses PO 15 mg 3 times daily. PO 50 mg once daily morning or evening. The average drug half-life is about 14 hours. increased at 1-week or longer intervals to a maximum daily dose of 200 mg Panic. increased to a maximum dose of 600 mg daily if necessary Immediate release tablets. 13–17 y 50 mg once daily Monoamine Oxidase Inhibitors Isocarboxazid (Marplan) Depression Phenelzine (Nardil) Depression Tranylcypromine Depression (Parnate) Miscellaneous Antidepressants Bupropion (Wellbutrin. increase at 1-week intervals in increments of 100–200 mg/d. Dosage should be reduced with impaired hepatic or renal function. norepinephrine. Sustained release tablets. cocaine).2 mEq/L reach the systemic circulation. headache. 300–600 mg/d. adrenergics (eg. PO 100 mg twice daily. increased to 60 mg/d if necessary. pseudoephedrine). at bedtime. and meperidine. when deactivation is blocked by MAOIs. Lithobid) Bipolar disorder (mania) PO 600 mg 3 times daily or 900 mg twice daily (slow release forms) Maintenance dose. However. peak plasma levels are reached in about 2 hours. Foods that should be avoided include aged cheeses and meats. sauerkraut. Maximal single dose. Increase by 15 mg/d (at least 1–2 weeks between increments) up to 45 mg/d if necessary PO 200 mg daily in 2 divided doses. Hepatic or renal impairment: Reduce dose by 50% and increase very slowly Mood-Stabilizing Agent Lithium carbonate (Eskalith. venlafaxine). excitement. increased to 90 mg/d if necessary PO 30 mg daily in divided doses. Several metabolites are pharmacologically active. It was marketed with warnings related to seizure activity. Increase by 75 mg/d (4 days or longer between increments) up to 225 mg/d if necessary. amphetamines. PO 150 mg once daily in the morning. increased to a maximum of 300 mg daily if necessary PO 15 mg/d.6–1. Effexor XR) Depression Depression Generalized anxiety disorder (extended release only) Immediate release tablets. insomnia. usual range. and constipation. the drug has CNS stimulant effects (agitation. Miscellaneous Antidepressants Bupropion (Wellbutrin. and serotonin. Maximum single dose. Maprotiline is similar to the TCAs in therapeutic and adverse effects. tyramine is absorbed systemically and transported to adrenergic nerve terminals. Depression (Wellbutrin) Wellbutrin SR. In addition to seizures. The drug is metabolized in the liver and excreted primarily in the urine. however. Other common adverse effects include dry mouth. with food. increased motor activity. 150 mg PO 75 mg daily in single or divided doses. Bupropion is also used as a smoking cessation aid. nausea and vomiting. Elderly or debilitated adults: PO initially 100 mg/d in 2 divided doses PO 100–300 mg daily. concentrated yeast extracts. PTSD. increased to 100 mg 3 times daily (at least 6 h apart) if necessary. Seizures are most likely to occur with doses above 450 mg/day and in clients known to have a seizure disorder.5 or 75 mg/d in a single dose morning or evening. Increase by 75 mg/d (4 days or longer between increments) up to 225 mg/d if necessary.168 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Drugs at a Glance: Antidepressant Agents (continued ) Generic/Trade Name Sertraline (Zoloft) Indications for Use Depression Obsessive-compulsive disorder (OCD) Panic disorder Post-traumatic stress disorder (PTSD) Routes and Dosage Ranges Depression. Extended release capsules. Zyban) Smoking cessation (Zyban) Maprotiline Mirtazapine (Remeron) Nefazodone (Serzone) Depression Depression Depression PO 10 mg twice daily. 150 mg. Bupropion has few adverse effects on cardiac function and does not cause orthostatic hypotension or sexual dysfunction. buspirone. and fava beans. These effects may increase the risk of abuse. where it causes a sudden release of large amounts of norepinephrine.

if a client on an MAOI is to be transferred to venlafaxine. Consequently. It has a long half-life (2 to 3 days) and crosses the placenta. lithium diuresis) and may lower serum lithium levels to nontherapeutic ranges. aspartate and alanine aminotransferases [AST and ALT]) should be measured before starting nefazodone therapy. lamotrigine. alcohol or benzodiazepine antianxiety or hypnotic agents) because of additive sedation. electroconvulsive therapy. because they modify nerve cell function. and women should use effective birth control methods while taking this drug. vasodilation). Adverse effects include CNS (anxiety. Nefazodone (Serzone) inhibits the neuronal reuptake of serotonin and norepinephrine. but none are FDA-approved for this purpose. and lactation. Mirtazapine should not be taken concurrently with other CNS depressants (eg. It is metabolized by the liver and excreted primarily by the kidneys. with peak serum levels in 1 to 3 hours after a dose and steadystate concentrations in 5 to 7 days. The drug is well absorbed after oral administration. cardiac dysrhythmias. Serum lithium concentrations should be monitored frequently because they vary widely among clients taking similar doses and because of the narrow range between therapeutic and toxic levels. Newer drugs (eg. Mood-Stabilizing Agents Lithium carbonate (Eskalith) is a naturally occurring metallic salt that is used in bipolar disorder. hypomania. hepatic cirrhosis. insomnia. serum levels of liver enzymes (eg. It is contraindicated in pregnancy and liver damage and should be used with caution in people with cardiovascular or cerebrovascular disorders. GI (anorexia. The drug crosses the placenta and may enter breast milk. debilitation. Nefazodone should not be taken with an MAOI because of the risk of severe toxic effects. baseline studies of renal. dehydration. It is well absorbed after oral administration. and constipation. dizziness. The amount of reabsorption depends on the concentration of sodium in the proximal renal tubules. suicidal ideation. In addition. rash. constipation. pruritus) symptoms. and peak plasma concentrations are obtained within 30 minutes to 2 hours. vomiting. urine. periodically during therapy. cardiac. somnolence. including agitation. nausea. dark urine) develop. It is metabolized in the liver. It is metabolized in the liver and produces two active metabolites. serotonin receptors. impotence. dizziness. increased appetite. mainly to inactive metabolites. Before lithium therapy is begun. nausea. tachycardia. insomnia. Common adverse effects include drowsiness (with accompanying cognitive and motor impairment). It is contraindicated during pregnancy. serotonin. agitation. It does not cause sexual dysfunction. and feces. if a client on an MAOI is to be transferred to nefazodone. it should not be taken concurrently with an MAOI or for 14 days after stopping an MAOI. sedation. . the MAOI should be discontinued at least 14 days before starting nefazodone. dreams. Venlafaxine does not interact with drugs metabolized by the cytochrome P450 system. GI symptoms (nausea. such as bupropion. Approximately 80% of a lithium dose is reabsorbed in the proximal renal tubules. vomiting. and priapism (prolonged and painful penile erection). It is excreted in breast milk. so adequate renal function is a prerequisite for lithium therapy. and thyroid status should be obtained because adverse drug effects involve these organ systems. edema. topiramate. and dermatologic (sweating. Anticonvulsants (see Chap. but it should not be taken concurrently with MAOIs because of increased serum levels and risks of toxicity. Venlafaxine (Effexor) inhibits the reuptake of norepinephrine. dry mouth. nervousness. confusion. Thus far. Carbamazepine (Tegretol) and valproate (Depakene) are commonly used. most of the drugs seem to have some beneficial effects but additional studies are needed. An MAOI should not be started until at least 14 days after stopping mirtazapine. excessive sodium intake causes more lithium to be excreted (ie. It is metabolized in the liver and excreted in urine. genitourinary (abnormal ejaculation. Because of its association with liver failure. hypovolemia. thereby increasing the activity of these neurotransmitters in the brain. It is often given concurrently with a stimulating antidepressant. thereby increasing the amount of these neurotransmitters in the brain. sertraline. the nefazodone should be discontinued at least 7 days before starting the MAOI. Trazodone is well absorbed with oral administration. diarrhea). the drug decreases anxiety. dizziness. the MAOI should be discontinued at least 14 days before starting venlafaxine. Adverse effects resemble those of SSRIs and TCAs. oxcarbazepine) are being used and studied regarding their effects in bipolar disorder. and migraine headache as well as depression. diarrhea). Trazodone (Desyrel) is used more often for sedation and sleep than for depression because high doses (>300 mg/day) are required for antidepressant effects and these amounts cause excessive sedation for many clients. dizziness. orthostatic hypotension. gabapentin. and histamine H1 receptors.CHAPTER 10 DRUGS FOR MOOD DISORDERS: ANTIDEPRESSANTS AND MOOD STABILIZERS 169 Mirtazapine (Remeron) blocks presynaptic alpha2adrenergic receptors (which increases the release of norepinephrine). Baseline electrolyte studies are also necessary. fluoxetine. anorexia. urinary frequency). which are inhibited by nefazodone. Other potentially serious drug interactions include increased CNS depression with general anesthetics and decreased metabolism of drugs metabolized by the cytochrome P450 3A4 enzymes. or venlafaxine. tremors). Adverse effects include sedation. insomnia. weight gain. Lithium is not metabolized by the body. it is entirely excreted by the kidneys. A deficiency of sodium causes more lithium to be reabsorbed and increases the risk of lithium toxicity. and immediately when symptoms of liver dysfunction (eg. and peak plasma levels occur within 2 hours after an oral dose. mainly to treat and prevent manic episodes. If a client on nefazodone is to be transferred to an MAOI. and dopamine. the venlafaxine should be discontinued at least 7 days before starting the MAOI. vomiting. mania. and skin rash. 11) are also used as mood stabilizing agents in bipolar disorder. cardiovascular (hypertension. If a client on venlafaxine is to be transferred to an MAOI. headache.

Interventions Use measures to prevent or decrease the severity of depression. to avoid taking antidepressant drugs. St. Depression also occurs without an identifiable cause. and work status. and social interactions when unable to provide self-care • Resume self-care and other usual activities • Avoid preventable adverse drug effects Nursing Process Assessment Assess the client’s condition in relation to depressive disorders. opioid analgesics. • Be cared for by staff in areas of nutrition. • Identify the client’s usual coping mechanisms for stressful situations. and increasing or decreasing socialization. whereas another may find increased contact desirable. possibly severe. hygiene. antidepressant drugs (eg. SSRIs. Most authorities agree that there is insufficient evidence to support the use of St. and method for carrying out the plan. and so forth) • Self Care Deficit related to fatigue and self-esteem dis• • • • turbance with depression or sedation with antidepressant drugs Sleep Pattern Disturbance related to mood disorder or drug therapy Risk for Injury related to adverse drug effects Risk for Violence: Self-Directed or Directed at Others Deficient Knowledge: Effects and appropriate use of antidepressant and mood stabilizing drugs Planning/Goals The client will: • Experience improvement of mood and depressive state • Receive or self-administer the drugs correctly • Be kept safe while sedated during therapy with the TCAs and related drugs • Be assessed regularly for suicidal tendencies. and behavior that may be helpful to one client may not be helpful to another. John’s wort. exercise. teach them to purchase products from reputable sources because the amount and type of herbal content may vary among manufacturers. Clinical Herbal Supplement St. Coping mechanisms vary widely. John’s wort for mild to moderate depression and that more studies are needed in order to confirm the herb’s safety and effectiveness. ability to perform usual tasks. with fewer adverse effects than antidepressant drugs. Specific measures include the following: • Support the client’s usual mechanisms for handling stressful situations. These symptoms are relieved by stopping the herb. impaired interpersonal relationships. A 3-year. allow him or her to participate in setting goals and making . both consumers and health care professionals seem to underestimate the risks of taking this herbal supplement. General measures include supportive psychotherapy and reduction of environmental stress. Areas to assess include health status. place the client at high risk for suicide. ability. Antidepressant effects are attributed mainly to hypericin. Most of the previous studies were considered flawed. nausea. although several other active components have also been identified. John’s wort (Hypericum perforatum) is an herb that is widely self-prescribed for depression. MAOIs. accompanied by the intent. Several studies. scheduling rest periods. Severe or prolonged illness. multicenter study by the National Institutes of Health concluded that the herb is not effective in major depression.170 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM • Observe for signs and symptoms of depression. For example. indicate its usefulness in mild to moderate depression. caretakers will implement safety measures. If present. most of which used about 900 mg daily of a standardized extract. All of these interactions may result in hypertension. and job dissatisfaction may precipitate depression. try to determine their frequency. fatigue. GI distress. fatigue and insomnia may be caused by a variety of disorders and range from mild to severe. For clients who report use of St. dry mouth. and sleep disturbances. When symptoms are present. and severity. alcohol. dizziness. which are usually infrequent and mild. because effects are unknown. • Identify clients at risk for current or potential depression. duration. bronchodilators. For example.” Adverse effects. one person may prefer being alone or having decreased contact with family and friends. John’s wort as “natural Prozac. to avoid the herb during pregnancy. include constipation. job. Drug interactions may be extensive. Helpful actions may involve relieving pain or insomnia. skin rash. Overall. John’s wort. TCAs). significant other. assess for suicidal thoughts and behaviors. Statements indicating a detailed plan. or amino acid supplements containing phenylalanine and tyrosine. Nursing Diagnoses • Dysfunctional Grieving related to loss (of health. family and social relationships. nasal decongestants or other overthe-counter cold and flu medications. • Call the client by name. photosensitivity. • When a client appears depressed or has a history of depression. John’s wort should not be combined with alcohol. and to use sunscreen lotions and clothing to protect themselves from sun exposure. inability to work. when feasible. and cold and flu medications while taking St. but the herb is thought to act similarly to antidepressant drugs. Some herbalists refer to St. The mechanism of action is unknown. encourage self-care activities. restlessness. manifestations are nonspecific and vary in severity.

When used prophylactically. The response of family members to individual drugs may be significant because there is a strong genetic component to depression and drug response. However. 7. With SSRIs. smaller doses may be indicated in older adults and clients taking multiple medications. Evaluation • Observe for behaviors indicating lessened depression. if any. MAOIs. Mirtazapine decreases anxiety. Antidepressant drug therapy is usually initiated with small. 4. For example. and causes sexual dysfunction. they may be more cost effective overall because TCAs are more likely to cause serious adverse effects. they require monitoring of plasma drug levels and ECGs. Nefazodone has sedating and anxiolytic properties that may be useful for clients with severe insomnia. • Observe and interview regarding adverse drug effects. may be as effective as lithium as a mood-stabilizing agent. bupropion. nefazodone. . For clients hospitalized on medical-surgical units. it has been associated with liver failure and probably should not be given to clients with significant liver impairment. previous history of drug response. SSRIs. and removal of potential weapons from the environment. bupropion. an SSRI or another newer drug is preferred over a TCA because the TCAs are much more toxic in overdoses. Guidelines for choosing one SSRI over another have not been established.CHAPTER 10 DRUGS FOR MOOD DISORDERS: ANTIDEPRESSANTS AND MOOD STABILIZERS 171 decisions. Dosage and Administration Dosage of antidepressant drugs should be individualized according to clinical response. anxiety. and desipramine are less likely to cause seizures. the TCA probably should be discontinued or changed. although it is not FDA approved for that purpose. For a potentially suicidal client. that is probably the drug of choice for repeated episodes of depression. it does not cause sexual dysfunction or clinically significant drug–drug interactions. and insomnia. It is often used in clients who do not respond to lithium. 8. In addition. agitation. With TCAs. medical conditions. Criteria for choosing bupropion. Venlafaxine and MAOIs can increase blood pressure. if a client (or a close family member) responded well to a particular drug in the past. the drug decreases the frequency and intensity of manic cycles. and the specific drug’s adverse effects. transfer to a psychiatric unit may be needed. increases blood pressure. mirtazapine. These drugs are effective and usually produce fewer and milder adverse effects than other drugs. The newer drugs are much more expensive than the TCAs. Institute suicide precautions for clients at risk. Specific guidelines for dosage include the following: 1. initial selection may be based on the client’s previous response or susceptibility to adverse effects. clomipramine. and venlafaxine. For clients with seizure disorders. and venlafaxine are not clearly defined. As with most other drugs. as well as depression. initiate treatment before depression becomes severe. These actions promote a positive self-image. divided doses that are gradually increased until therapeutic or adverse effects occur. Venlafaxine has stimulant effects. Lithium is the drug of choice for clients with bipolar disorder. most antidepressants can cause hypotension. migraines. MAOIs are third-line drugs for the treatment of depression because of their potential interactions with other drugs and certain foods. 6. and agitation. but does not cause significant drug–drug interactions For clients with cardiovascular disorders. and the drug inhibits cytochrome P450 3A4 enzymes that metabolize many drugs. If therapeutic effects do not occur within 4 weeks. SSRIs may have a hypoglycemic effect and bupropion and venlafaxine have little effect on blood sugar levels. Additional guidelines for choosing a drug include the following: 1. 3. 2. and venlafaxine are rarely associated with cardiac dysrhythmias. other antidepressant drugs or when electroconvulsive therapy is refused or contraindicated. • Observe and interview regarding suicidal thoughts and behaviors. but the SSRIs. serum nefazodone levels are increased in clients with cirrhosis. an anticonvulsant. the choice of an antidepressant depends on the client’s age. PRINCIPLES OF THERAPY Drug Selection Because the available drugs seem similarly effective. • When signs and symptoms of depression are observed. because some clients tolerate or respond better to one TCA than to another. lithium is effective in controlling mania in 65% to 80% of clients. Carbamazepine (Tegretol). When used therapeutically. often on a one-to-one basis. Bupropion does not cause orthostatic hypotension or sexual dysfunction. However. and clients are more likely to stop taking them. The SSRIs are the drugs of first choice. An MAOI is most likely to be prescribed when the client does not respond to 5. Cost also needs to be considered. In addition. an optimal response may require 300 mg to 500 mg daily. nefazodone. Dosage may be increased after 3 or 4 weeks if depression is not relieved. With nefazodone. • Interview regarding feelings and mood. and praise efforts to accomplish tasks. nefazodone. therapy is begun with once-daily oral administration of the manufacturer’s recommended dosage. For clients with diabetes mellitus. These usually involve close observation. and maprotiline should be avoided.

with potentially serious consequences. These drugs are often taken twice daily. surgeon. ✔ With bupropion. These are potentially serious adverse drug effects. ✔ Bupropion is a unique drug prescribed for depression (brand name. Decreased salt intake (eg. or other aspects may be changed to solve the problem and allow continued use of the medication. ✔ Avoid activities that require alertness and physical coordination (eg. ✔ Therapeutic effects (relief of symptoms) may not occur for 2 to 4 weeks after drug therapy is started. 4. lithium therapy may be lifelong. dizziness. ✔ Avoid alcohol and other central nervous system depressants (eg. Potentially serious adverse effects or drug interactions may occur if certain other drugs are prescribed. and low blood pressure may occur. ✔ Learn the name and type of a prescribed antidepressant drug to help avoid undesirable interactions with other drugs or a physician prescribing other drugs with similar effects. fainting. seizures. any drugs that cause drowsiness). take at bedtime to aid sleep and decrease side effects. low-salt diet) increases risk of adverse effects from lithium. and mental confusion. support groups. several precautions are needed for safe use: 1. Take with food or milk or soon after a meal to decrease stomach upset. Celexa. ✔ With a tricyclic antidepressant (eg. When used for smoking cessation. amitriptyline). Notify a health care provider if a skin rash or other allergic reaction occurs. Drink 8 to 12 glasses of fluids daily. Also. 6. stop taking lithium and contact the prescribing physician or other health care provider. Increased intake may decrease therapeutic effects. irregular heartbeat. There are several different types of antidepressant drugs. as prescribed. ✔ Counseling. Paxil. 3. Overdoses may cause seizures. ✔ Do not take other prescription or over-the-counter drugs without consulting a health care provider. and other nonmedication treatments are recommended along with drug therapy. Potentially serious drug interactions may occur. and do not take the morning dose of lithium until the blood sample has been obtained. If signs of overdose occur (eg. avoid excessive intake of caffeine-containing beverages. with different characteristics and precautions for safe and effective usage. notify a health care provider if a skin rash or other allergic reaction occurs. Zoloft). Accurate measurement of serum drug levels requires that blood be drawn approximately 12 hours after the previous dose of lithium. Self-administration ✔ With a selective serotonin reuptake inhibitor (eg. operating other machinery) until reasonably sure the medication does not make you drowsy or impair your ability to perform the activities safely. In addition. difficulty breathing. the dose. perhaps years. Regular measurements of blood lithium levels are necessary for safe and effective lithium therapy. including overthe-counter cold remedies. Do not alter doses when symptoms subside. unsteady walking. the type of drug. 5. tremor. as well as other adverse effects. take in the morning because the drug may interfere with sleep if taken at bedtime. it is very important not to think the drug is ineffective and stop taking it prematurely. . It is extremely important not to increase the dose or take the two brand names at the same time (as might happen with different physicians or filling prescriptions at different pharmacies). Prozac. driving a car. Do not alter dietary salt intake. drowsiness. Antidepressants are usually given for several months. John’s wort while taking a prescription antidepressant drug. muscle weakness). ✔ With lithium. Loss of salt in sweat increases the risk of adverse effects from lithium. Zyban is recommended for up to 12 weeks if progress is being made. it is considered unlikely that longer drug use will be helpful. ✔ Do not take the herbal supplement St. An allergic reaction may require that the drug be discontinued. Zyban). dentist or nurse practitioner about the antidepressant drugs being taken. take as directed or ask for instructions. restlessness. relaxation techniques. ✔ Inform any physician. Minimize activities that cause excessive perspiration. 2. Wellbutrin) and for smoking cessation (brand name. ✔ With nefazodone (Serzone) and venlafaxine (Effexor). If significant progress is not made by approximately 7 weeks. If a problem occurs. ✔ Do not stop taking any antidepressant drug without discussing it with a health care provider. diarrhea. Allergic reactions are uncommon but may require that the drug be discontinued. Serious interactions may occur. Report for measurements of lithium blood levels as instructed. Excessive drowsiness.172 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM CLIENT TEACHING GUIDELINES Antidepressants and Lithium General Considerations ✔ Take antidepressants as directed to maximize therapeutic benefits and minimize adverse effects. take two or three times daily. As a result. Caffeine has a diuretic effect and dehydration increases lithium toxicity. vomiting. report urinary retention.

Inhibition of 1A2 enzymes slows metabolism of acetaminophen. serum drug levels and risks of adverse effects are greatly increased. clozapine. erythromycin.5 mEq/L because the risk of serious toxicity is increased at higher levels. With lithium. Give the drug in equally divided doses. which are increased to the desired dose over 1 to 2 weeks. • Fluoxetine. tricyclic antidepressants. Specific interactions include the following: • Fluvoxamine inhibits both 1A2 and 3A4 enzymes.CHAPTER 10 DRUGS FOR MOOD DISORDERS: ANTIDEPRESSANTS AND MOOD STABILIZERS 173 Nursing Notes: Apply Your Knowledge Ms. lithium doses should be lowered. the maximal daily dose for immediate-release tablets (sustained-release. Some authorities recommend 9 months of treatment after symptoms subside for a first episode of depression. Serum lithium levels should be measured at least every 3 months during long-term maintenance therapy. Lower doses are indicated for older adults and for clients with conditions that impair lithium excretion (eg. With bupropion. The recommended initial dose is 200 mg. the serum drug concentration should be measured two or three times weekly in the morning. control of symptoms. 0.2 mEq/L (SI units. tacrine. three times daily (at least 6 hours apart). 2. therapy is begun with small doses. midazolam. followed by gradual tapering of the dose and drug discontinuation.2 mmol/L). With the use of TCAs for acute depression. long-term therapy is the usual practice because of a high recurrence rate if the drug is discontinued. large total doses. 12 hours after the last dose of lithium. 400 mg). Minimal effective doses are approximately 150 mg/day of imipramine (Tofranil) or its equivalent. tamoxifen. Effects of Antidepressants on Other Drugs The SSRIs are strong inhibitors of the cytochrome P450 enzyme system. Inhibition of 3A4 enzymes slows metabolism of benzodiazepines (alprazolam. 2D6. Serum levels are required because therapeutic doses are only slightly lower than toxic doses and because clients vary widely in rates of lithium absorption and excretion. 200 mg). Inhibiting the enzymes that normally metabolize or inactivate a drug produces the same effect as an excessive dose of the inhibited drug. the therapeutic range of serum levels is 0. c. nifedipine. codeine. When she returns to the clinic. recent studies indicate that full therapeutic doses (if clients can tolerate the adverse effects) for up to 5 years are effective in preventing recurrent episodes. As a result. caffeine. gradually tapering the dose over 2 to 4 weeks delays recurrence of symptoms. and long-term therapy after a third episode. Recommendations to avoid these risk factors are: a. Duration of Drug Therapy Guidelines for the duration of antidepressant drug therapy are not well established. a dose that is therapeutic in one client may be toxic in another. Jordan? Once symptoms of mania are controlled. 5 years after symptoms subside for a second episode.5 to 1. and large or abrupt increases in dosage. The maximal single dose of immediate-release tablets is 150 mg (sustained-release. . Elderly clients may experience fewer adverse reactions if divided doses are continued. She also complains that she is having trouble sleeping. ritonavir. 3. and zolpidem. cyclosporine. and warfarin. verapamil). Once dosage is established. TCAs are often given once daily at bedtime. haloperidol. calcium channel blockers (diltiazem. gradually increased to 300 mg. The long-term effects of SSRIs and newer agents have not been studied. protease inhibitors (antiAIDS drugs. which metabolizes many drugs. saquinavir). d. With TCAs. and sertraline inhibit 2D6 enzymes and slow metabolism of bupropion. paroxetine. and there are differences of opinion. Jordan started taking fluoxetine (Prozac) for depression 1 week ago. diuretic drug therapy. With TCAs. olanzapine. especially those metabolized by the 1A2. What teaching is appropriate for Ms. renal impairment. TCAs can be administered once or twice daily because they have long elimination half-lives. dosage may be increased to 450 mg.5 to 1. Maintenance therapy for depression requires close supervision and periodic reassessment of the client’s condition and response. twice daily for sustained-release tablets. dosage should be based on serum lithium levels. When lithium therapy is being initiated. Thus. low doses have been given for several months. theophylline. For most clients. and 3A4 groups of enzymes. steroids. seizures are more likely to occur with large single doses. most often because of adverse effects or the client’s lack of adherence to the prescribed regimen. With lithium. triazolam). This regimen is effective and well tolerated by most clients. However. and successive episodes often are more severe and more difficult to treat. warfarin. for immediate-release tablets. indinavir. Serum lithium levels should not exceed 1. The recommended maintenance dose is the lowest amount that maintains remission. 4. and occurrence of adverse effects. b. decreased cardiac output). plasma levels are helpful in adjusting dosages. she states she is still depressed and requests that the dosage of Prozac be increased. If no clinical improvement occurs after several weeks of 300 mg/day. When lithium is discontinued. One argument for long-term maintenance therapy is that depression tends to relapse or recur. low-salt diet. dehydration.

Lithium overdose: Toxic manifestations occur with serum lithium levels above 2. nausea and vomiting. Management includes symptomatic and supportive treatment. Nefazodone or venlafaxine overdose: Symptoms include increased incidence or severity of adverse effects. flecainide. restlessness. and drowsiness most often reported. carbamazepine. dysrhythmias. coma. tremors. sweating. Paroxetine. Symptoms . performing continuous ECG monitoring of comatose clients or those with respiratory insufficiency or wide QRS intervals. hypotension. respiratory. seizures. oliguria. propranolol. metoprolol. but few studies have been done and effects are unknown. In general. Fluoxetine has a long half-life and has not been associated with withdrawal symptoms. and death. giving intravenous fluids and vasopressors for severe hypotension. tremors. nortriptyline.174 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM desipramine. treatment is symptomatic and supportive. risperidone. The most clearly defined withdrawal syndromes are associated with SSRIs and TCAs. hemodialysis is preferred because it removes lithium from the body. symptoms occur more rapidly and may be more intense with drugs having a short half-life. decreasing absorption (eg. and instituting treatment if indicated. MAOI overdose: Symptoms occur 12 hours or more after drug ingestion and consist primarily of adrenergic ef- fects (eg. an intravenous benzodiazepine (eg. and seizures. and timolol. hypomania. the occurrence of withdrawal symptoms may indicate that the client has omitted doses or stopped taking the drug. may be associated with relatively severe withdrawal symptoms even when discontinued gradually. 5 to 7 days) to clients with suicidal tendencies and storing the drugs in places inaccessible to young children. heart block. agitation. and headache and last from several days to several weeks. Lower-than-usual doses of both the TCA and the other drug may be needed. and circulatory failure. convulsions. Management consists of diuresis. tachycardia. dosage of the benzodiazepine should be reduced by 50% or more. confusion. establishing and maintaining a patent airway. hypomania. above). Management of TCA toxicity consists of performing gastric lavage and giving activated charcoal to reduce drug absorption. and giving intravenous phenytoin (Dilantin) or fosphenytoin (Cerebyx) or a parenteral benzodiazepine (eg. Specific measures include the following: SSRI overdose: Symptoms include nausea. visual or tactile hallucinations. General measures to treat acute poisoning include early detection of signs and symptoms. Bupropion overdose: Symptoms include agitation and other mental status changes. convulsive seizures. General treatment measures include hospitalization. There are no specific antidotes. vomiting. dextromethorphan. impaired consciousness.5 mEq/L and include nystagmus. and supporting vital functions. With SSRIs. coma). Prevention and Management of Withdrawal Symptoms Withdrawal symptoms have been reported with sudden discontinuation of most antidepressant drugs. these drugs should be tapered in dosage and discontinued gradually unless severe drug toxicity. With severe overdoses. choreiform movements. which has a half-life of approximately 24 hours and does not produce active metabolites. Treatment involves supportive care to maintain vital functions. lorazepam) is the drug of first choice. hypotension. For a client on maintenance drug therapy. delirium. • Nefazodone also inhibits 3A4 enzymes and slows the metabolism of many drugs (see fluvoxamine. tremor. phenothiazines. with nausea. Toxicity is most likely to occur in depressed clients who intentionally ingest large amounts of drug in suicide attempts and in young children who accidentally gain access to medication containers. nausea. increased rate of respiration. More serious symptoms may include aggression. agitation. and suicidal tendencies. As with other psychotropic drugs. including correction of fluid and electrolyte imbalances. withdrawal symptoms include dizziness. over 7 to 10 days. If nefazodone is given with alprazolam or triazolam (benzodiazepines). myocardial depression). and other signs of CNS stimulation. TCA overdose: Symptoms occur 1 to 4 hours after drug ingestion and consist primarily of CNS depression and cardiovascular effects (eg. giving activated charcoal to conscious clients). Toxicity of Antidepressants and Lithium: Recognition and Management Some antidepressant drugs are highly toxic and potentially lethal when taken in large doses. Most antidepressants may be tapered and discontinued over approximately 1 week without serious withdrawal symptoms. Measures to prevent acute poisoning from drug overdose include dispensing only a few days’ supply (ie. or other life-threatening conditions are present. such as maintaining an adequate airway and ventilation and administering activated charcoal. mood disturbances. restlessness. propafenone). phenothiazines. anaphylactic reactions. Other SSRIs have short half-lives and may cause withdrawal reactions if stopped abruptly. or hemodialysis to remove the drug from the body. If seizures occur. • Mirtazapine and venlafaxine are not thought to have clinically significant effects on cytochrome P450 enzymes. stopping the drug. acidification of urine. seizures and diastolic hypertension with venlafaxine. flecainide. Death usually results from cardiac. Hypotension and excessive sedation may occur with nefazodone. • TCAs are metabolized by 2D6 enzymes and may inhibit the metabolism of other drugs metabolized by the 2D6 group (other antidepressants. vomiting. nystagmus. lorazepam) if seizures occur.

hypersalivation. In addition. these drugs can cause symptoms of excessive cholinergic activity (ie. Considerations include the following: 1. The shortacting SSRIs should be tapered in dosage and gradually discontinued to prevent or minimize withdrawal reactions. It is usually recommended that antidepressants be tapered in dosage and gradually discontinued. Although all ethnic groups are genetically heterogeneous and individual members may respond differently. Lithium should be stopped 1 to 2 days before surgery and resumed when full oral intake of food and fluids is allowed. For adolescents. Studies have not been done with newer antidepressants. However. Most studies have been done with TCAs and a limited number of Asian subgroups. if at all. anorgasmia. Thus. are approved for treatment of obsessive-compulsive disorder. and some TCAs are approved for treatment of enuresis). Lithium may prolong the effects of anesthetics and neuromuscular blocking drugs. especially with high doses. with some re- Use in Children Depression commonly occurs in children and adolescents and antidepressant drugs are widely prescribed. You do so. experience a higher incidence of adverse effects. several studies document differences in drug effects in nonwhite populations. the longterm effects of antidepressant drugs on the developing brain are unknown. urinary urgency. 1. 2. With lithium. Few studies have been done. Hispanics’ responses to antidepressant drugs are largely unknown. dizziness. . TCAs should be discontinued several days before elective surgery and resumed several days after surgery. Genetic or Ethnic Considerations Antidepressant drug therapy for nonwhite populations in the United States is based primarily on dosage recommendations. Although some antidepressants are approved for other uses in children (eg. However. the main concern is over those with strong anticholinergic effects. To decrease adverse effects. health care providers need to consider potential differences in responses to drug therapy. perioperatively because of the risk of serious adverse effects and adverse interactions with anesthetics and other commonly used drugs. SSRIs and miscellaneous antidepressants have not been studied in relation to perioperative use. was admitted to your psychiatric unit after a suicide attempt.CHAPTER 10 DRUGS FOR MOOD DISORDERS: ANTIDEPRESSANTS AND MOOD STABILIZERS 175 may include a flu-like syndrome with nausea. headache. respond more rapidly. A recommended rate for tapering TCAs is approximately 25 to 50 mg every 2 to 3 days. Moreover. fatigue. muscle aches. The differences are mainly attributed to genetic or ethnic variations in drugmetabolizing enzymes in the liver. diarrhea. and insomnia. When you approach her with her morning medications (including an antidepressant). Overall. fluvoxamine and sertraline. however. and sweating). drug therapy is largely empiric and of unproven effectiveness. African Americans report more adverse reactions than whites and may need smaller doses. porting a need for lower doses of TCAs and greater susceptibility to anticholinergic effects. Use in Perioperative Periods Antidepressants must be used very cautiously. Studies have not been done with newer antidepressants. two SSRIs. initial doses may need to be lower than those given to whites and later doses should be titrated according to clinical response and serum drug levels. This recommendation is supported by a survey from several Asian countries that reported the use of much smaller doses of TCAs than in the United States. and chart the medications. abdominal cramping. MAOIs are contraindicated and should be discontinued at least 10 days before elective surgery. it is probably best to reserve drug therapy for those who do not respond to nonpharmacologic treatment and those whose depression is persistent or severe enough to impair function in usual activities of daily living. With lithium. When stopped abruptly. pharmacokinetic data. she is lying on her bed in a fetal position. 3. She instructs you to just leave her medications on the table so she can take them later. it may be important to discuss sexual effects because the SSRIs and venlafaxine cause a high incidence of sexual dysfunction (eg. With TCAs. in Asians as in African Americans. and adverse effects derived from white recipients. African Americans tend to have higher plasma levels for a given dose. vomiting. there are no apparent differences between effects in Asians and whites. Asians tend to metabolize antidepressant drugs slowly and therefore have higher plasma drug levels for a given dose than whites. baseline and periodic ECGs are recommended to detect adverse drug effects on the heart. In addition. none is approved for treatment of depression. For most children and adolescents. it seems reasonable to discontinue the drugs when feasible because of potential adverse effects. How Can You Avoid This Medication Error? Jane. baseline and periodic ECGs are recommended to detect adverse drug effects on the heart. and metabolize TCAs more slowly than whites. there are few reliable data or guidelines for the use of antidepressants in children and adolescents. To avoid drug toxicity. it cannot be assumed that all antidepressant drugs and all people of Asian heritage respond the same. whereas others report no differences between Hispanics and whites. 2. initial doses should be approximately half the usual doses given to whites and later doses should be titrated according to clinical response and serum drug levels. She opens her eyes when you call her name. especially on the cardiovascular system and CNS. leave the room. a 17-year-old.

Because of potentially serious adverse effects. nortriptyline or desipramine is preferred. Although their effects in older adults are not well delineated. from 7 to 9 days to 12 days. Initial and maintenance doses should be small because the drugs are metabolized and excreted more slowly than in younger adults. hypotension. However. mainly amitriptyline. but it has been used to treat bipolar disorder and aggressiveness. Bupropion. and no residual benefits continue once the drug is stopped. 6. the dose must be markedly reduced and plasma lithium levels must be closely monitored. If a TCA is chosen for an older adult. renal. blood pressure. The drugs should be used cautiously in clients with severe liver impairment. serum drug levels. The weight loss often associated with . longer intervals between doses. If given to a client with renal impairment or unstable renal function. These drugs produce similar adverse effects in older adults as in younger adults. However. There is evidence that children metabolize TCAs faster than adults. ECGs. with resultant higher plasma levels. initial doses should be low and increased gradually. and their safety and effectiveness have not been established. With lithium. 5. Use in Hepatic Impairment Hepatic impairment leads to reduced first-pass metabolism of most antidepressant drugs. to achieve therapeutic effects. increased GI motility. In addition. and ECGs should be monitored regularly. and less frequent dosing are indicated. restlessness). and that of norfluoxetine. When a TCA is used for enuresis. and sedation. and psychomotor adverse effects than the TCAs and related antidepressants. for children. they are used to treat depression. but severe impairment may increase plasma levels and adverse effects of virtually all antidepressants. hypomania. urinary retention. slow increases. cardiac conduction abnormalities. Use in Older Adults SSRIs are the drugs of choice in older adults as in younger ones because they produce fewer sedative. Clearance of sertraline is also decreased in clients with cirrhosis. anticholinergic. and nortriptyline. 4. Nefazodone and venlafaxine may also be used in older adults. and sleep disorders. Lithium is not approved for use in children younger than 12 years of age. imipramine. the average half-life of fluoxetine may increase from 2 to 3 days to more than 7 days. In clients with cirrhosis. effectiveness may decrease over time. and plasma drug levels should be monitored. erectile dysfunction). and venlafaxine in children younger than 18 years of age. and nefazodone are unlikely to cause sexual dysfunction. Initial dosage should be decreased by 30% to 50% to avoid serious adverse reactions. Safety and effectiveness have not been established for amoxapine and MAOIs in children younger than 16 years of age or for bupropion.176 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM 3. In addition. As with adults. TCAs may cause or aggravate conditions that are common in older adults (eg. Vital signs. headache) are more common in children than in adults. the active metabolite. desipramine. according to regular measurements of serum drug levels. narrow-angle glaucoma). Thus. confusion. Common adverse effects include sedation and activation. and hepatic functions are often diminished. and slower dose increases than usual. Paroxetine has a short half-life and no active metabolites. Lithium is eliminated only by the kidneys and it has a very narrow therapeutic range. Mild or moderate impairment has few effects. mirtazapine. MAOIs may be more likely to cause hypertensive crises in older adults because cardiovascular. Use in Renal Impairment Antidepressants should be used cautiously in the presence of severe renal impairment. Common adverse effects include sedation. Divided doses may be better tolerated and minimize withdrawal symptoms. and withdrawal symptoms (eg. increments should be small. TCAs are not recommended for use in children younger than 12 years of age except for short-term treatment of enuresis in children older than 6 years of age. Cautious use means lower doses. SSRIs may be undesirable in older adults. increased energy and motivation) from the adverse effects of behavioral activation (agitation. small initial doses. with smaller initial doses and increments recommended. nefazodone. mirtazapine. cardiotoxic. SSRIs are not approved in children (<18 years of age). as for other groups. and smaller or less frequent doses may be prudent. SSRIs may be eliminated more slowly. Children normally excrete lithium more rapidly than adults. Fluoxetine and sertraline are less readily metabolized to their active metabolites with hepatic impairment. for example. any TCA should be given in small doses initially and gradually increased over several weeks. these drugs are considered first-line antidepressants and safer than TCAs and MAOIs. fatigue. A TCA probably is not a drug of first choice for adolescents because TCAs are more toxic in overdose than other antidepressants and suicide is a leading cause of death in adolescents. nervousness. if necessary. decreased libido. it is often difficult to distinguish therapeutic effects (improvement of mood. malaise. but increased plasma levels can occur with severe hepatic impairment. initial doses should be relatively low and gradually increased according to regular measurements of serum drug levels. impaired compensatory mechanisms make older adults more likely to experience anticholinergic effects.

The main role of the nurse may be in recognizing depressive states and referring clients for treatment. 0. give immediately after mixing. 8) c. If an antidepressant medication was recently started. and interest in surroundings. observe for decreased symptoms of the disorders (see Chap. b. citalopram and sertraline may be given morning or evening. potential adverse drug effects. With lithium. he or she must be vigilant for signs and symptoms of major depression. increased appetite. Home Care Whatever the primary problem for which a home care nurse is visiting a client. its use must be NURSING ACTIONS NURSING ACTIONS Antidepressants RATIONALE/EXPLANATION 1. With antidepressants for depression. Mix sertraline oral concentrate (20 mg/mL) in 4 oz of water. blood levels of nefazodone are higher in clients with cirrhosis. improved sleep patterns. observe for decreases in manic behavior and mood swings. a benzodiazepine or an antipsychotic drug is usually given to reduce agitation and control behavior until the lithium takes effect. To prevent insomnia Manufacturer’s recommendation To aid sleep and decrease daytime sedation To decrease gastrointestinal (GI) effects (eg. b. With antidepressants for anxiety disorders. Also. In addition. Therapeutic effects do not occur until approximately 7 to 10 days after therapeutic serum drug levels (1–1. ginger ale. Give most selective serotonin reuptake inhibitors (SSRIs) once daily in the morning.CHAPTER 10 DRUGS FOR MOOD DISORDERS: ANTIDEPRESSANTS AND MOOD STABILIZERS 177 Tricyclic antidepressants are also less readily metabolized with severe hepatic impairment (eg. the nurse needs to observe the client’s response and assess for suicidal thoughts or plans. improved appearance. decreased somatic complaints. The decision to continue or start an antidepressant drug should be based on a thorough assessment of the client’s condition. This increases the risk of adverse effects such as sedation and hypotension. nausea and vomiting) Therapeutic effects occur 2 to 4 weeks after drug therapy is started. decreased anxiety. physical activity.2 mEq/L for maintenance therapy) are attained. the nurse should encourage the client to continue taking the medication.5 mEq/L with acute mania. Use in Critical Illness Critically ill clients may be receiving an antidepressant drug when the critical illness develops or may need a drug to combat the depression that often develops with major illness. the nurse may need to remind the client that it usually takes 2 to 4 weeks to feel better.6–1. Nefazodone has been associated with a few cases of liver failure and should not be given to clients with severe liver impairment. If an antidepressant is given. other drugs being given. lemon/lime soda. observe for statements of feeling better or less depressed. In mania. and other factors. d. cautious and slow and the client’s responses carefully monitored because critically ill clients are often frail and unstable. Administer accurately a. Depression often accompanies any serious physical illness and may occur in many other circumstances as well. 2. Observe for therapeutic effects a. Give venlafaxine and lithium with food. with multiple organ dysfunctions. severe cirrhosis). c. (continued ) . or orange juice only. Give tricyclic antidepressants (TCAs) and mirtazapine at bedtime. lemonade.

headache. sexual dysfunction. dizziness. hallucinations. dizziness. insomnia. effects on cardiac conduction and does not cause orthostatic hypotension. ataxia. dry mouth. observe for sedation. d. diarrhea. diarrhea. SSRIs and other newer drugs are less likely to cause significant sedation. hypotension. b. and insomnia are common with venlafaxine. dry mouth. skin rash. nausea and vomiting. photosensitivity. Compared with the TCAs. nervousness. GI upset. Hypoglycemia results from a drug-induced reduction in blood sugar. and insomnia. and usually subside during the first few weeks of drug therapy. tachycardia. agitation. headache. Toxic symptoms occur at serum drug levels above 2. orthostatic hypotension (3) GI effects—nausea. headache. nausea and vomiting. abdominal pain. With TCAs. muscular weakness. occur at therapeutic serum drug levels (0. slurred speech. incoordination. dry mouth. and weight gain (2) More severe nausea and diarrhea. sexual dysfunction. Cardiovascular effects are most serious in overdose. constipation. diarrhea. nervousness. fatigue. With mirtazapine. nausea. 20–120 mg daily. hypoglycemia.8–1. Common effects are drowsiness. skin rash. muscle twitching and tremors. Symptoms listed in (2) occur at higher serum drug levels (1. With monoamine oxidase inhibitors (MAOIs). tachycardia. vomiting. constipation. dizziness. and orthostatic hypotension are common with nefazodone. or discontinuing the drug temporarily. Adverse effects are most likely to occur if recommended doses are exceeded. With SSRIs nefazodone and venlafaxine. and weight loss. urinary retention. Observe for adverse effects a.5 mEq/L). edema. diarrhea. Most adverse effects result from anticholinergic or antiadrenergic activity. diarrhea. polyuria. Propranolol (Inderal). Severe adverse effects may be managed by decreasing lithium dosage.178 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM NURSING ACTIONS 3. confusion. and weight gain. observe for: (1) Central nervous system (CNS) effects—drowsiness. weight gain c.5–2. Lithium mobilizes white blood cells (WBCs) from bone marrow to the bloodstream. hand tremors. hypotension. nausea. confusion. Has CNS depressant and anticholinergic effects. dry mouth. urinary retention. if any. dry mouth. insomnia (2) GI effects—nausea. polydipsia. sedation. f. dark urine. Symptoms listed in (1) are common. dizziness. Most clients who take lithium experience adverse effects. CNS stimulation (agitation. vomiting. Note that bupropion has few. Although numerous adverse effects may occur. GI upset. poor memory (2) Cardiovascular effects—cardiac arrhythmias. With bupropion. vomiting.5 mEq/L. they are usually less serious than those occurring with most other antidepressants. omitting a few doses. RATIONALE/EXPLANATION GI upset and diarrhea are common with SSRIs. blurred vision. constipation (3) Cardiovascular effect—orthostatic hypotension (4) Hepatic effect—liver failure (anorexia. observe for dizziness. Maximum increase in WBCs occurs in 7 to 10 days. and cardiac arrhythmias but are more likely to cause nausea. drowsiness. nausea. weight gain. anorexia. hyperactivity. tinnitus. observe for blurred vision. may be given to control tremors. e. urinary retention. constipation (4) Other effects—blurred vision. dizziness. delusions). observe for: (1) CNS effects—anxiety. observe for: (1) Metallic taste. increased muscle tone Anticholinergic effects are common. observe for seizure activity. Nausea may be decreased by giving lithium with meals.2 mEq/L). insomnia. With nefazodone. hypotension. With lithium. jaundice) g. dizziness. (3) Leukocytosis (continued ) .

increasing risk of heart block Additive anticholinergic effects (eg. above. Drugs that increase the effects of mirtazapine. benzodiazepine antianxiety and hypnotic agents. Drugs that increase effects of TCAs: (1) Antiarrhythmics (eg. phenylephrine). dry mouth. phenytoin. nefazodone or venlafaxine. Drugs that decrease effects of TCAs: (1) Carbamazepine. May increase serum drug levels of SSRIs by slowing their metabolism SSRIs and MAOIs should not be given concurrently or close together because serious and fatal reactions have occurred. These drugs induce liver enzymes that accelerate the metabolism of the SSRIs. and venlafaxine: (1) MAOIs See SSRIs. meperidine (continued ) . and an MAOI should be stopped at least 14 days before starting mirtazapine. Drugs that increase effects of MAOIs: (1) Anticholinergic drugs (eg. nefazodone. and death have occurred with concurrent use. constipation) Additive hypotension Increases risks of toxicity by decreasing hepatic metabolism and increasing blood levels of TCAs Additive sedation and CNS depression TCAs should not be given with MAOIs or within 2 weeks after an MAOI drug. urinary retention. phenytoin. The reaction. antipsychotic agents.CHAPTER 10 DRUGS FOR MOOD DISORDERS: ANTIDEPRESSANTS AND MOOD STABILIZERS 179 NURSING ACTIONS 4. Additive effects on cardiac conduction. attributed to excess serotonin and called the serotonin syndrome. an SSRI should not be started for at least 2 weeks after an MAOI is discontinued. alcohol (some beers and wines). rifampin (2) Cyproheptadine c. epinephrine. Inhibit metabolism of TCAs These drugs induce drug-metabolizing enzymes in the liver. procainamide) (2) Antihistamines. hyperpyrexia. disopyramide. To avoid this reaction. and other drugs with anticholinergic effects (3) Antihypertensives (4) Cimetidine (5) CNS depressants (eg. nicotine (cigarette smoking) f. convulsions. b. This is an antihistamine with antiserotonin effects. atropine. muscle spasm. and an MAOI should not be started for at least 2 weeks after an SSRI has been discontinued (5 weeks with fluoxetine. Observe for drug interactions a. opioid analgesics) (6) MAOIs (7) SSRIs e. alcohol. and coma. rifampin. TCAs) (2) Adrenergic agents (eg. These drugs and MAOIs should not be given concurrently or close together because serious and fatal reactions have occurred. may cause hyperthermia. quinidine. atropine. agitation. Additive anticholinergic effects Hypertensive crisis and stroke may occur. blurred vision. Drugs that decrease effects of SSRIs: (1) Carbamazepine. levodopa. Drugs that increase effects of SSRIs: (1) Cimetidine (2) MAOIs RATIONALE/EXPLANATION Drug interactions with the SSRIs vary with individual drugs. Mirtazapine should be stopped at least 14 days and nefazodone or venlafaxine at least 7 days before starting an MAOI. delirium. d. because of its long half-life). which increases the rate of TCA metabolism and elimination from the body.

No. 568–574. Often they can be forgotten or taken away with the food tray. captopril) (2) Diuretics (eg. 12. sodium chloride (in excessive amounts). Southern Medical Journal. S. L. drugs with a high sodium content (eg. & Switzer. 3. What is the advantage of giving a TCA at bedtime rather than in the morning? 8. Washington. ticarcillin). S. mirtazapine. special care should be taken to supervise all medications. D. what kinds of appearances or behaviors may indicate depression? 2. [On-line] Available: . 200. W. List the main elements of treatment for antidepressant overdoses. 763–766. Jordan’s sleeping difficulty could be a symptom of her depression or a side effect of the Prozac. and how may they be minimized? 13. Consumer use of St.. How do the drugs act to relieve depression? 5. (2000). Increased risk of hyperglycemia May increase effects of lithium and are sometimes combined with lithium for this purpose. 756–812. 4th ed. Pharmacologic management of acute and chronic pain. If it is a drug side effect. Baldwin. it might help to take the drug in the morning. hydrochlorothiazide) RATIONALE/EXPLANATION Decrease renal clearance of lithium and thus increase serum lithium levels and risks of toxicity. furosemide. and venlafaxine. How do the SSRIs differ from TCAs? 10. pp. What are the major groups of antidepressant drugs? 4. When a client begins antidepressant drug therapy. E. Sommi. (2001). & Barkin.C. Drugs that increase effects of lithium: (1) Angiotensin-converting enzyme inhibitors (eg. Increase neurotoxicity and cardiotoxicity of lithium by increasing excretion of sodium and potassium and thereby decreasing excretion of lithium. Ms. giving the client more energy to carry out suicidal actions. 94(8). The dosage is usually not increased for 3 to 4 weeks. Depressed clients could save up medication to commit suicide by overdosing. What are common adverse effects of TCAs. Nursing Notes: Apply Your Knowledge Answer: Prozac has a long half-life (24 to 72 hours). For a client taking an MAOI. why is it important to explain that relief of depression may not occur for a few weeks? 6. Missing a dose of a medication can affect therapeutic blood levels. so it takes longer than a week to reach steady state. D. what information would you provide for preventing a hypertensive crisis? 9. Beckman. What is the nurse’s role in assessing and managing depression in special populations? In the home setting? SELECTED REFERENCES Review and Application Exercises 1. Pharmacotherapy.: American Psychiatric Association. and how may they be minimized? 7. Barkin. Decrease renal clearance of lithium and thus increase serum levels and risks of lithium toxicity. (2000). D. (2000). It is important to teach all clients beginning therapy with antidepressants that they may not see significant improvement in their depression for a number of weeks. J. The risk for this increases as the antidepressant drugs start to work. These drugs also may precipitate a manic episode and increase risks of hypothyroidism. Text Revision (DSM-IV-TR). Drugs that decrease effects of lithium: (1) Acetazolamide. John’s Wort. nefazodone. Is antidepressant drug therapy indicated for most episodes of temporary sadness? Why or why not? American Psychiatric Association. In this situation. 20(5). Increase excretion of lithium (3) Nonsteroidal anti-inflammatory drugs (4) Phenothiazines (5) TCAs h. Adverse drug reactions to newer antidepressants. Wake Jane up and firmly encourage her to take her medications as you watch. Adverse Drug Reaction Bulletin. compare with the SSRIs in terms of adverse effects and adverse drug–drug interactions? 11. How do the newer drugs. ISSN 0044-6394. What are common adverse effects of lithium. R. R. Diagnostic and statistical manual of mental disorders.180 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM NURSING ACTIONS g. During the initial assessment of any client. theophylline How Can You Avoid This Medication Error? Answer: Do not leave medications at the bedside of a client.

C. Department of Health and Human Services.08.com/PP/Pharmacotherapy/2000/v20. W. Accessed Nov. American Journal of Nursing. In E. A. Herfindal & D. St. (1999). 1203–1216.. Kim. New Rochelle. Agency for Health Care Policy and Research. & Nemeroff. E. & Avila. 2: Treatment of major depression. Accessed March 18. B. PA: Springhouse Corporation. Sadek. L.medscape. (2000). & Sumners.) (2001). St. Louis: Facts and Comparisons. 48–54. A. (Updated monthly). Textbook of therapeutics: Drug and disease management.html. ginkgo. MD: U.com Medscape/psychiatry/Treatment Update/2000/tu03/public/toc-tu03. M. (Ed. G. St. 101(4). NY: The Medical Letter. R. J. 2001.). 93-0551. Professional’s handbook of complementary & alternative medicines. (Ed. [On-line] Available: http://www. 7th ed. Drug facts and comparisons.medscape. pp. (2001). .beck-01.beck/pharm2005.). R. Springhouse. Depression Guideline Panel.S. Waddell. T.html. Three herbs you should get to know: Kava. (2000). D. Rockville.. Louis: Facts and Comparisons. Gourley (Eds. DerMarderosian.CHAPTER 10 DRUGS FOR MOOD DISORDERS: ANTIDEPRESSANTS AND MOOD STABILIZERS 181 http://www. Hummel. D. B. N. Update on the neurobiology of depression. (1993). Public Health Service. Philadelphia: Lippincott Williams & Wilkins. 2001. Handbook of adverse drug interactions. (2001). AHCPR publication No.n05/pharm 2005. John’s Wort. Inc. L. Stimmel. R. Medscape article. Mood disorders. Clinical practice guideline: Depression in primary care. Fetrow. The review of natural products. C.

Describe strategies for prevention and treatment of status epilepticus. stroke. 3. brain tumor) or alcohol and other drug effects. which could increase risk of seizures.chapter 11 Antiseizure Drugs Objectives AFTER STUDYING THIS CHAPTER. Identify types and potential causes of seizures. The terms seizure and convulsion are often used interchangeably. Differentiate between older and newer antiseizure drugs. treatment of the underlying problem or temporary use of an AED may relieve the seizures. Discuss major factors that influence choice of an antiseizure drug for a client with a seizure disorder. it is often caused by an acquired neurologic disorder (eg. isoniazid. In these instances. management of Jamie during a seizure to ensure safety. 2. although they are not the same. who will be the primary caregiver. methods to avoid skipping doses. Differentiate characteristics and effects of commonly used antiseizure drugs. Reflect on: ᮣ How you would feel as a new parent if your infant were diagnosed with a seizure disorder. cocaine. Fever is a common cause during late infancy and early childhood. methylphenidate. Critical Thinking Scenario You are caring for 6-month-old Jamie. Epilepsy is characterized by abnormal and excessive electrical discharges of nerve cells. The incidence of epilepsy is A . prioritize your teaching plan. 7. theophylline). and drug therapy is usually required. When epilepsy begins in infancy. fever. Seizures may occur as single events in response to hypoglycemia. recurrent pattern. What would be your most significant fears? ᮣ Given 15 minutes for discharge teaching. and inherited forms usually begin in childhood or adolescence. It is diagnosed by clinical signs and symptoms of seizure activity and by the presence of abnormal brain wave patterns on the electroencephalogram. overdoses of numerous drugs (eg. amphetamine. Discuss the use of antiseizure drugs in special populations. electrolyte imbalances. He will be discharged today to his single. who was just diagnosed with tonic-clonic seizures. causes include developmental defects. considering the following: safe administration of an anticonvulsant medication to a 6-month-old. or birth injury. 182 Epilepsy When seizures occur in a chronic. antipsychotics. Compare advantages and disadvantages between monotherapy and combination drug therapy for seizure disorders. A seizure involves a brief episode of abnormal electrical activity in nerve cells of the brain that may or may not be accompanied by visible changes in appearance or behavior. A convulsion is a tonic-clonic type of seizure characterized by spasmodic contractions of involuntary muscles. metabolic disease. and withdrawal of alcohol or sedative-hypnotic drugs. the disorder is called epilepsy. THE STUDENT WILL BE ABLE TO: 1. lithium. lidocaine. The cause is unknown in 60% to 80% of children and adolescents and 50% of older adults. Apply the nursing process with clients receiving antiepileptic drugs. When epilepsy begins in adulthood. 8. SEIZURE DISORDERS ntiseizure drugs are also called antiepileptic drugs (AEDs) or anticonvulsants. He was started on valproic acid (Depakene) 30 mg qid and has only had one seizure during his 4-day hospitalization. 5. teenaged mother. 6. head injury. 4.

consciousness is not impaired. Some seem able to suppress abnormal neuronal firing without suppressing normal neurotransmission. more toxic drugs are virtually eliminated from clinical usage and the roles of newer drugs are being defined. the drugs are thought to suppress seizures by decreasing movement of ions into nerve cells. In a person taking medications for a diagnosed seizure disorder. AEDs also are used to stop acute. Partial seizures begin in a specific area of the brain and often indicate a localized brain lesion such as birth injury. febrile seizures (ie. In addition to maintenance treatment of epilepsy. swallowing. Some people are subject to mixed seizures. or aversive movements. or tumor. In other clients. appropriate treatment is instituted. consideration of monotherapy versus two or more drugs. theophylline). repetitive. The actions of both sodium channel blockers (eg. In simple partial seizures. Increasing the activity of gamma-aminobutyric acid (GABA). Attempts to overcome these difficulties have led to the development of several new drugs in recent years. Other types of generalized seizures include the myoclonic type (contraction of a muscle or group of muscles) and the akinetic type (absence of movement). hypoxia. phenobarbital. The clonic phase is characterized by rapid rhythmic and symmetric jerking movements of the body. GABA. regardless of whether they have a diagnosed seizure disorder. especially the chronic recurring seizures of epilepsy. and inappropriate to the situation. and overdoses of drugs (eg. However. and undesirable drug interactions among AEDs and between AEDs and other drugs. during which the person becomes cyanotic. tonic-clonic convulsions and status epilepticus. staring expression with or without blinking of the eyelids. Movements are usually automatic. tiagabine. a social stigma and adverse drug effects that often lead to poor client compliance. trauma. twitching of the head or arms. a longer-acting drug. and cardiac dysrhythmias may also occur. including trials of different drugs. the major excitatory neurotransmitter. lamotrigine. valproate) and newer drugs (gabapentin. tonic-clonic seizures that occur in the absence of other identifiable causes) are the most common form of epilepsy. Indications for particular drugs depend on the types and severity of seizures involved. Epilepsy is broadly classified as partial and generalized seizures. such as ANTISEIZURE DRUGS Antiseizure drugs can usually control seizure activity but do not cure the underlying disorder. Once acute seizure activity is controlled. cocaine. altering the activity of neurotransmitters (eg. Hypotension. Generalized seizures are bilateral and symmetric and have no discernible point of origin in the brain. such as chewing. characterized by abrupt alterations in consciousness that last only a few seconds. the drugs are thought to stabilize neuronal membranes and decrease neuronal firing in response to stimuli. lack of seizure control while drugs are being selected and dosages adjusted. alcohol withdrawal. and absence of respiration. benzodiazepines and most of the newer AEDs) raise the amount of stimulation required to produce a seizure (called the seizure threshold). The drug of choice for this purpose is an intravenous (IV) benzodiazepine. The tonic phase involves sustained contraction of skeletal muscles. In children. topiramate. such as opisthotonos. Drug therapy of epilepsy is rapidly evolving as older. systemic or central nervous system (CNS) infections. for both clinicians and clients. also decrease nerve cell excitability. older drugs that are still commonly used (phenytoin. There is a high risk of permanent brain damage and death unless prompt. in complex partial seizures. phenytoin. Status epilepticus is a life-threatening emergency characterized by generalized tonic-clonic convulsions lasting for several minutes or occurring at close intervals during which the client does not regain consciousness. oxcarbazepine. blocking these ions decreases responsiveness to stimuli and results in stabilized. the level of consciousness is decreased. stroke. carbamazepine. In this chapter. a brief warning. Behavior is sometimes so bizarre that the person is diagnosed as psychotic or schizophrenic. Because movement of sodium and calcium ions is required for normal conduction of nerve impulses.CHAPTER 11 ANTISEIZURE DRUGS 183 higher in young children and older adults than in other age groups. Numerous difficulties. abnormal postures. dosage over a period of time. ethosuximide. such as a flash of light or a specific sound. The most common type is the tonic-clonic or major motor seizure. and other motor movements. less excitable cell membranes. For example. The person may have a blank. oxcarbazepine is approved for monotherapy and studies indicate that most of the other newer drugs may be effective as monotherapy in some types of seizures. levetiracetam. causes of status epilepticus include brain trauma or tumors. the need to titrate . They produce symptoms ranging from simple motor and sensory manifestations to more complex abnormal movements and bizarre behavior. oxcarbazine) and GABA enhancers (eg. usually lorazepam. Tonic-clonic seizures are sometimes preceded by an aura. the most common cause of status epilepticus is abruptly stopping AEDs. or a combination of these mechanisms. Mechanisms of Action Although the exact mechanism of action is unknown for most AEDs. zonisamide) are discussed. the major inhibitory neurotransmitter in the brain. Overall. glutamate). most of the newer drugs are indicated for use with one or two other AEDs to treat more severe seizure disorders that do not respond to a single drug. and decreasing the activity of glutamate. have been associated with AED therapy. Indications for Use The major clinical indication for AEDs is the prevention or treatment of seizures. Another type of generalized seizure is the absence seizure.

5 hours with the liquid suspension. Prompt-acting forms reach peak plasma levels in 2 to 3 hours. vomiting). especially in children. oxcarbazepine. Intramuscular phenytoin is poorly absorbed and not recommended. It is approved for treatment of status epilepticus and for short-term use in clients who cannot take oral phenytoin.9% sodium chloride solution. lethargy) and gastrointestinal (GI) tract (nausea. The most common adverse effects of phenytoin affect the CNS (eg. Because the drugs are so diverse. carbamazepine. In addition to treatment of seizure disorders. Carbamazepine (Tegretol) is used. especially in adults. and other symptoms). Phenytoin is available in generic and brand name capsules. If a client is stabilized on a generic formulation and switches to Dilantin. or pancreatitis. topiramate. It is given orally and peak blood levels are reached in about 1. Carbamazepine is contraindicated in clients with previous bone (text continues on page 188) . Phenytoin may interact with many other drugs. Gingival hyperplasia. lamotrigine. is also common. leukopenia. Additional contraindications include phenytoin with sinus bradycardia or heart block. Because it induces its own metabolism. ataxia. It is often the initial drug of choice. They are also used in the management of chronic neuropathic pain. and drowsiness as common adverse effects. ethosuximide. Some of the newer AEDs are being tested for effectiveness in relation to bipolar. Gabapentin is also being used. The manufacturer recommends that all dosages be expressed in phenytoin equivalents (PE). in addition to seizure disorders. Thus. In contrast to other preparations of injectable phenytoin. Phenytoin. Phenytoin (Dilantin). 4 to 5 hours with conventional tablets. AEDs are used to treat bipolar disorder (eg. gabapentin. carbamazepine with bone marrow depression (eg. loss of therapeutic effectiveness. Consequently. mainly because it induces drug-metabolizing enzymes in the liver. nephritis. For IV administration. Contraindications to Use AEDs are contraindicated or must be used with caution in clients with CNS depression. arthralgia. there is a risk of lower serum phenytoin levels. Phenytoin. Fosphenytoin is available in 2-mL and 10-mL vials with 50 mg PE/mL (fosphenytoin 50 mg PE = phenytoin 50 mg). It is metabolized in the liver to inactive metabolites that are excreted in the urine. carbamazepine. Fosphenytoin (Cerebyx) is a prodrug formulation that is rapidly hydrolyzed to phenytoin after IV or intramuscular (IM) injection. hepatitis. AEDs also are used prophylactically in clients with brain trauma from injury or surgery. Carbamazepine is approved for treatment of the pain associated with trigeminal neuralgia. there is a risk of higher serum phenytoin levels and toxicity. a chewable tablet. Also. some may cause serious or life-threatening adverse effects such as cardiac dysrhythmias. is one of the oldest and most widely used AEDs. an oral suspension. many other drugs can affect phenytoin metabolism and protein binding. drowsiness. both AEDs and non-AEDs. to treat trigeminal neuralgia and bipolar disorder. and tiagabine and valproic acid with liver disease. and infused at a maximal rate of 150 mg PE/minute. the prototype. types of seizures for which the drugs are used and dosages are listed in Drugs at a Glance: Antiseizure Drugs. some people suggest they be called neuromodulators or neurostabilizers rather than AEDs or anticonvulsants.184 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM phenytoin or fosphenytoin. and long-acting forms in about 12 hours.5–25 mg PE/mL. but it is not approved for this indication and is not considered better than carbamazepine. lamotrigine. neuropathic pain. it can increase the metabolism of itself and many other drugs. The injectable solution is highly irritating to tissues and special techniques are required when the drug is given intravenously (IV). Most are metabolized in the liver. Serious reactions are uncommon but may include allergic reactions. INDIVIDUAL ANTISEIZURE DRUGS Most AEDs are well absorbed with oral administration and are usually given by this route. It is metabolized in the liver to an active metabolite. All of the drugs must be used cautiously during pregnancy because they are teratogenic in animals. tiagabine. There may also be differences in bioavailability among generic formulations manufactured by different companies. In addition to treatment of seizure disorders. and valproate are contraindicated in clients who have experienced a hypersensitivity reaction to the particular drug (usually manifested by a skin rash. and can be given IV more rapidly. Most produce ataxia (impaired muscular coordination such as a staggering gait when trying to walk). and an injectable solution. bone marrow depression. although few studies validate their effectiveness for this purpose. topiramate and zonisamide are contraindicated or must be used cautiously in clients with hepatic or renal impairment. fosphenytoin can be diluted to a concentration of 1. and other disorders. the rate and extent of absorption vary with the drug formulation. agranulocytosis). an overgrowth of gum tissue. they cannot be adequately discussed as groups. carbamazepine and valproate) although they are not FDA-approved for this purpose. confusion. and mental confusion. If a client takes Dilantin and switches to a generic form. and seizures. With oral phenytoin. its half-life shortens with chronic administration. levetiracetam. a few are eliminated mainly through the kidneys. bone marrow depression. Phenytoin is highly bound (90%) to plasma proteins. it is sometimes used to treat cardiac dysrhythmias. Clients should not switch between generic and trade name formulations of phenytoin because of differences in absorption and bioavailability. and 3 to 12 hours with extended-release forms (tablets and capsules). Because the drugs are being used for other indications than seizure disorders. the drugs are described individually. dizziness. is given to prevent recurrence. fosphenytoin causes minimal tissue irritation. can be diluted with 5% dextrose or 0.

2 mg/kg/d >12 y: PO same as adults 9–12 y: PO maximal initial dose 7. in 3 divided doses. every 2–5 min up to a maximum of 5 mg 5 y and older: IV 1 mg every 2–5 min up to a maximum of 10 mg. increased up to 1800 mg/d if necessary. Does not cause significant drug–drug interactions (continued ) . 17–51 µmol/L). in 3 or 4 divided doses Remarks • Available in oral and chewable tablets. Repeat in 2–4 hours if necessary. PO 200 mg daily. maximum dose. increased at weekly intervals until seizures are controlled or toxicity occurs. in 3 divided doses. with other AEDs PO 1. and a suspension of 100 mg/5 mL. increased by 0.5 mg/d every 3–7 days if necessary. Schedule IV drug Clonazepam (Klonopin) Clorazepate (Tranxene) Myoclonic or akinetic seizures. maximum dose. maximum dose. can also be given IM Gabapentin (Neurontin) Partial seizures. 100 mg/24 h. Intervals between doses should not exceed 12 h. 30 mg. 3–12 y: 10–15 mg/kg/d. • The suspension is absorbed more rapidly and produces higher peak drug levels than tablets. in 3 or 4 divided doses Trigeminal neuralgia. approximately 750–1000 mg/d Dosage not established Schedule IV drug Schedule IV drug Available in oral capsules and syrup Therapeutic serum drug level is 40–80 mcg/mL. also may be effective in myoclonic and akinetic epilepsy Fosphenytoin (Cerebyx) Status epilepticus and short-term use in clients who cannot take oral phenytoin PO 0. increase to 1000 mg daily if necessary.5 mg 3 times daily.5 mg/d every 3–7 days if necessary. extended-release tablets and capsules.5 mg over 2–3 min. status epilepticus.5 mg every week.5 mg every week. may increase to 1000 mg daily for children 12–15 years and 1200 mg for children over 15 y. increased by 0. IV. in 3 divided doses (same as adults). 90 mg/d IV 5–10 mg no faster than 2 mg/min. if necessary. maximum dose.03 mg/kg/d. 0. at a rate of 100–150 mg PE/min PO 900 mg daily. increased gradually to 1200 mg if necessary Children >12 y: PO 200 mg twice daily. if necessary. generalized tonicclonic. PO 200 mg twice daily.5 mg two times daily.25– 0. repeat every 5–10 min if needed. with other AEDs >12 y: PO 900–1800 mg/d. possibly effective in generalized tonic-clonic and psychomotor seizures Partial seizures. 20 mg/d PO maximal initial dose 7. increased by 250 mg weekly until seizures are controlled or toxicity occurs. PO initially 250 mg/d. PO initially 500 mg/d. if necessary 6–12 y: PO 100 mg twice daily (tablet) or 50 mg 4 times daily (suspension).CHAPTER 11 ANTISEIZURE DRUGS 185 Drugs at a Glance: Antiseizure Drugs Routes and Dosage Ranges Generic/Trade Name Carbamazepine (Tegretol) Types of Seizures Used to Treat Partial. Much easier to give IV than phenytoin. and mixed seizures Adults Epilepsy. increased if necessary. Diazepam (Valium) Acute convulsive seizures. 60 mg/d >30 d and <5 y: IV 0. alone or with other AEDs. maximum dose. Intervals between doses should not exceed 12 h. increased by 7. 1500 mg/d Nonemergent seizures. increased by 7. maintenance dose 4–6 mg PE/kg/d.5 mg/d.01–0. status epilepticus Ethosuximide (Zarontin) Absence seizures. IV 15–20 mg PE/kg. maximum dose. increased gradually to 600– 1200 mg daily if needed. maximum dose.2–0. • Therapeutic serum drug level is 4 to 12 mcg/mL (SI units. Repeat in 2–4 hours if necessary. maximum dose. IM loading dose 1–20 mg PE/kg.

186 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Drugs at a Glance: Antiseizure Drugs (continued ) Routes and Dosage Ranges Generic/Trade Name Types of Seizures Used to Treat Adults Renal impairment: Crcl >60 mL/min. PO 25 mg every other day for 2 wk. 500–1500 mg.15 mg/kg/d in 1 or 2 doses for 2 wk. on hemodialysis. 250–500 mg End-stage renal disease. PO 300–500 mg daily in 1 or 2 doses Dosage not established Valproic acid slows lamotrigine’s metabolism by approximately 50%. for 2 wk Maintenance dose. 500– 1000 mg. Crcl 30–60 mL/min.5–5 mg. PO 100–400 mg daily in 1 or 2 divided doses With valproic acid. then 50 mg twice daily (100 mg/d) for 2 wk. Crcl <30. If calculated dose is 2. initially. with other AEDs Levetiracetam (Keppra) Partial seizures. With AEDs including valproic acid: PO 25 mg every other day for 2 wk. 250–750 mg. 400 mg 3 times daily (1200 mg/d). For patients on hemodialysis. then 25 mg once daily for 2 wk. Crcl 15–30 mL/min. then 0. if necessary. increased by 1000 mg/d every 2 wk. 200– 300 mg after each 4 h of hemodialysis. Crcl 50–80. rounded to nearest 5 mg. PO 0. 500–1000 mg. with other AEDs PO 500 mg twice daily initially. 100–150 mg/d in 2 divided doses. If lamotrigine is combined with other AEDs plus valproic acid. then 25 mg daily for 2 wk Maintenance dose. with a supplemental dose of half the total daily dose (250–500 mg) 2–12 y: With enzymeinducing AEDs. PO 50 mg daily for 2 wk. With AEDs other than valproic acid: PO 50 mg once daily for 2 wk. give 5 mg on alternate days for 2 wk. Children Remarks Lamotrigine (Lamictal) Partial seizures. A newer drug that may have several advantages over older agents . 300 mg every other day. 300 mg once daily. dosage must be substantially reduced. then 100 mg daily in 2 divided doses for 2 wk Maintenance dose.3 mg/kd/d in 1 or 2 doses. 300 mg 2 times daily (600 mg/d). 3000 mg daily Renal Impairment: Crcl >80. initially. Usual maintenance dose. with other AEDs Lennox-Gastaut syndrome. then increase by 25 to 50 mg/d every 1–2 wk to a maintenance dose. PO 5–15 mg/kg/d in 2 divided doses >12 y: With enzymeinducing AEDs. Crcl <15 mL/min. Usual maintenance dose. Maximum dose. Crcl 30–50. 300–500 mg/d in 2 divided doses. then increase by 100 mg/d at weekly intervals to a maintenance dose.

with other AEDs PO 25–50 mg daily. Most experience obtained in patients receiving at least one concomitant enzyme-inducing AED. increased by 25–50 mg per week until response. and 600-mg scored tablets and a 60 mg/mL fruitflavored suspension Serum drug levels of 10–25 mcg/mL are in the therapeutic range • Available in chewable tablets. 300-. and solution for injection • Therapeutic serum level is 5–20 mcg/mL (SI units 40–80 µmol/L). with other AEDs PO 4 mg daily for 1 wk. PO 300 mg twice daily (600 mg/d) and increased slowly until response achieved PO 100–300 mg daily in 2–3 divided doses PO 100 mg three times daily initially. 400 mg daily in 2 divided doses 2–16 y: PO wk 1. maximum dose 300 mg/d Phenytoin (prototype. with other AEDs in children 4–16 years old With other AEDs. or 5% dextrose in water. diluted in an equal amount of sterile water for injection. then increased by 4–8 mg/wk up to a maximum of 32 mg/d in 2 to 4 divided doses <12 y: not recommended A newer drug with possible advantages over older drugs Available in 150-. increase by 1–3 mg/kg/d at 1. Usual dose. Phenobarbital Generalized tonic-clonic and partial seizures Generalized tonic-clonic and some partial seizures Prevention and treatment of seizures occurring during or after neurosurgery PO 5 mg/kg per day in 2–3 divided doses PO 4–7 mg/kg/d in divided doses.CHAPTER 11 ANTISEIZURE DRUGS 187 Drugs at a Glance: Antiseizure Drugs (continued ) Routes and Dosage Ranges Generic/Trade Name Lorazepam (Ativan) Types of Seizures Used to Treat Acute convulsive seizures. increased to 8 mg/d in 2 divided doses for 1 wk. Topiramate (Topamax) Partial seizures. Dilantin) Tiagabine (Gabitril) Partial seizures. immediate-release and extended-release capsules. those receiving valproate monotherapy) may require lower doses or a slower dose titration. Titrate to reach target dose over 2 wk. oral suspension. status epilepticus Adults IV 2–10 mg.or 2-wk intervals until response. and injected over 2 min PO 600 mg twice daily (1200 mg/d) Severe renal impairment (Crcl <30 mL/min). increased by 4–8 mg/wk until desired effect. not to exceed 600 mg twice daily. maximum dose 56 mg/d in 2–4 divided doses 12–18 y: PO 4 mg daily for 1 wk. in 2 divided doses (continued ) . 0. 25 mg every PM. PO 8–10 mg/kg/d. Concentrations at or above the upper therapeutic level may be associated with toxicity. as monotherapy or with other AEDs in adults.9% sodium chloride injection. 300 mg (long-acting) once daily as maintenance IV 100 mg q6–8h. Use in noninduced patients (eg. maximum 50 mg/min Children Dosage not established Remarks Schedule IV drug Oxcarbazepine (Trileptal) Partial seizures. Usual dose 5–9 mg/kg/d.

In status epilepticus. about 20% is excreted unchanged through the kidneys. diluted in 5% dextrose or 0. and lorazepam (Ativan) are benzodiazepines (see Chap. loss of muscle coordination. abnormal vision. Zonisamide (Zonegran) Partial seizures. it is followed with a long-acting anticonvulsant. 600 mg daily <16 y: not recommended AED. doses are in valproic acid equivalents. Ethosuximide may be used with other AEDs for treatment of mixed types of seizures. especially the life-threatening seizures of status epilepticus. clorazepate (Tranxene). marrow depression or hypersensitivity to carbamazepine and in clients receiving monoamine oxidase inhibitors (MAOIs). until seizures controlled. Usual daily dose. It is well absorbed with oral administration and reaches peak serum levels in 3 to 7 hours. clonazepam produces physical dependence and withdrawal symptoms. such as phenytoin. vomiting. Crcl. mixed. Ethosuximide (Zarontin) is the AED of choice for absence seizures. The elimination half-life is approximately 30 hours in children and 60 hours in adults. adverse effects occur. tremor. antiepileptric drug. as the sodium salt (sodium valproate). Give amounts >250 mg/d in divided doses. Because the drug is eliminated only by the kidneys. Divalproex sodium (Depakote enteric-coated tablets) Types of Seizures Used to Treat Absence. switch to oral product when possible. and pruritus. drowsiness. PE. MAOIs should be discontinued at least 14 days before carbamazepine is started. nausea. Clonazepam and clorazepate are used in long-term treatment of seizure disorders. creatinine clearance. diazepam (Valium). Because of clonazepam’s long halflife. Abrupt withdrawal may precipitate seizure activity or status epilepticus. a steady-state serum concentration is reached in about 5 days. Gabapentin reportedly does not cause significant drug–drug interactions. These products may contain valproic acid as the acid. Lorazepam has become the drug of choice for status epilepticus because its effects last longer than those of diazepam. 8) used in seizure disorders. Sodium valproate (Depakene syrup. gingivitis. increase by 100 mg/d every 1–2 wk if necessary. or the maximum dose (60 mg/kg/d) is reached. depending on creatinine clearance. in divided doses IV client’s usual dose. Adverse effects include dizziness. is not appreciably metabolized. or a combination of the two (divalproex sodium). fatigue.188 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Drugs at a Glance: Antiseizure Drugs (continued ) Routes and Dosage Ranges Generic/Trade Name Valproic acid (Depakene capsules). increase weekly by 5–10 mg/kg/d. Diazepam has a short duration of action and must be given in repeated doses. Diazepam and lorazepam are used to terminate acute convulsive seizures. Clonazepam (Klonopin). Several formulations of valproic acid are available in the United States. with other AEDs PO 100–200 mg daily as a single dose or as 2–3 divided doses. The elimination half-life is 5 to 7 hours with normal renal function and up to 50 hours with impaired renal function. dosage must be reduced in clients with renal impairment. and is eliminated by the kidneys as unchanged drug. Gabapentin (Neurontin) is used with other AEDs for treatment of partial seizures. Depacon injection). Tolerance to antiseizure effects develops with long-term use. alone or with other AEDs. circulates largely in a free state because of minimal binding to plasma proteins. As with other benzodiazepines. maximum dose. . Most adverse effects subside spontaneously or with dosage reduction. It is eliminated mainly by hepatic metabolism to inactive metabolites.9% sodium chloride injection Children PO 15–30 mg/kg/d Remarks • Therapeutic serum levels are 50–100 mcg/mL (SI units 350–700 µmol/L) • Note: Dosage ranges are the same for the different formulations. Clonazepam has a long half-life and may require weeks of continued administration to achieve therapeutic serum levels. and complex partial seizures Adults PO 10–15 mg/kg/d. It is 60% absorbed with usual doses. phenytoin equivalent. withdrawal symptoms may appear several days after administration is stopped. • Do not give IV >14 days. 1000–1600 mg.

The drug is well absorbed with oral administration. Levetiracetam (Keppra) is a newer drug approved for treatment of partial seizures. In older adults. To discontinue. drowsiness. Dosage must be reduced with impaired renal function. Lamotrigine is about 55% bound to plasma proteins. It is thought to reduce the release of glutamate. and fatigue. anxiety. adverse effects were similar in adult and pediatric patients and when oxcarbazepine was used alone or with other AEDs. and hyponatremia. Because of the risk of hyponatremia. along with a small amount of unchanged drug. blurred or double vision. The drug inhibits cytochrome P450 2C19 enzymes and induces 3A4 enzymes to influence the metabolism of other drugs metabolized by these enzymes. It inhibits abnormal neuronal firing but does not affect normal neuronal excitability or function. oxcarbazepine increases metabolism of estrogens and may decrease the effectiveness of oral contraceptives and postmenopausal estrogen replacement therapy. either drug may be substituted for the other without tapering the dose of one or gradually increasing the dose of the other. lamotrigine should not be given to children younger than 16 years of age and should be discontinued at the first sign of skin rash in an adult. with peak plasma levels in about 5 hours. Its use has declined with the advent of other AEDs that cause less sedation and cognitive impairment. Skin rash is more likely to occur with concomitant valproic acid therapy. dosage must be substantially reduced. It is chemically unrelated to other AEDs and its mechanism of action is unknown. Phenobarbital is a long-acting barbiturate that is used alone or with another AED (most often phenytoin). emotional lability. ataxia. The drug is not metabolized by the liver and does not affect the hepatic metabolism of other drugs. In clinical trials. paresthesia.CHAPTER 11 ANTISEIZURE DRUGS 189 Lamotrigine (Lamictal) is used with other AEDs for treatment of partial seizures. Phenytoin. levetiracetam has pharmacokinetic and other characteristics that may make it especially useful in clients who require combination antiepileptic drug therapy. about 25% is eliminated unchanged in the urine. pharyngitis. in combination with other AEDs. Common adverse effects include drowsiness. in the brain. headache. and rapid titration rate. carbamazepine. drowsiness. it has a low potential for drug interactions. including phenytoin. If lamotrigine is combined with other AEDs plus valproic acid. the metabolite is 40% protein bound. especially in children. Lamotrigine has little effect on the metabolism of other AEDs. Because a serious skin rash may occur. Several drug–drug interactions may occur with oxcarbazepine. double vision. This rapid attainment of therapeutic effects is especially useful for patients with frequent or severe seizures. drugs that inhibit these enzymes (eg. skin rash. and serum sodium levels should be monitored periodically during maintenance therapy.5 hours. For example. hypotension. Food reduces peak plasma levels by 20% and delays them to 1. amnesia. Valproic acid inhibits those enzymes and thereby slows lamotrigine’s metabolism by approximately 50%. It is approved for both monotherapy and adjunctive (with other AEDs) therapy in adults with partial seizures and for adjunctive therapy only in children. Adverse effects include dizziness. It was well tolerated in clinical trials and the incidence of adverse events was similar to that of placebo. Thus. ataxia. They included cardiac dysrhythmias. Most effects are attributed to an active metabolite produced during first-pass metabolism in the liver. and phenobarbital induce drugmetabolizing enzymes in the liver and accelerate lamotrigine’s metabolism. but it progresses in some clients to a more severe form. the equivalent dose of oxcarbazepine is 50% higher than the carbamazepine dosage. nervousness. cimetidine. dizziness. and weakness. Dosage must be reduced in patients with severe renal impairment (ie. CNS depression and other adverse effects associated with barbiturates may occur. dosage should be tapered over at least 2 weeks. it takes 2 to 3 weeks to reach therapeutic serum levels and 3 to 4 weeks to reach a steady-state concentration. nausea. but does not affect the extent of drug absorption. with peak plasma levels reached in 1. The drug is minimally bound (10%) to plasma proteins and reaches steady-state plasma concentrations after 2 days of twice daily administration. but drug dependence and barbiturate intoxication are unlikely with usual antiepileptic doses. Overall. The metabolite is conjugated with glucuronic acid in the liver and excreted in the urine. It induces drug-metabolizing enzymes in the liver and thereby accelerates the metabolism of most AEDs when given with them. It may resolve if lamotrigine is discontinued. It is metabolized in the liver. creatinine clearance < 30 mL/min). may reduce plasma levels of the active metabolite by about one third. erythromycin) do not significantly affect the elimination of oxcarbazepine or its metabolite. Oxcarbazepine (Trileptal) is a newer drug that is structurally related to carbamazepine. an excitatory neurotransmitter. peak plasma levels occur in about one hour. However. who take drugs with increased potential for drug interactions. In addition. The elimination half-life is 2 hours for oxcarbazepine and 9 hours for the metabolite. Because phenobarbital has a long half-life (50 to 140 hours). Levetiracetam is well and rapidly absorbed with oral administration.5 to 4. the recommended equivalent oxcarbazepine dosage is 20% higher than the carbamazepine dosage. others include decreases in red and white blood cell counts. vomiting. such as Stevens-Johnson syndrome. high lamotrigine starting dose. or who have impaired liver function. Effects on other drugs begin 1 or 2 weeks after phenobarbital therapy is started. For patients receiving carbamazepine or oxcarbazepine. other drugs that induce cytochrome P450 enzymes. oxcarbazepine should be used with caution in clients taking other drugs that decrease serum sodium levels. Some studies indicate that skin reactions occur less often with oxcarbazepine than with carbamazepine. It is metabolized in the liver to an inactive metabolite and eliminated mainly in the urine.5 hours. but other AEDs affect lamotrigine’s metabolism. and rhinitis. It is well absorbed after oral administration. dizziness. . nausea and vomiting. hostility. Most of a dose (66%) is eliminated by the kidneys as unchanged drug.

triamterene. is used with other AEDs in clients with partial seizures. Drugs that induce the cytochrome P450 enzymes (eg. Valproic acid (Depakene) is available in capsules. including the life-threatening Stevens-Johnson syndrome. dizziness. Zonisamide apparently does not induce or inhibit the cytochrome P450 enzymes and therefore has little effect on the metabolism of other drugs. Its elimination half-life is about 63 hours in plasma and >100 hours in red blood cells. phenytoin. peak plasma levels occur in about 45 minutes if taken on an empty stomach and 2. helpful assessment data can be obtained by interviewing the client. It is rapidly absorbed and produces peak plasma levels in about 2 hours after oral administration. Topiramate (Topamax). does not seem to inhibit zonisamide metabolism or increase its halflife. CNS effects (eg. The most common adverse effects are ataxia. Clients with impaired liver function may need smaller doses because the drug is cleared more slowly. Additive CNS depression may occur with alcohol and other CNS depressant drugs. abnormal thinking. There is also a risk of kidney stones. Zonisamide (Zonegran) is chemically a sulfonamide (and contraindicated for use in clients who are allergic to sulfonamides). may act by increasing the effects of GABA and other mechanisms. what parts of the body are involved? Does he or she lose consciousness? Is he or she drowsy and tired afterward? . which can be reduced by increasing dosage gradually. which has a broad spectrum of antiseizure activity. ataxia. which may increase GABA levels in the brain. avoiding concurrent use of topiramate with other drugs associated with renal stone formation or increased urinary pH (eg. However. tiagabine is well absorbed. or what is the frequency of seizures? • Does any particular situation or activity precipitate a seizure? • How does the seizure affect the client? For example. potentially serious adverse effects include hepatotoxicity and pancreatitis. drowsiness. It is not extensively metabolized and is primarily eliminated unchanged through the kidneys. It is metabolized by the cytochrome P450 3A enzymes and perhaps other pathways. The average elimination half-life is about 21 hours. These preparations produce less sedation and cognitive impairment than phenytoin and phenobarbital. It is excreted in the urine as unchanged drug (35%) and metabolites (65%). Dosages of all formulations are expressed in valproic acid equivalents. It is approved for adjunctive treatment of partial seizures and may also be effective for monotherapy and generalized seizures. Interventions to help prevent renal stones include maintaining an adequate fluid intake. GI upset and a serious skin rash may also occur. dosage should be reduced by one half. Divalproex sodium (Depakote) contains equal parts of valproic acid and sodium val- proate and is available as delayed-release tablets and sprinkle capsules. Valproic acid preparations (Depakene. They are primarily metabolized in the liver and metabolites are excreted through the kidneys. Valproic acid preparations are well absorbed after oral administration and produce peak plasma levels in 1 to 4 hours (15 minutes to 2 hours with the syrup). by the cytochrome P450 3A family of enzymes. carbamazepine). which inhibits the cytochrome P450 enzymes. heart failure) or a history of renal stones. It is 40% bound to plasma proteins and also binds extensively to red blood cells. Depacon. Adverse effects include drowsiness. They are also used to treat manic reactions in bipolar disorder and to prevent migraine headaches. dizziness. After oral administration. zonisamide). Some questions and guidelines include the following: • How long has the client had the seizure disorder? • How long has it been since seizure activity occurred. Renal stones may also occur. confusion. administration with cimetidine. nervousness. which is higher in clients with an inadequate fluid intake or who also take topiramate or triamterene. impaired concentration or speech) are the most common adverse effects. The drugs are contraindicated in people who have had hypersensitivity reactions to any of the preparations and people with hepatic disease or impaired hepatic function. and avoiding topiramate in people with conditions requiring fluid restriction (eg. Although they are uncommon. has been observed. Nursing Process Assessment Assess client status in relation to seizure activity and other factors: • If the client has a known seizure disorder and is taking antiseizure drugs.190 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Tiagabine (Gabitril). Depacon is an injectable formulation of valproate. They are thought to enhance the effects of GABA in the brain. Skin rash. confusion. For clients with a creatinine clearance below 70 mL/minute. The elimination half-life is 4 to 7 hours in clients receiving enzymeinducing AEDs (eg. over several weeks. It is thought to act by inhibiting the entry of sodium and calcium ions into nerve cells. Clients with impaired renal function may require lower doses or a slower titration schedule. It is highly protein bound (96%) and is extensively metabolized in the liver. Zonisamide is well absorbed with oral administration and produces peak plasma levels in 2 to 6 hours. and nausea. Only 1% of the drug is excreted unchanged in the urine and the metabolites are excreted in urine and feces. and steady-state concentrations are reached in about 4 days with normal renal function. It is 20% bound to plasma proteins. They are highly bound (90%) to plasma proteins. and fatigue. carbamazepine. sodium valproate is a syrup formulation. drowsiness. Depakote) are chemically unrelated to other AEDs. phenytoin) increase the metabolism of zonisamide and reduce its half-life.5 hours if taken with food.

and others. and withdrawal from CNS depressants. as well as those taken regularly or periodically. especially those that impair safety. Most of these seizures. and the person starts responding and regaining normal skin color.CHAPTER 11 ANTISEIZURE DRUGS 191 • Which antiseizure drugs are taken? How do they affect the client? How long has the client taken the drugs? Is the currently ordered dosage the same as what the client has been taking? Does the client usually take the drugs as prescribed. compliance or rejection of drug therapy. The goal is to avoid unrealistic expectations and excessive frustration while drugs and dosages are being changed in an effort to determine the best regimen for the client. fractures may result. Check reports of serum drug levels for abnormal values. and the importance of complying with prescribed drug therapy with the client and family members. • What is the client’s attitude toward the seizure disorder? Clues to attitude may include terminology. especially status epilepticus. such as loss of consciousness and loss of bowel or bladder control. seizure disorders may develop with brain surgery. head injury. hypoglycemia. . Risk factors include recent changes in antiseizure drug therapy. such as alcohol and barbiturates. if needed. especially around the neck and chest. abnormal movements. however. confusion • Risk for Injury: Seizure activity or drug toxicity • Noncompliance: Underuse of medications Planning/Goals The client will: • • • • • Take medications as prescribed Experience control of seizures Avoid serious adverse drug effects Verbalize knowledge of the disease process and treatment regimen • Avoid discontinuing antiseizure medications abruptly • Keep follow-up appointments with health care providers Evaluation • Interview and observe for decrease in or absence of seizure activity. This information is necessary because many drugs interact with antiseizure drugs to decrease seizure control or increase drug toxicity. • Help the client identify conditions under which seizures are likely to occur. Discuss social and economic factors that promote or prevent compliance. or has sustained an injury. has trouble breathing or continued cyanosis. and a physician should be notified immediately. dizziness. increasing exercise. Discuss the seizure disorder. • Loosening tight clothing. hypoxia. are identified. reducing alcohol and caffeine intake. use of drugs known to cause seizures. drug overdosage (CNS stimulants. Identify risk factors for seizure disorders. may include ingestion of alcoholic beverages or stimulant drugs. and loss of consciousness that characterize a generalized tonic-clonic seizure can be quite alarming to witnesses. such as flashing lights and loud noises. Involve the client in decision making when possible. specific characteristics of abnormal movements or behavior. subside within 3 or 4 minutes. duration. If the person has one seizure after another (status epilepticus). or does he or she find it difficult to do so? • What other drugs are taken? This includes both prescription and nonprescription drugs. concomitant events. Interventions Use measures to minimize seizure activity. Assist the client in planning how to get enough rest and exercise and eat a balanced diet. chronic alcohol ingestion. In people without previous seizure activity. and postseizure behavior. such as amphetamines or cocaine. Identification of precipitating factors is important because lifestyle changes (reducing stress. • Interview and observe for avoidance of adverse drug effects. note the location (localized or generalized). The cyanosis. improving sleep and diet) and treatment of existing disorders can reduce the frequency of seizures. further care is needed. Protect a client experiencing a generalized tonic-clonic seizure by: • Placing a pillow or piece of clothing under the head if injury could be sustained from the ground or floor. severe physical or emotional stress. • Not restraining the client’s movements. • • • • • • • • • • Nursing Diagnoses • Ineffective Coping related to denial of the disease process and need for long-term drug therapy • Deficient Knowledge: Disease process • Deficient Knowledge: Drug effects • Risk for Injury: Trauma related to ataxia. to be avoided or decreased when possible. check laboratory reports of serum drug levels for therapeutic ranges or evidence of underdosing or overdosing. willingness or reluctance to discuss the seizure disorder. Guidelines include the following: • When available. • Turning the client to one side so that accumulated secretions can drain from the mouth and throat when convulsive movements stop. Inform the client and family that seizure control is not gained immediately when drug therapy is started. or local anesthetics. the plan for treatment. These precipitating factors. try to prevent or minimize their occurrence. To observe and record seizure activity accurately. and sensory stimuli. such as lidocaine). Assess for risk of status epilepticus. fever. When risk factors for seizures. to promote respiration. and infection.

✔ There are differences in formulations that may upset seizure control and cause adverse effects. Severe. 2. ✔ ✔ ✔ ✔ ✔ . Phenytoin may inhibit the release of insulin and increase blood sugar. ✔ Do not take any other drugs that cause drowsiness. including over-the-counter antihistamines and sleep aids. This will prevent or decrease nausea. and if you become pregnant. ✔ When taking generic phenytoin or the Dilantin brand of phenytoin: 1. or other emergency situation. yellowish skin or eyes. ✔ Carry identification. mix it thoroughly immediately before use and measure it with a calibrated medicine cup or a measuring teaspoon. Swallow tablets or capsules of valproic acid (Depakene or Depakote) whole. At the same time. Self-administration ✔ Take most antiseizure medications with food or a full glass of fluid. excessive drowsiness. mix it thoroughly immediately before use. or vitamin K. ✔ Do not drive a car. ✔ Do not take other drugs without the physician’s knowledge and inform any other physician or dentist about taking antiseizure medications. topiramate (Topamax). vitamin D. 6. swollen glands. ✔ Notify your physician if you are breast-feeding or intend to breast-feed during therapy. oxcarbazepine (Trileptal). The syrup formulation may be diluted in water or milk but should not be mixed in carbonated beverages. such as a MedicAlert device. Excessive drowsiness. Measure it with the syringe supplied by the manufacturer and squirt the medication directly into the mouth. wear protective clothing and sunscreen. unusual bleeding or bruising. Levetiracetam (Keppra). Do not use regular teaspoons because they hold varying amounts of medication. swollen or tender gums. additional doses must not be taken because of increased risks of serious adverse reactions. sore throat. joint pain. Oxcarbazepine (Trileptal) decreases the effectiveness of oral contraceptive drugs. bleeding. If you are taking phenytoin liquid suspension or giving it to a child. Brush and floss your teeth and have regular dental care to prevent or delay a gum disorder called gingival hyperplasia. and zonisamide (Zonegran) may be taken with or without food. There are many potential drug interactions in which the effects of the antiseizure drug or other drugs may be altered when drugs are given concomitantly. other adverse effects) associated with an antiseizure medication with the prescribing physician or other health care professional. which are adverse reactions to most of these drugs. and gastric distress. Taking valproic acid at bedtime may reduce dizziness and drowsiness. with the name and dose of the medication being taken. persistent headache. These supplements may help to prevent some adverse effects of phenytoin. seizures may occur if the drugs are stopped abruptly. you may need to check your blood sugar more often or take a higher dose of your antidiabetic medication. decreased physical coordination. severe nausea and vomiting. or vice versa. ✔ Discuss any problems (eg. It is helpful to write the date opened and the expiration date on the container. or perform other activities requiring physical and mental alertness when drowsy from antiseizure medications. notify the physician immediately if a skin rash or decreased seizure control develops. If you have diabetes. vomiting. accidental injury. This is extremely important. 4. ✔ Notify your physician if you become pregnant or intend to become pregnant during therapy. chewing or crushing may cause irritation of the mouth and throat. and decreased mental alertness increase the likelihood of injury. the regular capsule should not be opened and the tablet should not be crushed for administration. Lamotrigine may cause photosensitivity. If you are taking oxcarbazepine liquid suspension or giving it to a child. 5. without discussing with the prescribing physician. operate machinery. Adjusting dosage or time of administration may relieve the problems. even life-threatening. unexplained fever. Do not switch from a generic to Dilantin. calcium. 3. If taking lamotrigine. The sprinkle capsule may be opened and the contents sprinkled on soft food for administration. ✔ Do not suddenly stop taking any antiseizure medication. Ask your physician if you should take (or give a child) supplements of folic acid. or any indication of infection or bleeding.192 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM CLIENT TEACHING GUIDELINES Antiseizure Medications General Considerations ✔ Take the medications as prescribed. Notify your physician or another health care professional if you develop a skin rash. This is necessary for rapid and appropriate treatment in the event of a seizure. With valproic acid. When outdoors. These drugs must be taken regularly to maintain blood levels adequate to control seizure activity. seizure activity. Store the suspension at room temperature and use the bottle within 7 weeks or discard the amount remaining.

In general. Hammerly experiences a generalized seizure. The goal is to control seizure activity with minimal adverse drug effects. ethosuximide ($105 to $158). phenytoin. This is not necessary when substituting oxcarbazepine for carbamazepine or vice versa. and tiagabine. Dosage forms may increase seizure control. ethosuximide is the drug of choice. drug may be added. For mixed seizures. The nurse holds all medications. Fewer and milder adverse effects can greatly increase a client’s willingness to 4. For example. poor compliance. valproic acid. therapy must be individualized. phenobarbital ($2 to $5). treatment with a single AED is sufficient to meet this goal. which depend on manufacturers’ wholesale prices and pharmacies’ markups as well as prescribed dose amounts and other factors. may vary among pharmacies and change over time. If effective in controlling seizures. in adequate dosage. topiramate. lamotrigine ($196 to $289). Pregnancy risk. and zonisamide ($100 to $201). Although the newer drugs are generally effective and better tolerated than older agents. choosing less expensive drug therapy regimens. Hammerly’s surgery is delayed so you decide to help her with her shower. and usually greater client compliance. Drug Selection 1. 6. Most of these agents are approved for combination therapy with other AEDs in clients whose seizures are not adequately controlled with a single drug. monotherapy has the advantages of fewer adverse drug effects. Sexually active adolescent girls and women of childbearing potential who require an AED must be evaluated and monitored very closely because . If the first drug. A single drug (monotherapy) is recommended when possible. topiramate ($88 to $354). the clinician may need to reassess the client for type of seizure. the second drug should be added and allowed to reach therapeutic blood levels before the first drug is gradually decreased in dosage and discontinued. phenytoin ($26 to $35). and compliance with the prescribed drug therapy regimen. medical conditions or drug– drug interactions that aggravate the seizure disorder or decrease the effectiveness of AEDs. fails to control seizures or causes unacceptable adverse effects. they are also quite expensive. oxcarbazepine ($97 to $358). for uninsured clients. The use of carbamazepine and valproic acid increased largely because they cause less sedation and cognitive and psychomotor impairment than phenobarbital and phenytoin. In most clients. then another agent should be tried as monotherapy. Adverse drug effects may be the deciding factor in choosing an AED because most types of seizures can be treated effectively by a variety of drugs. AEDs with activity against both partial-onset and generalized seizures include lamotrigine. 3. and zonisamide. Most practitioners recommend sequential trials of two to three agents as monotherapy before considering combination therapy. She is NPO after midnight. and higher costs. Drugs considered most useful for partial seizures include carbamazepine. oxcarbazepine. Oxcarbazepine is approved for monotherapy of partial seizures. Ms. In the morning. However. and valproate ($80 to $280). extended release or long-acting dosage forms can maintain more consistent serum drug levels and decrease frequency of administration. Hammerly is admitted to your unit for neurosurgery in the morning. prescribers can encourage compliance by choosing drugs that are covered by clients’ insurance plans or. tiagabine ($99 to $190). levetiracetam ($105 to $315). the following list of costs per month allow comparisons among AEDs and may be useful in clinical practice. combination therapy is associated with more severe adverse effects. PRINCIPLES OF THERAPY Therapeutic Goal Drug therapy is the main treatment of epilepsy for clients of all ages. Guidelines for newer drugs are evolving as research studies are done and clinical experience with their use increases. In 20% to 30% of clients. Costs. fewer drug–drug interactions. Most of the newer AEDs reportedly cause fewer adverse effects and are better tolerated than the older drugs although they may also cause potentially serious adverse effects. Type of seizure is a major factor. When possible. Therefore. clonazepam and valproate are also effective. some of the other drugs are also thought to be effective as monotherapy. While showering. however. 2. a second. Costs of newer drugs are gabapentin ($139 to $354). levetiracetam. Monotherapy versus combination therapy. although they may cause other potentially serious adverse effects. two or more AEDs are required. Most of the AEDs are available in oral tablets or capsules. lower costs. To meet this goal.CHAPTER 11 ANTISEIZURE DRUGS 193 How Can You Avoid This Medication Error? Ms. phenobarbital. a few are available as oral liquids or injectable solutions. Costs of older drugs are carbemazepine ($54 to $81). comply with the prescribed regimen and attain seizure control. Ms. When monotherapy is ineffective. and compliance. interactions between AEDs. If combination therapy is ineffective. 5. gabapentin. because the drugs are similar. For absence seizures. which is usually taken at midnight and 6 AM. an accurate diagnosis is essential before drug therapy is started. Cost should be considered because this may be a major factor in client compliance. When substituting one AED for another. including her antiseizure medication. In general. a combination of drugs is usually necessary. and sometimes a third. client convenience.

Smaller doses are usually required when liver disease is present and when multiple drugs are being given. 2. . and how the drugs should be discontinued. Other causes include incorrect diagnosis of the type of seizure. aspartate aminotransferase) be performed before drug therapy starts and periodically thereafter. For most patients. 3. When drug therapy fails to control seizures. For this reason. Nursing Notes: Apply Your Knowledge You are a nurse working in a clinic. and smaller doses of lamotrigine must be given when combined with valproic acid and another AED. the timing of blood samples in relation to drug administration is important. Then. or adverse drug effects. studies indicate that medications can be stopped in approximately two thirds of clients whose epilepsy is completely controlled with drug therapy. In addition. The first drug is usually stopped when therapeutic effects or therapeutic serum drug levels of the second drug are attained. bilirubin. serum protein. usually after a seizure-free period of at least 2 years. Additional causes may include drug overdoses (eg. to assess for drug malabsorption or client noncompliance. the same total daily dosage (in PE) may be given IV or IM. there are several possible causes. Although opinions differ about whether. Abruptly stopping an AED may exacerbate seizures or cause status epilepticus. and emotional stress. For routine monitoring. before the first daily dose of an AED. inadequate drug dosage. When one AED is being substituted for another. the equivalent oxcarbazepine dosage is 50% higher than the carbamazepine dosage. to decrease adverse effects. When fosphenytoin is substituted for oral phenytoin.194 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM all of the drugs are considered teratogenic. His Dilantin level is drawn and is 19 mcg/mL. comes into the clinic complaining of problems with poor coordination and fatigue. 5. larger doses are needed for a single drug than for multiple drugs. 1. doses are gradually increased until seizures are controlled or adverse effects occur. The effectiveness of drug therapy is evaluated primarily by client response in terms of therapeutic or adverse effects. or kidney disorders. and too-frequent changes or premature withdrawal of drugs. theophylline) and severe electrolyte imbalances (eg. When switching between agents in older adults. This helps to document blood levels associated with particular drug dosages. for people with a large body mass (assuming normal liver and kidney function). hyponatremia) or use of alcohol or recreational drugs. and topiramate must be given in the presence of renal impairment. Several antiseizure drugs have the potential for causing blood. platelet count) and liver function tests (eg. if treatment is started too aggressively. an epileptic for the last 10 years. 3. To be useful. the recommended equivalent oxcarbazepine dosage is 20% higher than the carbamazepine dosage. surgery. How should you proceed? Drug Dosage The dosage of most drugs is determined empirically by observation of seizure control and adverse effects. initial doses are relatively low. it is usually recommended that baseline blood studies (complete blood count. His seizures have been well controlled on phenytoin (Dilantin) 300 mg hs. In general. use of the wrong drug for the type of seizure. When an AED is being discontinued. In other words. especially when multiple AEDs are being given. to assess and document therapeutic failures. liver. serum drug levels must be interpreted in relation to clinical responses because there are wide variations among clients receiving similar doses. its dosage should always be tapered gradually. Periodic measurements of serum drug levels are recommended. and to evaluate possible drug-related adverse effects. Duration and Discontinuation of Therapy Antiseizure drug therapy may be discontinued for some clients. doses may be lowered to the minimum effective level. either agent may be substituted for the other without gradual reduction or titration of the dose. to guide dosage adjustments. 2. Usually. 4. seizure control. Smaller doses of gabapentin. blood samples should generally be obtained in the morning. Adverse effects are more likely to occur during initiation of treatment and. and in cases involving trauma. doses should not be increased or decreased solely to maintain a certain serum drug level. levetiracetam. For patients receiving carbamazepine or oxcarbazepine therapy. Mr. dosage of the one being added is gradually increased while the one being discontinued is gradually decreased. clients may be unwilling to continue a particular medication even if doses are reduced in amount or frequency of administration. Monitoring Antiepileptic Drug Therapy 1. His speech also seems somewhat slurred. probably owing to differences in hepatic metabolism. A common one is the client’s failure to take the antiseizure drug as prescribed. For most drugs. usually over 1 to 3 months. when. Eng. infants exposed to one AED have a significantly higher risk of birth defects than those not exposed and infants exposed to two or more AEDs have a significantly higher risk than those exposed to one AED.

mexilitene. Few interactions have been reported with the newer drugs. phenytoin decreases therapeutic effects. Hemodialysis is effective in removing drugs that are poorly bound to plasma proteins and that are excreted mainly or partly by the kidneys (eg. respiratory depression. Topiramate decreases effects of digoxin and oral contraceptives. levetiracetam. methadone. adrenal corticosteroids. or changing dosage must be done gradually over 2 to 3 months for each drug and with close medical supervision because sudden withdrawal or dosage decreases may cause status epilepticus. There are no specific antidotes and treatment is symptomatic and supportive (ie. In infants and children. personnel and supplies for emergency resuscitation must be readily available. longer-acting drug is given. antipsychotic drugs (eg. pupillary reflexes. The rapid rate of drug elimination persists until approximately 6 years of age. dopamine. and theophylline. An endotracheal tube should be inserted prior to lavage. doxycycline. Oxcarbazepine decreases effectiveness of felodipine and oral contraceptives (a barrier type of contraception is recommended during oxcarbazepine therapy). the consequence of decreasing the effects of sulfonylureas may be greater difficulty in controlling blood sugar levels in diabetic clients who require both drugs. levonorgestrel).CHAPTER 11 ANTISEIZURE DRUGS 195 Advantages of discontinuation include avoiding adverse drug effects and decreasing costs. haloperidol). electrocardiogram (ECG). Zonisamide interacts with other AEDs but no interactions have been reported with non-AEDs. then decreases until it stabilizes around the adult rate by age 10 to 14 years. oral antidiabetic agents (eg. oral contraceptives. Further treatments are based on the patient’s response to these medications. Effects of Antiepileptic Drugs on Non-Antiepileptic Drugs Antiepileptic drugs may have clinically significant interactions with many non-AEDs. changing drugs. gastric lavage and activated charcoal. level of consciousness. They may also decrease the effects of numerous other drugs. valproate). Even if drugs cannot be stopped completely. doxycycline. Drug Therapy for Status Epilepticus An IV benzodiazepine (eg. cyclosporine. Fatalities have been reported with most antiseizure drugs. if indicated. Toxicity of Antiseizure Drugs: Recognition and Management Signs and symptoms of overdose and toxicity are usually extensions of known adverse effects. Vital signs. In some cases. a serum drug level is indicated for those drugs with established therapeutic ranges. The consequence of increasing metabolism of oral contraceptives may be unintended pregnancy. Because the drugs depress the . such as IV phenytoin (20 mg/kg at 50 mg/minute) or fosphenytoin (20 mg/kg phenytoin equivalents at 150 mg/ minute). gabapentin. Severe overdoses disturb vital functions (eg. The effects on acetaminophen are the same as those of phenytoin (see above). impaired consciousness and possible coma. CNS and cause drowsiness. oral drugs are rapidly absorbed and have short half-lives. felodipine. Activated charcoal is not effective in adsorbing topiramate and is not recommended for topiramate overdose. Phenytoin reduces the effects of cardiovascular drugs (eg. Rates of metabolism and excretion also are increased. With acetaminophen. to prevent aspiration). but may increase the risk of hepatotoxicity by accelerating production of the metabolite that damages the liver. Consequently. If an antiseizure drug is necessary during the first 7 to 10 days of life. Metabolism and excretion also are delayed during the first 2 weeks of life. More interactions with these drugs may be observed with longer clinical use. sulfonylureas). furosemide. quinidine). topiramate. their combination with any other CNS depressant drugs may cause excessive sedation and other adverse CNS effects. amiodarone. disadvantages include recurrence of seizures. Carbamazepine reduces the effects of tricyclic antidepressants. lorazepam 0. Discontinuing drugs. to prevent absorption of additional drug. oral anticoagulants. phenothiazines. children require higher doses per kilogram of body weight than adults. Enzyme induction means the affected drugs are metabolized and eliminated more quickly. but rates become more rapid than those of adults by 2 to 3 months of age. larger doses of the affected drugs are needed to achieve therapeutic effects. with possible status epilepticus. Use in Children Oral drugs are absorbed slowly and inefficiently in newborns. levodopa. disopyramide. bupropion. oral contraceptives. However. AEDs must be used cautiously to avoid excessive sedation and interference with learning and social development. periodic attempts to decrease the number or dosage of drugs are probably desirable to minimize adverse reactions. cardiovascular problems such as dysrhythmias and hypotension) and are life-threatening. Levetiracetam does not induce or inhibit hepatic metabolism of drugs and risks of interactions are minimal. CNS depression with confusion. female sex hormones (estrogens. digoxin. IM phenobarbital is effective. and haloperidol. Because there is a risk of significant respiratory depression with IV benzodiazepines. mainly by inducing drug-metabolizing enzymes in the liver. seizures often recur unless the benzodiazepine is repeated or another. and urine output should be monitored. Only one drug should be reduced in dosage or gradually discontinued at a time. If toxicity is suspected. This produces therapeutic serum drug levels earlier in children than in adults.1 mg/kg at 2 mg/ minute) is the drug of choice for rapid control of tonic-clonic seizures.

With renal impairment. including status epilepticus. oxcarbazepine. the rate of metabolism is similar to that in adults after 8 years. and drowsiness that may occur with most AEDs. and injuries due to falls. or cardiac dysrhythmias. take multiple drugs. ataxia. Phenytoin therapy can best be monitored by measuring free serum phenytoin concentrations. Use in Older Adults Seizure disorders commonly occur in older adults and require drug therapy. phenytoin. lamotrigine. As a result. there is little information about their effects in children. older adults may develop a tremor that is difficult to diagnose because of its gradual onset and similarity to the tremor occurring with Parkinson’s disease. In some clients. The occurrence of nystagmus (abnormal movements of the eyeball) indicates phenytoin toxicity. renal failure. active drug is higher than in clients with normal renal function. Zonisamide should not be given to patients with renal failure and should be discontinued in patients who develop acute renal failure or increased serum creatinine and blood urea nitrogen during therapy. nobarbital in clients with severe renal impairment requires markedly reduced dosage. slow titration to desired doses. It should be used with caution in the presence of hepatic impairment. Older adults with preexisting heart disease should have a thorough cardiac evaluation before starting carbamazepine therapy. a history of long-term AED therapy may be a risk factor for seizures. Several studies indicated that oxcarbazepine is effective in monotherapy and combination therapy. close monitoring of plasma drug levels. tremor) have been observed in clients with mild and moderate hepatic insufficiency. Most of the drugs (eg. and kidney function are indicated. with subsequent risks of dizziness. with carbamazepine. Doses may need to be reduced or given at less frequent intervals. and frequent observation for toxic effects. increased elimination half-life. Increased plasma levels of unbound tiagabine. Elimination of tiagabine is not significantly affected by renal insufficiency. Topiramate may also be cleared more slowly even though it is eliminated mainly through the kidneys and does not undergo significant hepatic metabolism. especially if they have underlying heart disease. furosemide. Using controlledrelease formulations. and have decreases in protein binding and liver and kidney function. In addition. or zonisamide. dizziness.196 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM With the newer AEDs. and topiramate) are approved for use in children. levetiracetam. they may develop hyponatremia. dizziness. continuing an AED may complicate drug therapy of other conditions because of adverse Use in Renal Impairment Phenytoin is often used to prevent or treat seizure disorders in seriously ill clients. oxcarbazepine. or hemodialysis. Use in Critical Illness Phenytoin is often used to prevent or treat seizure disorders in critically ill clients. With valproic acid. the drug should be reduced in dosage or discontinued until serum levels decrease. a low total phenytoin level may still be therapeutic and a dosage increase is not indicated. when available. For example. Dosage of oxcarbazepine should be decreased by 50% in patients with creatinine clearance <30 mL/minute. The tremor is often dose-related and reverses when the drug is reduced in dosage or discontinued. if the drug is stopped abruptly. tiagabine. Valproic acid is a hepatotoxic drug and contraindicated for use in hepatic impairment. levetiracetam and zonisamide are not approved for use in children. frequent assessment of clients for adverse effects and periodic monitoring of serum drug levels. oxcarbazepine. Use in Hepatic Impairment Most AEDs are metabolized in the liver and may accumulate in the presence of liver disease or impaired function. especially if they also take sodiumlosing diuretics (eg. older adults are at high risk of adverse drug effects and adverse drug–drug interactions with AEDs. confusion. reduced levels of serum albumin may increase the active portion of highly protein bound AEDs (eg. gabapentin. The use of phe- . impaired coordination. clients with severe illnesses may metabolize the drug more slowly and therefore experience toxicity. In general. small initial doses. Because phenytoin is extensively metabolized in the liver. to minimize peak plasma concentrations. valproic acid) and increase risks for adverse effects even when total serum drug concentrations are normal. In addition to the ataxia. hydrochlorothiazide). The drugs should be used cautiously. older adults are also more likely to develop some adverse effects associated with specific drugs. and dose adjustment for renal dysfunction is not necessary. liver function. topiramate. decreased elimination by the liver and kidneys may lead to drug accumulation. and small maintenance doses are needed. and zonisamide must be given in the presence of renal impairment because these drugs are eliminated primarily through the kidneys. drowsiness. These effects may also occur with oxcarbazepine. For clients in critical care units for other disorders. and increased frequency of neurologic adverse effects (eg. Most of these potential problems can be averted or minimized by using AEDs very cautiously in older adults. Oxcarbazepine is metabolized faster in children younger than 8 years of age. Older adults often have multiple medical conditions. Smaller doses of gabapentin. including those with head injuries. may also be helpful. with relatively few and mild adverse effects. At the same time. For example. Similarly. protein binding is decreased and the amount of free. No dosage adjustment is indicated with levetiracetam. but laboratories usually report the total serum drug concentration. Tiagabine is cleared more slowly in clients with liver impairment. Renal stones have been reported with topiramate and zonisamide.

the liquid vehicle will be given initially. Shaking the container is necessary to distribute drug particles in the liquid vehicle. Give most oral antiseizure drugs after meals or with a full glass of water or other fluid. a drug often used to treat hypotension and shock in critical care units. phenytoin decreases ventricular automaticity and should not be used in critically ill clients with sinus bradycardia or heart block. and characteristics of seizures can be very helpful). particles of drug are suspended in water or other liquid. Taking the drugs with food or fluid helps decrease gastrointestinal side effects. hypotension. With long-term use of the drugs. In suspensions. ensuring that the client keeps appointments for serum drug levels and follow-up care. The dose is expressed in phenytoin equivalents (PE. A precipitate occurs if mixing is attempted. To give phenytoin: (1) Shake oral suspensions of the drug vigorously before pouring and always use the same measuring equipment. underdosage will occur at first. and encouraging compliance with the prescribed regimen. NURSING ACTIONS NURSING ACTIONS Antiseizure Drugs RATIONALE/EXPLANATION 1. d. To maintain therapeutic blood levels of drugs Most antiseizure drugs cause some gastric irritation. duration. On standing. interviewing the family about the occurrence of seizures (a log of date. and the risks of serious toxicity are greatly increased. a few weeks may be required to titrate the dosage and determine whether the chosen drug is effective in controlling seizures. Using the same measuring container ensures consistent dosage. or vomiting. (2) Do not mix parenteral phenytoin in the same syringe with any other drug. topiramate. especially with changes in drugs or dosages.9% NaCl) and administer over approximately 30–60 minutes. phenytoin decreases the effects of dopamine. Slow administration and dilution decrease local venous irritation from the highly alkaline drug solution. For example. Rapid administration must be avoided because it may produce myocardial depression. then flush the IV line with normal saline or dilute in 50–100 mL of normal saline (0. Administer accurately a. (3) Give phenytoin as an undiluted (IV) bolus injection at a rate not exceeding 50 mg/min. the primary IV solution must be normal saline or the line must be flushed with normal saline before and after administration of phenytoin. Regular household teaspoons and tablespoons used for eating and serving are not acceptable because sizes vary widely. In addition. An in-line filter is recommended. oxcarbazepine. Calibrated medication cups or measuring teaspoons or tablespoons are acceptable. the nurse may need to review the potential loss of seizure control and potential for status epilepticus. and even cardiac arrest. Home Care The home care nurse must work with clients and family members to implement and monitor AED therapy. Phenytoin cannot be diluted or given in IV fluids other than normal saline because it precipitates within minutes. (continued ) . drug particles settle to the bottom of the container. fosphenytoin 50 mg PE = phenytoin 50 mg). nausea. Phenytoin solution is highly alkaline (pH approximately 12) and physically incompatible with other drugs. With any evidence that the client is not taking medication as directed. and the concentrated drug will be given later. c. The nurse can play an important role by clinical assessment of the client. cardiac arrhythmias. and zonisamide may be taken with or without food. time. Give on a regular schedule about the same time each day. Overdosage will follow. If the contents are not mixed well every time a dose is given. That is. If “piggybacked” into a primary IV line.CHAPTER 11 ANTISEIZURE DRUGS 197 effects and potential drug–drug interactions. and little if any therapeutic benefit will result. levetiracetam. To give IV fosphenytoin: (1) Check the physician’s order and the drug concentration carefully. b. the nurse must monitor the client for therapeutic and adverse drug effects. When an AED is started.

About 25–30% of patients with allergic reactions to carbamazepine are likely to be allergic to oxcarbazepine. Hypocalcemia (continued ) . Also check expiration date. When the drug is given to stop an acute convulsive seizure.198 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM NURSING ACTIONS (2) Dilute the dose in 5% dextrose or 0. These common effects of oral drugs can be reduced by taking the drugs with food or a full glass of water. Dilution and tube irrigation decrease such adherence. Gastrointestinal effects—anorexia. f. IV lorazepam is the drug of choice for controlling an acute convulsion. vomiting c. For accurate measurement and a reminder that the suspension is given orally only. Some are mild. especially in children. Optimum therapeutic benefits of phenytoin occur approximately 7–10 days after drug therapy is started. jaundice. Observe for adverse effects a. such as status epilepticus. is given IV to control acute seizures. Central nervous system (CNS) effects—ataxia. These effects are common. diluting with 4 mL yields the maximum concentration of 25 mg PE/mL. which may progress to megaloblastic anemia. abnormal liver function test results g. RATIONALE/EXPLANATION The drug is preferably diluted in the pharmacy and labeled with the concentration and duration of the infusion. Absorption is slow and decreased. agranulocytosis e. This is not likely to be a significant adverse reaction except when a depressant drug. Observe for therapeutic effects a. Therapeutic effects begin later with antiseizure drugs than with most other drug groups because the antiseizure drugs have relatively long half-lives. exfoliative dermatitis. dizziness. The other disorders indicate bone marrow depression and are potentially life threatening. dilute with an equal amount of water. and rinse the NG tube before and after administration. StevensJohnson syndrome (a severe reaction accompanied by headache. urticaria. nausea. but may infrequently occur with most other antiseizure drugs. such as lorazepam. respiratory depression can be minimized by avoiding overdosage and rapid administration. and other symptoms in addition to skin lesions) d. drowsiness. Gingival hyperplasia h. double vision b. Most antiseizure drugs decrease blood levels of folic acid. possibly because of drug adherence to the NG tube. 3. arthralgia. e. Hypersensitivity reactions—often manifested by skin disorders such as rash. use the 10-mL oral dosing syringe provided by the manufacturer with each bottle.9% sodium chloride solution to a concentration of 1. leukopenia. 2. These skin reactions are usually sufficient reason to discontinue the drug. When the drug is given on a long-term basis to prevent seizures. and fatal hepatotoxicity has been reported with valproic acid. Respiratory depression f. thrombocytopenia. seizure activity usually slows or stops within a few minutes. The suspension is stored at room temperature and must be used within 7 weeks after opening the bottle. Occurs often with phenytoin. To avoid error (3) Consult a pharmacist or the manufacturer’s literature if any aspect of the dose or instructions for administration are unclear. Blood dyscrasias—anemia.9% sodium chloride and infused in approximately 10 min at the maximal recommended rate. Even then. Hepatic damage may occur with phenytoin. especially during the first week or two of drug therapy. They do not usually occur with phenytoin. some are potentially serious but rare. These may occur with almost all the antiseizure drugs. For a 100-mg PE dose. It may be prevented or delayed by vigorous oral hygiene. Liver damage—hepatitis symptoms.5 mg PE/mL to 25 mg PE/mL and infuse no faster than 150 mg PE/min. A 1-g loading dose could be added to 50 mL of 0. observe for a decrease in or absence of seizure activity. May occur when antiseizure drugs are taken in high doses and over long periods b. To give oxcarbazepine suspension. To give carbamazepine and phenytoin suspensions by nasogastric (NG) feeding tube. this amount could be infused in about 1 min at the maximal recommended rate.

Valproic acid inhibits an epoxide hydrolase enzyme and causes an active metabolite to accumulate. diltiazem. These drugs may lower the seizure threshold and precipitate seizures. opioid analgesics. Kidney stones 4. rifampin. clarithromycin. These drugs increase phenytoin toxicity by inhibiting hepatic metabolism of phenytoin or by displacing it from plasma proteinbinding sites. Drugs that increase effects of antiseizure drugs: (1) CNS depressants—alcohol. antineoplastics. Still. time of administration. paroxetine. and other enzyme inducers c. Phenytoin and phenobarbital have complex interactions with unpredictable effects. Additional drugs that alter effects of carbamazepine: (1) Cimetidine. benzodiazepines. and verapamil increase effects. benzodiazepines. nausea. folic acid. omeprazole. chlorpheniramine. fluconazole. to increase therapeutic effects. Hyponatremia RATIONALE/EXPLANATION May occur with carbamazepine and oxcarbazepine. Pancreatitis l. Most of these drugs inhibit the cytochrome P450 enzymes (1A2. Lymphadenopathy resembling malignant lymphoma k. and vomiting. . sertraline. This reaction has occurred with several antiseizure drugs. especially if taken concurrently with sodium-losing diuretics (eg. amiodarone. Usually transient and levels return to normal with fluid restriction or dose reduction. and trimethoprim increase effects. isoniazid. isoniazid. 2C8. Inadequate fluid intake or concurrent administration of triamterene may increase risk. cimetidine. (2) Alcohol (chronic ingestion). Additive CNS depression Additive or synergistic effects. Observe for drug interactions a. and/or 3A4 groups) that normally metabolize carbamazepine. Additional drugs that alter effects of phenytoin and fosphenytoin: (1) Alcohol (acute ingestion). These drugs decrease effects of phenytoin by decreasing absorption. sucralfate. Dosage of antiseizure drugs may need to be increased. and other factors. Drugs that decrease effects of antiseizure drugs: (1) Tricyclic antidepressants. fluoxetine. Phenobarbital apparently decreases serum levels of phenytoin and perhaps its half-life. its interaction with phenytoin differs. erythromycin. or by unknown mechanisms. route. The interaction apparently varies with dosage. and theophylline decrease effects. the anticonvulsant effects of the two drugs together are greater than those of either drug given alone. The drugs are often given in combination.and longterm therapy with valproic acid. the degree of liver enzyme induction already present. Probably the most important clinical implication is that close observation of the client is necessary when either drug is being added or withdrawn. Life-threatening pancreatitis has occurred after short. antipsychotic drugs (2) Carbemazepine. Thus. May occur with topiramate and zonisamide. metronidazole. thereby increasing blood levels of carbamazepine. most often with phenytoin. hydrochlorothiazide). (continued ) d. (3) Phenobarbital has variable interactions with phenytoin. whether a significant interaction will occur in a client is unpredictable. Although phenobarbital induces drug metabolism in the liver and may increase the rate of metabolism of other anticonvulsant drugs. Patients should be monitored for the development of acute abdominal pain. accelerating metabolism. j. phenytoin.CHAPTER 11 ANTISEIZURE DRUGS 199 NURSING ACTIONS i. miconazole. pyridoxine. Toxicity may result even if carbamazepine blood levels are at therapeutic concentrations. furosemide. These drugs inhibit themselves and other antiseizure drugs by activating liver enzymes and accelerating the rate of drug metabolism. sedatives (2) Most other antiseizure drugs b. valproic acid. allopurinol. antacids. sedating antihistamines.

200 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM NURSING ACTIONS (2) Alcohol. . (2) Carbamazepine. Review and Application Exercises 1. and how can they be minimized? 4. These drugs induce drug-metabolizing enzymes in the liver and thereby increase the metabolism and hasten the elimination of oxcarbazepine. Inhibits drug-metabolizing enzymes. discussed in Chapter 8. Reduce absorption of gabapentin. What are the advantages and disadvantages of treatment with a single drug and of treatment with multiple drugs? 5. why is it important to verify the type of seizure by electroencephalogram before starting antiseizure drug therapy? 2. thereby increasing the serum level of unbound valproic acid These drugs induce drug-metabolizing enzymes in the liver and thereby increase the metabolism and hasten the elimination of zonisamide. and phenobarbital decrease effects. lamotrigine dosage must be substantially reduced when the drug is given in a multidrug regimen that includes valproic acid. g. These drugs are benzodiazepines. Eng’s Dilantin level falls within the high end of normal (10–20 mcg/mL). These drugs induce drug-metabolizing enzymes in the liver and thereby increase the rate of metabolism of themselves and of lamotrigine. verapamil h. For a client with a newly developed seizure disorder. What are the indications for use of the major AEDs? 3. Gabapentin should be given at least 2 hours after a dose of an antacid to decrease interference with absorption. valproic acid. his symptoms indicate phenytoin toxicity. Drugs that alter effects of lamotrigine: (1) Valproic acid increases effects. What are the major adverse effects of commonly used AEDs. Drug that increase the effects of phenobarbital: (1) Valproic acid i. but it is important that treatment be based on clinical data. phenobarbital k. Mr. How are the newer drugs similar to or different from phenytoin? Nursing Notes: Apply Your Knowledge Answer: Although Mr. What are the advantages of carbamazepine and valproic acid compared with the benzodiazepines. and diazepam How Can You Avoid This Medication Error? Answer: Blood levels need to remain within a therapeutic range to prevent seizures. thereby decreasing blood levels of carbamazepine. Drugs that decrease effects of oxcarbazepine (1) Phenobarbital. Valproic acid inhibits the liver enzymes that metabolize lamotrigine. phenytoin. phenytoin. Even missing two doses could affect this level. and phenobarbital decrease effects. As a result. f. May increase plasma levels of phenobarbital as much as 40%. phenytoin. Interactions with clonazepam. surgery patients are permitted to take medications with a sip of water. phenytoin. thereby slowing elimination from the body and increasing blood levels of valproic acid Displace valproic acid from binding sites on plasma proteins. lorazepam. thereby increasing blood levels and slowing metabolism of lamotrigine. even when they are NPO. Eng should be referred to his physician for evaluation of Dilantin toxicity and adjustment of Dilantin dosage. Good judgment requires a nurse to check with the physician when significant medications are withheld. phenytoin. Additional drugs that increase effects of valproate: (1) Cimetidine (2) Salicylates j. and phenobarbital? 7. Which of the benzodiazepines are used as antiseizure agents? 6. Drugs that decrease effects of zonisamide (1) Carbamazepine. probably by inhibiting liver metabolizing enzymes. Drugs that alter the effects of gabapentin: (1) Antacids RATIONALE/EXPLANATION These drugs increase activity of hepatic drug-metabolizing enzymes. Frequently. e. Laboratory values are guides for appropriate dosing.

Philadelphia: Lippincott Williams & Wilkins. (2001). medscape. Gidal. St. B. K. Accessed December. K. Approach to the patient with seizures. D. (Updated monthly).). 2001. R. Buck. (2001). . Why is it important when teaching clients to emphasize that none of the AEDs should be stopped abruptly? 10. 7th ed. 21(11). Louis: Facts and Comparisons. Inc. Bourdet. C. 2865–2876.com/UVA/PedPharm/2001/v07. Available: http://pediatrics. 41(3). Oxcarbazepine use in children and adolescents. 01. B.. R. Kim.).CHAPTER 11 ANTISEIZURE DRUGS 201 8. New Rochelle. In H. (2001).. (Ed. B. NY: The Medical Letter. Textbook of therapeutics: Drug and disease management. Delgado-Escueta. Journal of the American Pharmaceutical Association. 1375–1388.). S. 421–436.01. Levetiracetam: A novel antiepileptic drug. In E. & Alldredge. Hovinga. pp. Pharmacologic management of epilepsy in the elderly. E.buck-01. 4th ed.. Humes (Ed.buck/pp0711. Drug facts and comparisons. V. B. Seizure disorders. M. T. A. Pediatric Pharmacotherapy.. 7(11). pp. How can a home care nurse monitor AED therapy during a home visit? SELECTED REFERENCES Alldredge. Gourley (Eds. Handbook of adverse drug interactions.html. V. What is the treatment of choice for an acute convulsion or status epilepticus? 9. 1107–1137. Pharmacotherapy. L. A. 711–716. Herfindal & D. Philadelphia: Lippincott Williams & Wilkins. (2000). (2000). Kelley’s Textbook of internal medicine. (2001). [On-line].n11/pp0711.

Signs and symptoms of the disease also may occur with other CNS diseases. catechol-O-methyltransferase [COMT] inhibitors) or inhibit the actions of acetylcholine (anticholinergic agents) in the brain. 4. You are a home health nurse visiting Mr. The cause of the nerve cell damage is unknown. Rod’s ability to function normally? ᮣ How does each medication work to restore the balance of neurotransmitters? ᮣ What assessment data will you collect to evaluate whether the antiparkinson medications are effective? ᮣ What assessment data should be collected to detect adverse effects of antiparkinson drugs? PARKINSON’S DISEASE arkinson’s disease (also called parkinsonism) is a chronic. ANTIPARKINSON DRUGS Drugs used in Parkinson’s disease increase levels of dopamine (levodopa. the drugs help adjust the balance of neurotransmitters. It occurs equally in men and women. dopamine agonists. 3. People with Parkinson’s disease have an imbalance in these neurotransmitters. His physician started him on levodopa 500 mg tid and benztropine (Cogentin) 1 mg hs. His symptoms included slow. progressive. Rod. The correct balance of dopamine and acetylcholine is important in regulating posture. Rod was diagnosed with Parkinson’s disease 1 week ago. carbon monoxide. Reflect on: ᮣ How can Parkinson’s disease affect Mr. Apply the nursing process with clients experiencing parkinsonism. bradykinesia. genetics. glutamate.chapter 12 Antiparkinson Drugs Objectives AFTER STUDYING THIS CHAPTER. Differentiate the types of commonly used antiparkinson drugs. and voluntary movement. Imbalances of other neurotransmitters (eg. and head injuries and with the use of typical or traditional antipsychotic drugs (eg. Use of the newer “atypical” antipsychotic drugs may reduce the incidence of drug-induced parkinsonism. age-related degeneration. Thus. muscle tone. joint and muscular rigidity). Early-onset parkinsonism (before 45 years) is thought to have a genetic component. degenerative disorder of the central nervous system (CNS) characterized by abnormalities in movement and posture (tremor. fine tremor at rest. gamma aminobutyric acid [GABA]. stooped posture. shuffling gait. monoamine oxidase [MAO] inhibitors. norepinephrine. THE STUDENT WILL BE ABLE TO: 1. Describe major characteristics of Parkinson’s disease. . usually between 50 and 80 years of age. 202 P The basal ganglia in the brain normally contain substantial amounts of the neurotransmitters dopamine and acetylcholine. resulting in a decrease in inhibitory brain dopamine and a relative increase in excitatory acetylcholine. 5. and exposure to toxins (eg. phenothiazines). and serotonin) also occur. Critical Thinking Scenario Mr. organophosphate pesticides) are possible etiologic factors. brain tumors. Discuss therapeutic and adverse effects of dopaminergic and anticholinergic drugs. Classic parkinsonism probably results from destruction or degenerative changes in dopamineproducing nerve cells. Discuss the use of antiparkinson drugs in special populations. and mask-like facial expression. 2.

Selegiline blocks one of the enzymes (MAO-B) that normally inactivates dopamine. Dopamine cannot be used for replacement therapy because it does not penetrate the blood–brain barrier. or a history of melanoma or undiagnosed skin disorders. Contraindications to Use Levodopa is contraindicated in clients with narrow-angle glaucoma. The drugs must be used cautiously in clients with cardiovascular disorders (eg. gastrointestinal obstruction. kidney. or in combination with other antiparkinson drugs. amantadine. renal. levodopa has a shorter duration of action and drug effects “wear off” between doses. there are fewer dopaminergic neurons and thus less storage capacity for dopamine derived from levodopa. Anticholinergic drugs are used in idiopathic parkinsonism to decrease salivation. pergolide. and ropinirole are dopamine agonists that directly stimulate postsynaptic dopamine receptors. Although levodopa does not alter the underlying disease process. usually with levodopa. Bromocriptine is also used in the treatment of amenorrhea and galactorrhea associated with hyperprolactinemia. spasticity. Levodopa readily penetrates the CNS and is converted to dopamine by the enzyme amino acid decarboxylase (AADC). and tremors. an antihistamine (diphenhydramine) is used for parkinsonism because of its strong anticholinergic effects. and in clients taking MAO inhibitor drugs. pramipexole. hepatic. selegiline. Entacapone and tolcapone block another enzyme (COMT) that normally inactivates dopamine and levodopa. In addition. Selegiline. carbidopa is used only to decrease peripheral breakdown of levodopa. pulmonary. pramipexole. For example. amantadine is also used to prevent and treat influenza A viral infections. hemolytic anemia. a course of therapy of approximately 3 months is recommended because symptoms usually subside by then even if the antipsychotic drug is continued. Amantadine increases dopamine release and decreases dopamine reuptake by presynaptic nerve fibers. It relieves all major symptoms. pramipexole. In addition to the primary anticholinergic drugs. or endocrine disorders. It is metabolized to a lesser extent by the enzyme COMT. Anticholinergic drugs are contraindicated in clients with glaucoma. Levodopa (Larodopa. and tolcapone increase dopamine concentrations in the brain and exert dopaminergic activity. carbidopa. ropinirole. INDIVIDUAL ANTIPARKINSON DRUGS Dopaminergic antiparkinson drugs are described in this section. levodopa must be used with caution in clients with severe cardiovascular. Dopar) is the most effective drug available for the treatment of Parkinson’s disease. They are used primarily for people who have minimal symptoms or who cannot tolerate levodopa. Consequently. Anticholinergic drugs decrease the effects of acetylcholine. pergolide. ropinirole. Atropine and scopolamine are centrally active but are not used because of a high incidence of adverse reactions.CHAPTER 12 ANTIPARKINSON DRUGS 203 Dopaminergic Drugs Levodopa. urinary bladder neck obstruction. directly or indirectly. Only anticholinergic drugs that are centrally active (ie. whose concentration is greater in peripheral tissues than in the brain. routes. transient ischemic attacks. liver. hypertension) and liver or kidney disease. prostatic hypertrophy. Some of the other drugs have additional uses. and dosage ranges are listed in Drugs at a Glance: Antiparkinson Drugs. In advanced stages of Parkinson’s disease. The dopamine is stored in presynaptic dopaminergic neurons and functions like endogenous dopamine. In peripheral tissues (eg. names. levodopa. bromocriptine. Levodopa acts to replace dopamine in the basal ganglia of the brain. it may improve a client’s quality of life. selegiline. and myasthenia gravis. entacapone. tachycardia. Anticholinergic Drugs Anticholinergic drugs are discussed in Chapter 21 and are described here only in relation to their use in the treatment of Parkinson’s disease. Anticholinergic agents also are used to relieve symptoms of parkinsonism that can occur with the use . and tolcapone are contraindicated in people with hypersensitivity reactions to the drugs. Tolcapone is contraindicated in people with impaired liver function. As a result. those that penetrate the blood–brain barrier) are useful in treating parkinsonism. Bromocriptine and pergolide are ergot derivatives and therefore are contraindicated in people hypersensitive to ergot alkaloids or those with uncontrolled hypertension. gastrointestinal tract). entacapone. pergolide. especially bradykinesia and rigidity. severe angina pectoris. levodopa is extensively metabolized by decarboxylase. The other drugs are used as adjunctive agents. Levodopa is the mainstay of drug therapy for idiopathic parkinsonism. dysrhythmias. of antipsychotic drugs. Levodopa is a precursor substance that is converted to dopamine. and tolcapone are indicated for the treatment of idiopathic or acquired parkinsonism. Carbidopa is used only in conjunction with levodopa. Mechanisms of Action Dopaminergic drugs increase the amount of dopamine in the brain by various mechanisms. Peripheral metabolism of levodopa can be reduced (and the amounts Indications for Use Entacapone. most levodopa is metabolized in peripheral tissues and large amounts are required to obtain therapeutic levels of dopamine in the brain. If used for this purpose. Bromocriptine. This decreases the apparent excess of acetylcholine in relation to the amount of dopamine.

600 mg daily Diphenhydramine (Benadryl) Procyclidine (Kemadrin) Trihexyphenidyl (Trihexy) PO 0. gradually increased to 5–15 mg daily if necessary reaching the brain can be increased) by giving the AADC inhibitor. reaches peak serum levels within 30 to 90 minutes. 8 g/d. below). Levodopa is metabolized to 30 or more metabolites. 300 mg PO 5 mg twice daily initially. The combination of levodopa and carbidopa greatly increases the amount of available levodopa. PO 2 mg 1–3 times daily. wk 4.125 mg once daily. wk 7.5 mg/d every 2–4 wk if necessary for therapeutic benefit.1 mg/d at bedtime. until therapeutic or adverse effects occur Adults: Drug-induced extrapyramidal reactions. maximal daily dose. 1. wk 2. 1 mg 3 times daily. 0. gradually increased to 5 mg 3–4 times daily if necessary PO 1–2 mg daily initially. up to a maximum of 1. PO 2 mg 3–4 times daily Drug-induced extrapyramidal reactions.15 mg every 3 d to a maximum dose of 6 mg/d if necessary PO wk 1.75 g/d. increase gradually by no more than 0. The rate of dosage increase depends mainly on the client’s tolerance of adverse effects. Sinemet CR PO 1 tab twice daily at least 6 h apart initially.25 mg 3 times daily. chronic manganese poisoning). . IM 2 mg repeated q30min if necessary to a maximum of 8 mg in 24 h PO 25 mg 3 times daily. especially nausea and vomiting. the metabolites are excreted primarily in the urine. gradually increased to 4–6 mg daily if necessary Parkinsonism.5 mg 3 times daily. The two drugs are usually given together in a fixed-dose formulation called Sinemet. IV 10–50 mg.5–1 g/d initially in 3 or 4 divided doses. levodopa is often reserved for clients with significant symptoms and functional disabilities. up to 8 times (1600 mg) daily PO 0. wk 2. IM. depending on dosage of levodopa. gradually increased to 12–15 mg daily. below). up to a maximum of 1. so that the levodopa dosage can be reduced by approximately 70%.05–0.5 mg 2 times daily. maximum dose.125 mg 3 times daily initially. PO 70–100 mg/d. IM 5 mg/kg per day. 1 mg 3 times daily PO 5 mg twice daily. increased by 2. Average maintenance dose.5–1 mg at bedtime initially. Because of side effects and recurrence of parkinsonian symptoms after a few years of levodopa therapy. some of which are pharmacologically active and probably contribute to drug toxicity. 0.75 mg 3 times daily. 1. 0. wk 3. wk 4. 400 mg Children: Drug-induced extrapyramidal reactions. wk 3. Absorption is decreased by delayed gastric emptying.75 mg 3 times daily. 0. up to a maximum of 1.125 mg 2 times daily initially. 0. Levodopa relieves only parkinsonian symptoms in these conditions. 0.25 mg twice a day with meals. juvenile Huntington’s chorea. Crcl 35–59 mL/min. maximum dose. COMT inhibitors. Dosage must be reduced when carbidopa is also given (see carbidopa. PO 1 mg initially. hyperacidity of gastric secretions. 200 mg/d Clients not receiving levodopa: PO 1 tab of 25 mg carbidopa/100 mg levodopa 3 times daily or 1 tab of 10 mg carbidopa/100 mg levodopa 3 or 4 times daily. 0. PO 200 mg with each dose of levodopa/carbidopa. PO 1 tab of 25 mg carbidopa/250 mg levodopa 3 or 4 times daily for clients taking >1500 mg levodopa or 1 tab of 25 mg carbidopa/100 mg levodopa for clients taking <1500 mg levodopa PO 100 mg twice a day PO 1. 0. In addition to treating Parkinson’s disease. maximum dose. 0. increased up to 8 tablets daily and q4h intervals if necessary Clients receiving levodopa: Discontinue levodopa at least 8 h before starting Sinemet. 100 mg.204 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Drugs at a Glance: Antiparkinson Drugs Generic/Trade Name Dopaminergic Agents Levodopa (Larodopa) Routes and Dosage Ranges Carbidopa (Lodosyn) Levodopa/carbidopa (Sinemet) Amantadine (Symmetrel) Bromocriptine (Parlodel) Entacapone (Comtan) Pergolide (Permax) Pramipexole (Mirapex) Ropinirole (Requip) Selegiline (Eldepryl) Tolcapone (Tasmar) Anticholinergic Agents Benztropine (Cogentin) Biperiden (Akineton) PO 0. gradually increased to 50 mg 4 times daily if necessary Adults: Drug-induced extrapyramidal reactions. Levodopa is well absorbed from the small intestine after oral administration.5 mg 3 times daily Renal impairment: Creatinine clearance (Crcl) > 60 mL/min. morning and noon PO 100–200 mg 3 times daily. Crcl 15–34 mL/min. usually within 24 hours. and competition with amino acids (from digestion of protein foods) for sites of absorption in the small intestine.5 mg once daily PO wk 1.5 mg 3 times daily. maximal daily dose. the COMT pathway becomes more important (see entacapone and tolcapone. maximal single dose. Reduce dose gradually if severe adverse effects occur.25 mg 3 times daily.25 mg 3 times daily. wk 6. and has a short serum half-life (1 to 3 hours). 3–6 g/d. increased by 0. When carbidopa inhibits the decarboxylase pathway of levodopa metabolism. every 3–7 d. levodopa also may be useful in other CNS disorders in which symptoms of parkinsonism occur (eg.125 mg 3 times daily.5 mg 3 times daily. wk 5.05–0. increased by 1 tablet every day or every other day until a dosage of 8 tablets daily is reached. carbidopa. 0.

has a half-life of about 2. then every 4 weeks for 6 months. . It is excreted unchanged in the urine. with levodopa/carbidopa. You administer 1 tablet to Mr. Adverse effects are similar for the two drugs. abdominal tenderness. Adverse effects include confusion. Its elimination half-life is 2 to 3 hours and it is metabolized in the liver. Amantadine is well absorbed from the gastrointestinal tract and has a relatively long duration of action. the drugs may also inhibit COMT in the brain and prolong the activity of dopamine at the synapse. dizziness. It is less than 20% bound to plasma proteins and has an elimination half-life of 8 to 12 hours. it is usually given for 2. has carbidopa/ levodopa (Sinemet) 25/100 ordered tid. thereby increasing dopamine levels. These drugs are used only in conjunction with levodopa/ carbidopa. As a result.CHAPTER 12 ANTIPARKINSON DRUGS 205 Carbidopa (Lodosyn) inhibits the enzyme AADC. In advanced stages. Pergolide has a longer duration of action than bromocriptine and may be effective in some clients unresponsive to bromocriptine. Because of several reports of liver damage and deaths from liver failure. Thus. Entacapone is well absorbed with oral administration and reaches a peak plasma level in 1 hour. Carbidopa does not penetrate the blood–brain barrier. Pramipexole is rapidly absorbed with oral administration. less levodopa is decarboxylated in peripheral tissues. Dosage must How Can You Avoid This Medication Error? Mr. Renal failure does not appear to alter drug effects. and dosage of levodopa must be reduced. Tolcapone is also well absorbed with oral administration. but hepatic disease is unlikely to alter drug effects. The drug relieves symptoms rapidly. jaundice. if symptoms of liver failure occur (anorexia. Although carbidopa is available alone. Entacapone (Comtan)and tolcapone (Tasmar) are COMT inhibitors. and much smaller doses of levodopa can be given. dark urine. levodopa). They are approved for both beginning and advanced stages of Parkinson’s disease. Evans. more levodopa reaches the brain. liver aminotransferase enzymes (serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) should be monitored every 2 weeks for 1 year. hallucinations. Most of the drug is excreted unchanged in the urine. It is highly protein bound (98%). renal failure may cause higher-than-usual plasma levels and possible toxicity. only 10% of the drug is metabolized. Ropinirole is also well absorbed with oral administration. Dosage must be reduced with impaired renal function to avoid drug accumulation. When used. As a result. Amantadine increases the release and inhibits the reuptake of dopamine in the brain. Pramipexole (Mirapex) and ropinirole (Requip) are newer drugs that also stimulate dopamine receptors in the brain. liver failure may decrease metabolism. Although there were few instances of liver enzyme elevation or hemoglobin decreases during clinical trials. and increase adverse effects. By inhibiting COMT. It is metabolized by the cytochrome P450 enzymes in the liver to inactive metabolites. Diarrhea was a common adverse effect during clinical trials. then every 2 months. Consequently. to prolong effectiveness and allow reduced dosage of levodopa. Selegiline (Eldepryl) increases dopamine in the brain by inhibiting its metabolism by MAO. It is 40% bound to plasma proteins and has an elimination half-life of 6 hours. allow drug accumulation. Amantadine is often given in conjunction with levodopa. pulmonary and peritoneal fibrosis and constriction of coronary arteries). These drugs are not ergot derivatives and may not cause some adverse effects associated with bromocriptine and pergolide (eg. where it is decarboxylated to dopamine. It reaches peak serum levels in 1–2 hours and steady-state concentrations within 2 days. nausea. a client with Parkinson’s disease. In early stages. These can be reduced by lowering the dose of either levodopa or entacapone. Your pharmacy supplies you with Sinemet 25/250. which are excreted through the kidneys.5 hours. it is most often given in a levodopa/carbidopa fixed-dose combination product called Sinemet. amantadine is considered less effective than levodopa but more effective than anticholinergic agents. tolcapone should be used only in clients who do not respond to other drugs. Although the main mechanism of action seems to be inhibiting the metabolism of levodopa in the bloodstream. Bromocriptine (Parlodel) and pergolide (Permax) are ergot derivatives that directly stimulate dopamine receptors in the brain. and to delay levodopa therapy. one of the drugs can be used alone to improve motor performance. but it loses efficacy with approximately 6 to 8 weeks of continuous administration. clay-colored stools). and is metabolized in the liver to an inactive metabolite. it is recommended that liver enzymes and red blood cell counts be done periodically. or when symptoms worsen. Evans for his morning dose. Less than 10% of ropinirole is excreted unchanged in the urine. 10% is excreted in the urine. The parent drug and the metabolite are 90% excreted through the biliary tract and feces. or if parkinsonian symptoms do not improve after 3 weeks of taking tolcapone. one of the drugs can be used with levodopa and perhaps other antiparkinson drugs to provide more consistent relief of symptoms between doses of levodopa and allow reduced dosage of levodopa.to 3-week periods during initiation of drug therapy with longeracting agents (eg. to improve ability to participate in usual activities of daily living. drowsiness. Compared with other antiparkinson drugs. and vomiting. entacapone and tolcapone increase levels of dopamine in the brain and relieve symptoms more effectively and consistently. They are used in the treatment of idiopathic Parkinson’s disease. be reduced by 50% in the presence of impaired liver function. within 1 to 5 days. COMT plays a role in brain metabolism of dopamine and metabolizes approximately 10% of peripheral levodopa. Peak serum levels are reached in 1 to 3 hours after a dose and steady-state concentrations in about 2 days. MAO exists in two types. Amantadine (Symmetrel) is a synthetic antiviral agent initially used to prevent infection from influenza A virus. Tolcapone should be discontinued if ALT and AST are elevated.

Doses above 10 mg/day should be avoided in Parkinson’s disease. in the brain. • Spend time with the client and encourage socialization with other people. however. which may take several months. At doses higher than 10 mg/day. other exercises. muscle rigidity. If MAO-A is inhibited in the intestine. both of which are found in the CNS and peripheral tissues. At oral doses of 10 mg/day or less. dressing. and neck Mask-like. In early Parkinson’s disease. assisted if necessary. small meals. immobile facial expression Speech problems (eg. These include the following: • Provide physical therapy for heel-to-toe gait training. legs. This life-threatening reaction can also occur with medications that are normally metabolized by MAO. MAO-B metabolizes dopamine. his functional abilities continue to decline. assuming an upright position. Victims of Parkinson’s disease tend to become withdrawn. and self• • • • care abilities Experience improvement of self-concept and body image Increase knowledge of the disease process and drug therapy Take medications as instructed Avoid falls and other injuries from the disease process or drug therapy. and serotonin. His physician prescribes a tricyclic antidepressant. • Help with active and passive range-of-motion exercises. widening stance to increase balance and base of support. eating. Velcro-type fasteners or zippers are easier to handle than buttons. “pill rolling” movements of fingers) Rigidity of arms. isolated. • Encourage ambulation and frequent changes of position. MAO-A acts more specifically on tyramine. mobility. despite treatment with Sinemet. and tremors • Experience improved motor function. Nursing Process Assessment Assess for signs and symptoms of Parkinson’s disease and drug-induced extrapyramidal reactions. Cutting meat. chopped or soft foods may be necessary. low volume. Interventions Use measures to assist the client and family in coping with symptoms and maintaining function. norepinephrine. it is given to enhance the effects of levodopa. selegiline may be effective as monotherapy. epinephrine. selegiline inhibits MAO-B selectively and is unlikely to cause severe hypertension and stroke. giving frequent. • Encourage self-care as much as possible. monotonous tone. As a result. hypotension related to adverse drug effects Planning/Goals The client will: • Experience relief of excessive salivation. It is the main subtype in gastrointestinal mucosa and the liver and is responsible for metabolizing dietary tyramine. depending on the severity and stage of progression: • Slow movements (bradykinesia) and difficulty in chang• • • • • • ing positions. Selegiline inhibition of MAO-B is irreversible and drug effects persist until more MAO is synthesized in the brain. and allowing privacy during mealtime may be helpful. selectivity is lost and metabolism of both MAO-A and MAO-B is inhibited. difficult to understand) . Simmons has had Parkinson’s disease for 4 years and.206 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Nursing Notes: Apply Your Knowledge Mr. tyramine in various foods is absorbed systemically rather than deactivated. and depressed. In advanced disease. These may include the following. Nursing Diagnoses • Bathing/Grooming Self Care Deficit related to tremors • • • • • and impaired motor function Impaired Physical Mobility related to alterations in balance and coordination Disturbed Body Image related to disease and disability Deficient Knowledge: Safe usage and effects of antiparkinson drugs Imbalanced Nutrition: Less Than Body Requirements related to difficulty in chewing and swallowing food Risk for Injury: Dizziness. opening cartons. there is excessive stimulation of the sympathetic nervous system and severe hypertension and stroke can occur. Are these symptoms related to his medications? • • • • • Excessive salivation and drooling Dysphagia Excessive sweating Constipation from decreased intestinal motility Mental depression from self-consciousness and embarrassment over physical appearance and activity limitations. rapid. They are differentiated by their relative specificities for individual catecholamines. Slip-on shoes are easier to manage than laced ones. and other self-care activities Stooped posture Accelerating gait with short steps Tremor at rest (eg. MAO-A and MAO-B. Its addition aids symptom control and allows the dosage of levodopa/carbidopa to be reduced. most MAO activity is due to type B. He comes to the clinic 3 weeks later complaining of constipation and difficulty voiding. The intellect is usually intact until the late stages of the disease process. spasticity. If the client has difficulty chewing or swallowing.

• Interview and observe regarding correct usage of medications. In addition. ✔ Report adverse effects.or Caregiver Administration ✔ Take antiparkinson drugs with or just after food intake to prevent or reduce anorexia. However. The combination provides more effective relief of symptoms and allows lower dosage of levodopa. some adverse effects usually must be tolerated for control of disease symptoms. This schedule decreases stimulating effects that may interfere with sleep if the drug is taken in the evening. For early idiopathic parkinsonism. several drug therapy strategies and combinations are used to delay the start of levodopa therapy and. 1. Drug Selection Choices of antiparkinson drugs depend largely on the type of parkinsonism (idiopathic or drug induced) and the severity of symptoms. Adverse effects can often be reduced by changing drugs or dosages. ✔ Do not crush or chew Sinemet CR. However. rigidity. . loss of effectiveness in a few years. especially when assuming an upright position. For drug-induced parkinsonism or extrapyramidal symptoms. and slow disease progression. nausea. This is usually a therapeutic effect in Parkinson’s disease. once started. Although all four of the available dopamine agonists are similarly effective. possible acceleration of the loss of dopaminergic neurons in the brain). minimize adverse drug effects.CHAPTER 12 ANTIPARKINSON DRUGS 207 • Schedule rest periods. and vomiting. excessive mouth dryness causes discomfort and dental caries. to reduce levodopa dosage. an anticholinergic agent is the drug of choice. if needed. several drugs may be used as monotherapy. Evaluation • Interview and observe for relief of symptoms. Prescription and nonprescription drugs may interact with antiparkinson drugs to increase or decrease effects. Both anticholinergics and levodopa may cause mouth dryness. when symptoms and functional disability are relatively mild. ✔ Decrease excessive mouth dryness by maintaining an adequate fluid intake (2000–3000 mL daily if not contraindicated) and using sugarless chewing gum and hard candies. This is necessary to avoid adverse drug interactions. CLIENT TEACHING GUIDELINES Antiparkinson Drugs General Considerations ✔ Beneficial effects of antiparkinson drugs may not occur for a few weeks or months. • Provide facial tissues if drooling is a problem. do not stop taking them before they have had a chance to work. because of difficulties with levodopa therapy (eg. impaired physical dexterity. maintain functional ability in activities of daily living. An anticholinergic agent may be the initial drug of choice in clients younger than 60 years of age. A dopamine agonist is usually given with levodopa/ carbidopa. adverse effects. b. especially when tremor is the major symptom. ✔ Change positions slowly. and wear elastic stockings. b. 2. It is formulated to be released slowly. ✔ Take or give selegiline in the morning and at noon. PRINCIPLES OF THERAPY Goals of Treatment The goals of antiparkinson drug therapy are to control symptoms. An anticholinergic relieves tremor in approximately 50% of clients. to prevent dizziness from a drop in blood pressure. a. • Interview and observe for increased mobility and participation in activities of daily living. ✔ Do not take other drugs without the physician’s knowledge and consent. shuffling gait. a combination of medications is used. impaired speech. crushing or chewing destroys this feature. Amantadine may be useful in relieving bradykinesia or tremor. c. and tremor. a. c. An anticholinergic agent may be given with levodopa alone or with a levodopa/carbidopa combination. A dopamine agonist may improve functional disability related to bradykinesia. Self. ✔ Avoid driving an automobile or operating other potentially hazardous machinery if vision is blurred or drowsiness occurs with levodopa. Two advantages of combination therapy are better control of symptoms and reduced dosage of individual drugs. For advanced idiopathic parkinsonism. 3. Amantadine may be given in combination with levodopa or other antiparkinson agents. the newer agents (pramipexole and ropinirole) may cause fewer or less severe adverse effects than bromocriptine and pergolide. Tremor and rigidity are aggravated by fatigue and emotional stress.

with ropinirole. f. Selegiline may be given with levodopa/carbidopa. Doses need to be adjusted as parkinsonism progresses. agitation. A levodopa /carbidopa combination is available in three dosage formulations (10 mg carbidopa /100 mg levodopa. With pramipexole. Fever may occur in any age group. The optimal dose is the lowest one that allows the client to function adequately. or maximum drug dosage is achieved. When the drugs are discontinued. in contrast to AADC inhibitors. Dosage must be individualized for levodopa and carbidopa. 50 mg carbidopa/ 200 mg levodopa) of sustained-release tablets (Sinemet CR). Sinemet CR is not as well absorbed as the short-acting form. but heatstroke is more likely to occur in older adults. Optimal dosage may not be established for 6 to 8 weeks with levodopa. the enzyme that carbidopa inhibits. Although evidence is limited and opinions differ. Dosage of levodopa/ carbidopa may need to be reduced because of an age-related decrease in peripheral AADC. antiparkinson drugs are most likely to be used for other purposes in children. and a client Use in Older Adults Dosage of amantadine may need to be reduced because the drug is excreted mainly through the kidneys and renal function is usually decreased in older adults. dry mouth. because levodopa becomes less effective after approximately 5 to 7 years. and high environmental temperatures. However. dosage is started at low levels and gradually increased over several weeks. 2. hallucinations. therapeutic effects may be increased and adverse effects decreased by frequent administration of small doses. With pramipexole and ropinirole. Selegiline and entacapone may both be used with levodopa/carbidopa because entacapone acts peripherally and selegiline acts in the brain. Only 5% to 10% of a dose of levodopa reaches the CNS. many other drugs have significant anticholinergic activity. However. A daily dose of approximately 70 to 100 mg of carbidopa is required to saturate peripheral amino acid decarboxylase. 6. and bromocriptine (<15 years). When combinations of drugs are used. dosage adjustments of individual components are often necessary. The general rule is to start with a low initial dose and gradually increase the dosage until therapeutic effects. 5. However. being transferred to Sinemet CR needs a dosage increase of approximately one third. With levodopa. even with the addition of carbidopa. and urinary retention. Various preparations can be mixed to administer optimal amounts of each ingredient. The levodopa/carbidopa combination is probably the most effective drug when bradykinesia and rigidity become prominent. In addition to the primary anticholinergics. 4. simultaneous administration of COMT and AADC inhibitors significantly increases the plasma half-life of levodopa. when a dopaminergic drug is added to a regimen containing levodopa/carbidopa. mental confusion. Additional guidelines include the following. lower doses are indicated in older adults and those with renal impairment. Use in Children Safety and effectiveness for use in children have not been established for most antiparkinson drugs. However. and psychosis may occur. They also decrease sweating and may cause fever or heatstroke. When centrally active anticholinergics are given for Parkinson’s disease. When changes are made in a drug therapy regimen. for example. When levodopa is added to a regimen of anticholinergic drug therapy. dosage should be gradually increased to the desired therapeutic level. Drug Dosage The dosage of antiparkinson drugs is highly individualized. 4. many clinicians use other drugs first and reserve levodopa for use when symptoms become more severe. When carbidopa is given with levodopa. one change at a time is recommended so that effects of the change are clear. anticholinergics are sometimes given to children who have drug-induced extrapyramidal reactions. levodopa (<12 years). dosage of levodopa/carbidopa must be reduced. selegiline may have a neuroprotective effect and slow the loss of dopaminergic neurons in the brain. 3. adverse effects. 25 mg carbidopa/100 mg levodopa. which increase the bioavailability of levodopa without increasing its plasma half-life. including the centrally acting anticholinergics (all ages). the anticholinergic drug need not be discontinued or reduced in dosage. the dosage of levodopa must be reduced by approximately 75%. 1. Entacapone is used only with levodopa/carbidopa. strenuous activity. especially with cardiovascular disease. e. Anticholinergic drugs may cause blurred vision. Inhibition of levodopa/dopamine metabolism is a valuable addition to levodopa as an exogenous source of dopamine. because of its association with liver failure. Amantadine for influenza A prevention or treatment is not recommended for neonates or infants younger than 1 year of age but may be given to children 9 to 12 years of age.208 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM d. they should be tapered in dosage over 1 week. and 25 mg carbidopa /250 mg levodopa) of immediaterelease tablets (Sinemet) and two dosage formulations (25 mg carbidopa/100 mg levodopa. tachycardia. These include some . Because parkinsonism is a degenerative disorder of adults. In addition. lower doses may be needed with hepatic impairment. Tolcapone should be used only when other drugs are ineffective.

In addition. Do not crush Sinemet CR and instruct clients not to chew the tablet. Give selegiline in the morning and at noon. and clients should be closely monitored for adverse drug effects. but they are adverse effects when the drugs are used in other disorders. observe for decreased tremor. dosage should be minimized. tricyclic antidepressants. dressing) take longer and require considerable effort by clients with parkinsonism. c. and sweating. To prevent or reduce nausea and vomiting Crushing and chewing destroys the controlled-release feature of the formulation. as levodopa dosage approaches 2–3 g/d. Therapeutic effects are usually evident within 2–3 weeks. but may not reach optimum levels for 6 months. Do not give levodopa with iron preparations or multivitaminmineral preparations containing iron. With anticholinergic agents. Administer accurately a. dosage reductions are not needed. observe for improvement in mobility. posture. Use in Renal Impairment Home Care Amantadine is excreted primarily by the kidneys and should be used with caution in clients with renal failure. teaching may be needed about preventing or managing adverse drug effects. however. combinations of drugs with anticholinergic effects should be avoided. The home care nurse can help clients and caregivers understand that the purpose of drug therapy is to control symptoms and that noticeable improvement may not occur for several weeks. In addition. Observe for therapeutic effects a. speech therapists. drooling. balance. vated liver enzymes and a few deaths from liver failure have been reported. 2. Drooling and seborrhea may be abolished. tolcapone metabolism is impaired and plasma drug levels are high. To decrease central nervous system (CNS) stimulating effects that may interfere with sleep if the drug is taken in the evening (continued ) . liver transaminase enzymes should be monitored frequently. Older clients are at increased risk of having hallucinations with dopamine agonist drugs. Caregivers may need to be informed that most activities (eg. periodic measurements of liver transaminase enzymes are recommended. b. Although liver failure has not been associated with entacapone. Give most antiparkinson drugs with or just after food. no dosage adjustments are needed for renal impairment. d.CHAPTER 12 ANTIPARKINSON DRUGS 209 antihistamines. entacapone can be given without regard to meals. With levodopa and dopaminergic agents. In addition. Dosage should be reduced and maintenance dosage should be less than the 600 mg daily recommended for noncirrhotic clients. With tolcapone. When an anticholinergic is needed by an older adult. salivation. ele- NURSING ACTIONS NURSING ACTIONS Antiparkinson Drugs RATIONALE/EXPLANATION 1. including those in over-the-counter cold remedies and sleep aids. speech. the nurse can encourage clients to consult physical therapists. pramipexole dosage may need to be reduced in older adults with impaired renal function. Iron decreases absorption of levodopa. Use in Hepatic Impairment Ropinirole should be used cautiously in hepatic impairment and dosage may need to be reduced. With ropinirole and entacapone. and mood may be elevated. and self-care ability. Decreased salivation and sweating are therapeutic effects when these drugs are used in Parkinson’s disease. With pramipexole. eating. and phenothiazine antipsychotic drugs. clearance is reduced in clients with moderate or severe renal impairment and lower initial and maintenance doses are recommended. handwriting. In clients with hepatic cirrhosis. and dietitians to help maintain their ability to perform activities of daily living. Also. In clients with noncirrhotic liver disease. b. gait.

confusion. gradually increasing dosage. administering smaller doses more frequently or adding carbidopa so that dosage of levodopa can be reduced. Observe for adverse effects a. Dyskinesia eventually develops in most people who take levodopa. and vomiting (2) Orthostatic hypotension—check blood pressure in both sitting and standing positions q4h while the client is awake. This effect is most likely to occur with large doses of trihexyphenidyl (Artane) or benztropine (Cogentin). observe for: (1) Anorexia. Compared with other antiparkinson drugs. observe for: (1) CNS stimulation—insomnia. These are most likely to occur with benztropine. With levodopa. and sedation is attributed to the antihistamine effect. blurred vision. bluish discoloration of skin on the legs (continued ) . With amantadine. This effect is common during the first few weeks but usually subsides eventually.210 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM NURSING ACTIONS 3. People with pre-existing coronary artery disease may need a beta-adrenergic blocking agent (eg. They may be minimized by giving levodopa with food. amantadine produces few adverse effects. nausea. The ones that occur are mild. hallucinations (2) Livedo reticularis—patchy. observe for atropine-like effects. However. (4) Constipation. Carbidopa may heighten this adverse effect. mouth. ataxia. Many people prefer dyskinesia to lowering drug dosage and subsequent return of the parkinsonism symptoms. adverse effects increase if daily dosage exceeds 200 mg. hallucinations. mental confusion. additive effects may occur. It can be minimized by arising slowly from supine or sitting positions and by wearing elastic stockings. This fluctuation may indicate progression of the disease process. It usually occurs with long-term use of amantadine and disappears when the drug is discontinued. (3) Cardiac arrhythmias (tachycardia. It is related to duration of levodopa therapy rather than dosage. restlessness. They may be severe because decreased intestinal motility and constipation also are characteristics of Parkinson’s disease. slurred speech. such as: (1) Tachycardia and palpitations (2) Excessive CNS stimulation (tremor. delirium (6) Abrupt swings in motor function (on–off phenomenon) c. hyperexcitability. and there is no way to prevent it except by decreasing levodopa dosage. It may occur with levodopa. and face or the whole body (5) CNS stimulation—restlessness. Ocular effects are due to paralysis of accommodation and relaxation of the ciliary muscle and the sphincter muscle of the iris. This is a benign but cosmetically unappealing condition. With anticholinergic drugs. These effects result from decreased gastrointestinal motility and muscle tone. premature ventricular contractions) and increased myocardial contractility (4) Dyskinesia—involuntary movements that may involve only the tongue. thus. paralytic ileus (5) Urinary retention (6) Dilated pupils (mydriasis). The drug has antihistaminic and anticholinergic properties. These symptoms usually disappear after a few months of drug therapy. transient. agitation. dizziness. and reversible. propranolol) to counteract these effects. This reaction is caused by loss of muscle tone in the bladder and is most likely to occur in elderly men who have enlarged prostate glands. photophobia b. Levodopa and its metabolites stimulate beta-adrenergic receptors in the heart. impaction. delirium) (3) Sedation and drowsiness RATIONALE/EXPLANATION These effects may occur with usual therapeutic doses but are not likely to be serious except in people with underlying heart disease. confusion. It often occurs after long-term levodopa use. This is more likely to occur with levodopa/carbidopa combination drug therapy.

hallucinations. abdominal pain g.CHAPTER 12 ANTIPARKINSON DRUGS 211 NURSING ACTIONS d. Drugs that increase effects of anticholinergic drugs: (1) Antihistamines. vomiting. which is a side effect of anticholinergic drug therapy. observe for: (1) Nausea (2) Confusion. insomnia (2) Nausea. drowsiness (4) Dyskinesias (5) Orthostatic hypotension f. carbidopa. drowsiness (3) Dyskinesias and dystonias (4) Hallucinations (5) Orthostatic hypotension 4. These effects are unlikely to occur with selegiline. including isocarboxazid (Marplan). (continued ) . selectivity may be lost at doses higher than the recommended 10 mg/d. dizziness. constipation (2) Dizziness. diarrhea. epinephrine. dyskinesias. which more selectively inhibits the metabolism of dopamine. they usually disappear with a decrease in dosage. observe for: (1) CNS effects—agitation. levodopa should not be started within 3 weeks after an MAO-A inhibitor is discontinued. Drugs that decrease effects of anticholinergic drugs: (1) Cholinergic agents c. ataxia. Observe for drug interactions a. confusion. pramipexole. observe for: (1) Anorexia. Effects of MAO-A inhibitors persist for 1–3 weeks after their discontinuation. bradykinesia. Selegiline is used with levodopa. With bromocriptine and pergolide. With pramipexole and ropinirole. anticholinergic agents. an MAO-B inhibitor. If adverse effects do occur. thiothixene (Navane). observe for: (1) Nausea (2) Confusion and hallucinations (3) Hypotension e. These effects occurred more commonly than others during clinical trials. and stroke may occur. and tranylcypromine (Parnate) RATIONALE/EXPLANATION These symptoms are usually mild and can be minimized by starting with low doses and increasing the dose gradually until the desired effect is achieved. However. nausea. With selegiline. pergolide. These effects occurred more commonly than others during clinical trials. ropinirole. These drugs potentiate levodopa effects and increase the risk of cardiac arrhythmias in people with heart disease. Heart palpitations. These drugs counteract the inhibition of gastrointestinal motility and tone. bromocriptine. The combination of a catecholamine precursor (levodopa) and MAO-A inhibitors that decrease metabolism of catecholamines can result in excessive amounts of dopamine. These drugs are often used in combination for treatment of Parkinson’s disease. tolcapone (2) Tricyclic antidepressants (3) Monoamine oxidase type A (MAO-A) inhibitors. hypertensive crisis. Also. Levodopa and MAO-A inhibitors should not be given concurrently. Drugs that increase effects of levodopa: (1) Amantadine. These drugs have anticholinergic properties and produce additive anticholinergic effects. disopyramide (Norpace). headache. hallucinations (3) Dizziness. phenelzine (Nardil). and tricyclic antidepressants b. phenothiazines. selegiline. and norepinephrine. entacapone. With entocapone and tolcapone.

Factor. What are the major adverse effects of antiparkinson drugs. & Dole. and less reaches the CNS.. Medical Clinics of North America. Pyridoxine stimulates decarboxylase. The mechanisms by which most of these drugs decrease effects of levodopa are not clear.. 2915–2918. 415–443. Kuzel. S. M.. where antiparkinson effects occur. (2000). (1999). This interaction does not occur when carbidopa is given with levodopa. antipsychotics such as phenothiazines. they also may decrease effects of levodopa by delaying gastric emptying. 7th ed. Philadelphia: Lippincott Williams & Wilkins. Ropinirole: A dopamine agonist for the treatment of Parkinson’s disease. K. possibly by as much as 50%. S. Porth (Ed. Hauser. 83. American Journal of Health-System Pharmacy. benzodiazepines (eg. In C. D. When administering Sinemet 25/250.). Iron binds with levodopa and reduces levodopa absorption. R. When administering a combination product. E. M. (1999). (Updated monthly). Drugs that decrease effects of dopaminergic antiparkinson drugs: (1) Antipsychotic drugs (2) Metoclopramide These drugs are dopamine antagonists and therefore inhibit the effects of dopamine agonists. How do the antiparkinson drugs act to alter the level of the deficient neurotransmitter? Chen. & Curtis. reduce dosage as much as possible? 5. M. (2000). Reich. enhanced anticholinergic effects are seen. Drugs that decrease effects of levodopa: (1) Anticholinergics RATIONALE/EXPLANATION Although anticholinergics are often given with levodopa for increased antiparkinson effects. including urinary retention and constipation. Humes (Ed. Simmons to his physician to see if another antidepressant with fewer anticholinergic side effects could be used. 217–224. antiemetics. C. Pathophysiology: Concepts of altered health states. once started. J. pp. Evans. Dopamine agonists.). (2) Alcohol. R.. In this situation.212 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM NURSING ACTIONS d. Refer Mr. In E. Review and Application Exercises 1.. & Shimomura. A. & Zesiewicz. What are the advantages and disadvantages of the various drugs used to treat parkinsonism? 4. haloperidol (Haldol).. pp. S. Journal of Neuroscience Nursing. 3. Herndon. Textbook of therapeutics: Drug and disease management. How Can You Avoid This Medication Error? Answer: This medication error occurred because the wrong dose of levodopa was given to Mr. more levodopa is metabolized in peripheral tissues. diazepam [Valium]). (2000). the Sinemet provided contained 25 mg of carbidopa and 250 mg of levodopa. . Both Sinemet and tricyclic antidepressants have anticholinergic side effects. and thiothixene (Navane) (3) Oral iron preparations (4) Pyridoxine (vitamin B6) e. Phenothiazines block dopamine receptors in the basal ganglia. T. A. 32(4). K. Young. pp. J. Drug facts and comparisons. 6th ed. A. What is the rationale for various combinations of antiparkinson drugs? 6. Tachycardia and palpitations can also occur. D. and how can they be minimized? SELECTED REFERENCES Nursing Notes: Apply Your Knowledge Answer: Yes. Herndon. R. J. 83. 1139–1155. Parkinson’s disease and related disorders. Medical Clinics of North America. (1999). When these medications are given together. Gourley (Eds. you give the patient 250 mg of levodopa rather than the 100 mg that was ordered. D. St. 1123–1157. 216–221. Why is it desirable to delay the start of levodopa therapy and. Porth. As a result. Parkinson’s disease revisited. G. Parkinsonism.). it is important that the dosage be correct for each medication. Call the pharmacy and request that Sinemet 25/100 be provided. Alterations in motor function. A. 393–414. Louis: Facts and Comparisons. Management of early Parkinson’s disease. Philadelphia: Lippincott Williams & Wilkins. In H. T. Which neurotransmitter is deficient in idiopathic and drug-induced parkinsonism? 2. M. 4th ed. This causes more levodopa to be metabolized in the stomach and decreases the amount available for absorption from the intestine. Herfindal & D. (2002). 56. Kelley’s Textbook of internal medicine. the enzyme that converts levodopa to dopamine. Philadelphia: Lippincott Williams & Wilkins. C.

Stimuli that precipitate spasms vary from one individual to another and may include muscle stretching. Spasms may involve alternating contraction and relaxation (clonic) or sustained contraction (tonic). dressing.chapter 13 Skeletal Muscle Relaxants Objectives AFTER STUDYING THIS CHAPTER. Describe nonpharmacologic interventions to relieve muscle spasm and spasticity. and has a pattern of exacerbations and remissions. mobility. spasticity requires treatment when it impairs safety. Myelin normally insulates the neuron from electrical activity and conducts electrical impulses rapidly along nerve fibers. Muscle spasm may occur with musculoskeletal trauma or inflammation (eg. Differentiate uses and effects of selected drugs. spinal cord. arthritis). and 213 . bladder infections or stones. It involves destruction of portions of the myelin sheath that covers nerves in the brain. he continues to have pain and muscle spasms. Discuss common symptoms/disorders for which skeletal muscle relaxants are used. It is also encountered with acute or chronic low back pain. subacute. sustaining trauma to his back and shoulder. self-care in hygiene. Although no bones were broken. strains. occurs more often in women than in men. and the ability to perform activities of daily living (eg. His physician orders Tylox PRN for the pain and cyclobenzaprine (Flexeril) tid for muscle spasms. (Neuromuscular blocking agents used as adjuncts to general anesthesia for surgery are discussed in Chap. Each person needs to be assessed for personal precipitating factors. Critical Thinking Scenario John Moore was in an automobile accident 5 days ago. eating. and optic nerve. fibrotic lesions are formed and nerve conduction is slowed or blocked around the lesions. Multiple sclerosis (MS) is a major cause of neurologic disability among young and middle-aged adults.) S Muscle Spasm Muscle spasm or cramp is a sudden. dantrolene). sprains. baclofen. 2. constipation and bowel distention. It occurs with neurologic disorders such as spinal cord injury and multiple sclerosis. which probably results from inflammation). or infections. a common condition that is primarily a disorder of posture. painful muscle contraction that occurs with trauma or an irritant. Apply the nursing process with clients experiencing muscle spasm or spasticity. Spasticity Spasticity involves increased muscle tone or contraction and stiff. When myelin is destroyed (a process called demyelination. so they can be avoided when possible. and work or recreational activities). 3. although its cause is unknown. Lesions in various states of development (eg. Reflect on: ᮣ Why are two different medications ordered to manage John’s discomfort? ᮣ What nonpharmacologic treatments can be used to promote comfort? ᮣ What teaching needs to be done before sending John home? SKELETAL MUSCLE RELAXANTS keletal muscle relaxants are used to decrease muscle spasm or spasticity that occurs in certain neurologic and musculoskeletal disorders. It is considered an autoimmune disorder that occurs in genetically susceptible individuals. THE STUDENT WILL BE ABLE TO: 1. In patients with spinal cord injury. acute. involuntary. 14. awkward movements. Treatment measures include passive range-of-motion and muscle-stretching exercises and antispasmodic medications (eg. 4. bursitis.

environmental temperature extremes. Other researchers are trying to develop methods for enhancing nerve conduction velocity in demyelinated nerves. Common . Occasionally. or a placebo effect. researchers have discovered that nerve cells can be repaired (remyelinated) if the process that damaged the myelin is stopped before the oligodendrocytes (the cells that form myelin) are destroyed. it is uncertain whether oral administration of usual doses exerts a beneficial effect in acute or chronic disorders. baclofen may be given intrathecally through an implanted subcutaneous pump. sit in a wheelchair. It inhibits the release of calcium in skeletal muscle cells and thereby decreases the strength of muscle contraction. Avoiding environmental heat and conditions that cause fever may also help because an elevated body temperature slows nerve conduction and often aggravates MS symptoms. and excessive fatigue. muscular relaxation. It is metabolized in the liver and excreted in urine. In cases of severe spasticity. Orphenadrine and cyclobenzaprine have high levels of anticholinergic activity and therefore should be used cautiously with glaucoma. 24). diazepam. Mechanism of Action All skeletal muscle relaxants except dantrolene are centrally active drugs. self. dressing). subcutaneous pump. In addition. methotrexate) are used to treat progressive disease. It is unclear whether relief of pain results from sedative effects. Muscle weakness and other symptoms vary according to the location and duration of the myelin damage. routes and dosages ranges are listed in Drugs at a Glance: Skeletal Muscle Relaxants. Betaseron) or glatiramer (Copaxone) is given to prevent relapses. the drug is given orally for 1–3 days to prevent recurrence of symptoms. interferon beta (Avonex. For example. Drug therapy for MS may involve several types of medications for different types and stages of the disease. exposure to cold by wearing a cooling vest or exercising in cool water temporarily increases the rate of nerve conduction and improves symptoms in some people. or dantrolene. Contraindications to Use Most skeletal muscle relaxants cause CNS depression and have the same contraindications as other CNS depressants. Dantrolene also is indicated for prevention and treatment of malignant hyperthermia. Indications for Use Skeletal muscle relaxants are used primarily as adjuncts to other treatment measures such as physical therapy. eating. parenteral agents are given to facilitate orthopedic procedures and examinations. and tizanidine inhibits motor neurons in the brain. Pharmacologic action is usually attributed to general depression of the central nervous system (CNS). The person with minimal symptoms does not require treatment. operating potentially hazardous machinery). Baclofen and diazepam increase the effects of gammaaminobutyric acid. skeletal muscle rigidity. tizanidine. including antidepressants for depression and skeletal muscle relaxants for spasticity. and lasts 4 to 8 hours. Baclofen (Lioresal) is used mainly to treat spasticity in MS and spinal cord injuries. methocarbamol) relieves pain associated with acute musculoskeletal trauma or inflammation. The drugs should not be given if they cause excessive muscle weakness and impair rather than facilitate mobility and function. In some cases. but should be encouraged to maintain a healthy lifestyle. For intraoperative malignant hyperthermia. or participate in self-care activities of daily living (eg. It is contraindicated in people with hypersensitivity reactions to it and those with muscle spasm from rheumatic disorders. The action of oral baclofen starts in 1 hour. peaks in 2 hours. fever. and cyanosis. They should be used cautiously in clients with impaired renal or hepatic function or respiratory depression. cardiac arrhythmias. the drug is given intravenously. It can be given orally and intrathecally through an implanted. its half-life is 3 to 4 hours. and symptoms are treated with a variety of drugs. although parenteral administration of some drugs (eg. Check the pump manufacturer’s literature for information about pump implantation and drug infusion techniques. In spastic disorders. For preoperative prophylaxis in people with previous episodes of malignant hyperthermia. Acute exacerbations are treated with corticosteroids (see Chap. urinary retention. decreasing spasticity may not be desirable because clients with severe leg weakness may require some degree of spasticity to ambulate. Physical therapy may help maintain muscle tone. and in clients who must be alert for activities of daily living (eg. Spasticity may be controlled with the use of baclofen. a rare but life-threatening complication of anesthesia characterized by hypercarbia. the drug is given orally for 1 to 2 days before surgery. Dosage must be reduced in clients with impaired renal function. infections. In recent years. Those with more extensive symptoms should try to avoid emotional stress. immunosuppressive drugs (eg. an inhibitory neurotransmitter. metabolic acidosis. or tachycardia. driving a car.214 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM chronic) often occur at multiple sites in the CNS. and occupational therapy may help maintain ability to perform activities of daily living. Dantrolene is the only skeletal muscle relaxant that acts peripherally on the muscle it- INDIVIDUAL DRUGS Individual skeletal muscle relaxants are described below. skeletal muscle relaxants are indicated when spasticity causes severe pain or inability to tolerate physical therapy. After an occurrence during surgery. but may involve blockage of nerve impulses that cause increased muscle tone and contraction.

IV.5 hours. headache. if used long term or in high doses. IV 60 mg twice daily PO 4 mg q6–8h initially. When discontinued. Intrathecal via implanted pump: Dosage varies widely. not to exceed 0. oral. symptoms of withdrawal if stopped abruptly).CHAPTER 13 SKELETAL MUSCLE RELAXANTS 215 Drugs at a Glance: Skeletal Muscle Relaxants Routes and Dosage Ranges Generic/Trade Name Baclofen (Lioresal) Adults PO 5 mg 3 times daily for 3 days. then 20 mg 3 times daily. and weakness. intramuscular. 10 mg 3 times daily for 3 days. Oral drug acts within 30 minutes. dizziness. above. The drug is contraindicated in clients with intermittent porphyria. and impaired motor coordination. see manufacturer’s recommendations. it can cause physical dependence (ie. 15 mg 3 times daily for 3 days. Chlorphenesin (Maolate) is used to relieve discomfort from acute. reduced to 1. 60 mg daily PO 25 mg daily initially. dizziness. Maximum of 3 doses and 36 mg in 24 h PO 0. PO 1 mg/kg per day initially. The drug is metabolized in the liver and excreted in urine.5–2 g 4 times daily for 48–72 hours. adverse effects include drowsiness. musculoskeletal disorders. PO 100 mg twice daily IM. intravenous. maximal recommended dose.8 mg/kg per day in 3 or 4 divided doses IM. dysrhythmias.12–0. 3 weeks. constipation. nausea. dizziness. increased gradually if needed. gradually increased weekly (by increments of 50–100 mg/d) to a maximal dose of 400 mg daily in 4 divided doses Preoperative prophylaxis of malignant hyperthermia: PO 4–8 mg/kg per day in 3–4 divided doses for 1 or 2 days before surgery Intraoperative malignant hyperthermia: IV push 1 mg/kg initially. Do not give IV more than 3 days. painful. IV 0. PO. Carisoprodol (Soma) is used to relieve discomfort from acute. heart block) or hyperthyroidism. peaks in 1 to 2 hours and lasts 4 to 6 hours. peaks in 4 to 6 hours and lasts 12 to . dosage should be tapered and the drug withdrawn over 1 to 2 weeks. hypotension. recent myocardial infarction. if necessary. fatigue. insomnia. confusion. half-life is 3. nausea.0 g 4 times daily for maintenance IM 500 mg q8h IV 1–3 g daily at a rate not to exceed 300 mg/min (3 mL of 10% injection). It is metabolized in the liver and has a half-life of 8 hours. continued until symptoms are relieved or a maximum total dose of 10 mg/kg has been given Postcrisis follow-up treatment: PO 4–8 mg/kg per day in 4 divided doses for 1–3 days PO 2–10 mg 3 or 4 times daily IM. a rare metabolic disorder characterized by acute abdominal pain and neurologic symptoms. then 400 mg 4 times daily or less for maintenance as needed PO 10 mg 3 times daily. with the last dose at bedtime PO 800 mg 3 times daily until desired effect attained.6 mg/kg within an 8-h period >12 years: Same as adults <12 years: Safety and effectiveness have not been established Safety and effectiveness have not been established except for treatment of tetanus (IV 15 mg/kg every 6 hours as indicated) Not recommended Safety and effectiveness have not been established IM. Maximal recommended duration. musculoskeletal disorders. Common adverse effects include drowsiness. Cyclobenzaprine (Flexeril) has the same indication for use as carisoprodol and chlorphenesin. not to exceed 400 mg daily Same as adult Dantrolene (Dantrium) Diazepam (Valium) Metaxalone (Skelaxin) Methocarbamol (Robaxin) Orphenadrine citrate (Norflex) Tizanidine (Zanaflex) PO 1.2 mg/kg in a single dose. IV 5–10 mg repeated in 3–4 hours if necessary PO 800 mg 3 or 4 times daily Children <12 years: Safety not established Carisoprodol (Soma) Chlorphenesin (Maolate) <12 years: Not recommended Dosage not established Cyclobenzaprine (Flexeril) <15 years: Safety and effectiveness have not been established. gradually increased to a maximal dose of 3 mg/kg 4 times daily. It is not recommended for long-term use and. confusion. Common adverse effects are drowsiness. Oral drug effects peak in 1 to 3 hours and last 8 to 12 hours. painful.04–0. PO 350 mg 3 or 4 times daily. It is contraindicated in clients with cardiovascular disorders (eg. Oral drug acts in 1 hour.

Its half-life is 3 to 4 hours. peaks in 1 to 2 hours. It is used to relieve spasticity in neurologic disorders (eg. metabolic acidosis. dry mouth. prostatic hypertrophy. it is metabolized in the liver and excreted in urine. In addition. or brain trauma. is metabolized in the liver. such as bruises (ecchymoses). Common adverse effects include drowsiness. and lasts 3 to 4 hours. It has a half life of 2 to 3 hours. parenteral drug acts rapidly but peak and duration of action are unknown. Try to determine the location as specifically as possible. and cyanosis. urinary retention. brown. and myasthenia gravis. Because of its strong anticholinergic effects. coronary insufficiency. a rare but life-threatening complication of anesthesia characterized by hypercarbia. fever.216 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM 24 hours. half-life is 1 to 3 days. peaks in 2 hours and lasts 4 to 6 hours. or signs of inflammation (redness. or black. After an occurrence during surgery. the drug is given orally for 1 to 2 days before surgery. painful. The drug may also discolor urine to a green. the drug is given intravenously. and urinary retention. and precipitating factors (eg. Dantrolene (Dantrium) acts directly on skeletal muscle to inhibit muscle contraction. dry mouth. and spasticity and safe usage of skeletal muscle relaxants . Common adverse effects include drowsiness. It may also cause psychotic symptoms. effects with injected drug also include fainting. constipation. dizziness. Hypotension may be significant and occur at usual doses. the drug is given orally for 1 to 3 days to prevent recurrence of symptoms. musculoskeletal disorders. dizziness. musculoskeletal disorders. Common adverse effects include drowsiness. constipation. Common adverse effects with oral drug include drowsiness. IV drug acts rapidly. peaks in about 5 hours and lasts 6 to 8 hours. Common adverse effects include drowsiness. The drug has a half life of 1 to 2 hours. similar to clonidine. dysrhythmias) and renal or hepatic impairment. tachycardia). heat. and is excreted in urine and feces. but clients should be informed about it. For intraoperative malignant hyperthermia. with jaundice and other symptoms that usually occur within 1 month of starting drug therapy. assess for: • Pain. traumatic injury. nausea. and hypotension. hepatotoxicity and hemolytic anemia may also occur. spinal cord injury. • Accompanying signs and symptoms. Your stock supply has 10 mg Valium in 2-cc vial. painful. pain. incoordination. and urticaria. and is excreted in urine. is metabolized in the liver. dressing). multiple sclerosis. the drug is contraindicated in glaucoma. dry mouth. This is a prominent symptom of muscle spasm and is usually aggravated by movement. The most serious adverse effect is potentially fatal hepatitis. peaks in 4 to 6 hours and lasts 8 to 10 hours. Oral drug acts slowly. This is considered a harmless effect. Her physician orders Valium 50 mg to be given IV stat. dizziness. and nausea. duration. • With muscle spasm. bladder neck obstruction. Tizanidine (Zanaflex) is an alpha2 adrenergic agonist. strenuous exercise). Orphenadrine (Norflex) is used to relieve discomfort from acute. Oral drug acts within 60 minutes. It is given orally and its action starts within 30 to 60 minutes. and hypotension. edema. musculoskeletal disorders. painful. and fatigue. Common adverse effects are drowsiness. spinal cord injury) and to prevent or treat malignant hyperthermia. tachycardia. skeletal muscle rigidity. dizziness. heart failure. eating. and is excreted in urine and feces. dizziness. assess for pain and impaired functional ability in self-care (eg. Liver function tests should be monitored periodically in all clients receiving dantrolene. peaks in 2 hours and lasts 4 to 6 hours. Discuss how you will safely administer this medication. Parenteral drug is contraindicated in clients with renal impairment because the solution contains polyethylene glycol. including hallucinations. Nursing Process Assessment Assess for muscle spasm and spasticity. It should be used cautiously in clients with cardiovascular disease (eg. duodenal obstruction. and anticholinergic effects (eg. constipation. dizziness. These adverse effects do not occur with short-term use of IV drug for malignant hyperthermia. Liver function should be monitored during therapy. It should be used cautiously with renal or hepatic impairment and hypotension. nausea. is metabolized in the liver. It is contraindicated in clients with anemias or severe renal or hepatic impairment. Methocarbamol (Robaxin) is used to relieve discomfort from acute. The action of both oral and parenteral drug Nursing Notes: Apply Your Knowledge Sarah Johnson is experiencing severe muscle spasms. edema. it may also be used to treat tetanus. For preoperative prophylaxis in people with previous episodes of malignant hyperthermia. Nursing Diagnoses • Pain related to muscle spasm • Impaired Physical Mobility related to spasm and pain • Bathing/Hygiene Self-Care Deficit related to spasm and pain • Deficient Knowledge: Nondrug measures to relieve muscle spasm. Oral drug acts within 30 minutes and peaks in 2 hours. Duration of use should not exceed 3 weeks. that is used to treat spasticity in clients with multiple sclerosis. severe spasticity interferes with ambulation and other movement as well as exercises to maintain joint and muscle mobility. tenderness to touch) • With spasticity. as well as the intensity. diarrhea. The drug has a halflife of 14 hours. Metaxalone (Skelaxin) is used to relieve discomfort from acute.

an oral or parenteral drug may be given. antihistamines. and nausea. or other drugs that cause drowsiness. headache. ✔ Avoid herbal preparations that cause drowsiness or sleep. Suddenly stopping baclofen may cause hallucinations. The drugs should be used only when clearly indicated. Dosage should be decreased gradually. ✔ Avoid activities that require mental alertness or physical coordination (eg. 4. • Interview and observe regarding correct usage of medications and nondrug therapeutic measures. CLIENT TEACHING GUIDELINES Skeletal Muscle Relaxants General Considerations ✔ Use nondrug measures. Cyclobenzaprine should not be used longer than 3 weeks. For children. and other adverse effects are higher because of impaired drug metabolism and excretion. muscle spasm. For acute muscle spasm and pain. mental confusion. The major risk occurs with concurrent use of alcohol. operating potentially dangerous machinery) if drowsy from medication. carisoprodol (Soma). moist heat. and cyclobenzaprine (Flexeril). especially with baclofen (Lioresal). The drugs cause sedation and other adverse effects and are recommended for short-term use. Baclofen (Lioresal) is approved for treatment of spasticity in people with multiple sclerosis. 2. stooping rather than bending to lift objects. . safety and effectiveness for use in children 12 years of age and younger have not been established. Strenuous exercise performed on an occasional basis (eg. holding heavy objects close to the body. 5. Parenteral agents are preferred for orthopedic procedures because they have greater sedative and painrelieving effects. stopping the other drugs may cause fatigue. when close supervision is available for monitoring drug effects (especially sedation). sedation related to CNS depression Drug Selection Choice of a skeletal muscle relaxant depends mainly on the disorder being treated: 1. and muscle spasticity without impairing the ability to perform self-care activities of daily living. for short periods. Evaluation • Interview and observe for relief of symptoms. Planning/Goals The client will: • Experience relief of pain and spasm • Experience improved motor function • Increase self-care abilities in activities of daily living • Take medications as instructed • Use nondrug measures appropriately • Be safeguarded when sedated from drug therapy Interventions Use adjunctive measures for muscle spasm and spasticity: • Physical therapy (massage. including kava and valerian. the choice of drug should be limited to those with established pediatric dosages. PRINCIPLES OF THERAPY Use in Older Adults Goal of Treatment The goal of treatment is to relieve pain. ✔ Do not stop drugs abruptly. None of the skeletal muscle relaxants has been established as safe for use during pregnancy and lactation. to decrease muscle spasm and spasticity. exercises) • Bed rest for acute muscle spasm • Relaxation techniques • Correct posture and lifting techniques (eg. Use in Children For most of the drugs. such as exercises and applications of heat and cold. driving an automobile. Self-Administration ✔ Take the drugs with milk or food. Risks of falls. including nonprescription drugs. and when mobility and alertness are not required. ✔ Do not take other drugs without the physician’s knowledge. Any CNS depressant or sedating drugs should be used cautiously in older adults.CHAPTER 13 SKELETAL MUSCLE RELAXANTS 217 • Risk for Injury: Dizziness. and its clinical usefulness may be limited by adverse reactions. It is variably effective. weekly or monthly) is more likely to cause acute muscle spasm. sleeping aids. to avoid nausea and stomach irritation. not lifting excessive amounts of weight) • Regular exercise and use of warm-up exercises. 3.

b. liver function should be assessed before starting either drug The home care nurse is likely to be involved with the use of baclofen. Avoid extravasation with IV methocarbamol. Do not mix parenteral diazepam in a syringe with any other drugs. c. have the client lie down during and at least 15 minutes after administration. and dizziness. the drugs should be stopped.) 2. Thrombophlebitis may occur at IV injection sites. Avoid extravasation with IV diazepam. When the drug is given for acute muscle spasm. and periodically during treatment. Caregivers may need instruction about nonpharmacologic interventions to help prevent or relieve spasticity. To decrease gastrointestinal distress Diazepam is physically incompatible with other drugs. or tizanidine in chronic spastic disorders. and sloughing of tissue may occur at sites of extravasation or IM injections. and inject intramuscular (IM) diazepam deeply into a gluteal muscle. (continued ) . and give IM methocarbamol deeply into a gluteal muscle. (Dividing the dose and giving two injections is preferred. g. e. NURSING ACTIONS NURSING ACTIONS Skeletal Muscle Relaxants RATIONALE/EXPLANATION 1. With IV methocarbamol. Observe for therapeutic effects a. Clients may need continued assessment of drug effects. metaxalone with milk or food. and other care. monitoring of functional abilities. dantrolene. With IV methocarbamol. observe for: (1) Increased ability to maintain posture and balance (2) Increased ability for self-care (eg. assistance in arranging blood tests of liver function. observe for: (1) Decreased pain and tenderness (2) Increased mobility (3) Increased ability to participate in activities of daily living b. inject or infuse slowly. Liver function tests should be monitored periodically in all clients receiving dantrolene. Avoid contact with IV solutions as much as possible. Home Care Use in Hepatic Impairment Dantrolene may cause potentially fatal hepatitis. eating and dressing) (3) Increased tolerance for physical therapy and exercises Therapeutic effects usually occur within 30 minutes after IV injection of diazepam or methocarbamol. Metaxalone and tizanidine can cause liver damage. Thus. When the drug is given for spasticity in chronic neurologic disorders. d. To minimize orthostatic hypotension and other adverse drug effects Parenteral methocarbamol is a hypertonic solution that is very irritating to tissues. Diazepam may cause a precipitate if diluted. The drugs should not be given to clients with preexisting liver disease. dosage of baclofen must be reduced. f. Inject intravenous (IV) diazepam directly into a vein or the injection site nearest the vein (during continuous IV infusions) at a rate of approximately 2 mg/min. hypotension. A slow rate of injection minimizes the risks of respiratory depression and apnea. Give baclofen. If liver damage occurs. To prevent or reduce tissue irritation Rapid administration may cause bradycardia. chlorphenesin. with jaundice and other symptoms that usually occur within 1 month of starting drug therapy. Administer accurately a.218 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Use in Renal Impairment The drugs should be used cautiously in clients with renal impairment.

The drug should be discontinued if hypersensitivity reactions occur.. Alterations in motor function. observe for: (1) Drowsiness. areflexia. Humes (Ed. What are the contraindications to the use of these drugs? 4. pp. 4. Louis: Facts and Comparisons. vomiting (2) Headache. antipsychotic drugs. A 50-mg dose is unsafe and should not be given. R. (2002). flaccid paralysis. Any time you have to administer 10 cc IV push you should question whether the dose is appropriate. (Updated monthly). flushing (3) Nausea. Philadelphia: Lippincott Williams & Wilkins. What are the major adverse effects of these drugs. 4th ed. What are the indications for the use of skeletal muscle relaxants? Drug facts and comparisons. lethargy. 3. anorexia. antidepressants. pruritus (5) Psychological or physical dependence with diazepam and other antianxiety agents b. 1123–1157. Drugs that increase effects of skeletal muscle relaxants: (1) Central nervous system (CNS) depressants (alcohol. especially with tizanidine Nursing Notes: Apply Your Knowledge Answer: Check this order with the physician. What are some nonpharmacologic interventions to use instead of or along with the drugs? SELECTED REFERENCES Review and Application Exercises 1. vomiting. weakness. With a peripherally active agent (dantrolene). respiratory depression. How do skeletal muscle relaxants act to relieve spasm and pain? 2.). Philadelphia: Lippincott Williams & Wilkins. monitoring liver enzymes (aspartate aminotransferase and alanine aminotransferase) during therapy.CHAPTER 13 SKELETAL MUSCLE RELAXANTS 219 NURSING ACTIONS 3. M. These effects are most likely to occur with large oral doses. lethargy. Observe for adverse effects a. These effects are the most common. anaphylaxis) are rare. They are usually transient. nausea. hypotension (4) Hypersensitivity—skin rash. constipation or diarrhea. . Less common effects This potentially serious adverse effect is most likely to occur in people older than 35 years of age who have taken the drug 60 days or longer. Kelley’s Textbook of internal medicine. & Curtis. In H. and how can they be minimized? 5. Hepatotoxicity can be prevented or minimized by administering the lowest effective dose. M. abdominal distress. fatigue. Demyelinating diseases. C. sedative-hypnotics) (2) Monoamine oxidase inhibitors (3) Antihypertensive agents Additive CNS depression with increased risks of excessive sedation and respiratory depression or apnea May potentiate effects by inhibiting metabolism of muscle relaxants Increased hypotension. D. Women over age 35 years who take estrogens have the highest risk. With centrally active agents. pp. Most likely to occur with long-term use of large doses Adverse effects are usually transient. 6th ed. Porth. and discontinuing the drug if no beneficial effects occur within 45 days. L. Richert. These effects occur more often with IV administration of drugs. observe for: (1) Drowsiness and dizziness (2) Blurred vision. R. ataxia. Porth. Serious allergic reactions (eg. antianxiety agents. nervousness (3) Hepatotoxicity RATIONALE/EXPLANATION These are the most common adverse effects. antihistamines. St. J. 2912–2915.. Observe for drug interactions a. tachycardia. (2000). Normal IV Valium dosage is 5–10 mg every 3–4 hours. Pathophysiology: Concepts of altered health states. In C.

. Discuss factors considered when choosing an anesthetic agent. 2. and some treatments. Critical Thinking Scenario You are a nurse working in the postanesthesia recovery unit of an outpatient surgery center. GENERAL ANESTHESIA General anesthesia is a state of profound central nervous system (CNS) depression. Its rapid onset of action is attributed to rapid circulation to the brain and accumulation in the neuronal tissue of the cerebral cortex. analgesia. during which there is complete loss of sensation. Anesthetic drugs are given to prevent pain and promote relaxation during surgery. Describe the nurse’s role in relation to anesthetics and adjunctive drugs. Barbiturates are contraindicated in patients with acute intermittent porphyria. Patients may be given general or local anesthetics for minor surgical procedures. This so-called balanced anesthesia also allows lower dosages of potent general anesthetics. and muscle relaxation. They interrupt the conduction of painful nerve impulses from a site of injury to the brain. Because they are slowly released from fatty tissues back into the bloodstream. Describe characteristics of general and regional/local anesthetic agents. 4. and nursing care. ᮣ Identify priorities of nursing care to maintain patient safety during this period. kidneys) and muscles. An anesthetic barbiturate or propofol may be used alone for anesthesia during brief diagnostic tests or surgical procedures.chapter 14 Anesthetics Objectives AFTER STUDYING THIS CHAPTER. The intravenous (IV) agent produces rapid loss of consciousness and provides a pleasant induction and recovery. heart. The two basic types of anesthesia are general and regional. Your responsibilities include monitoring during the immediate recovery period as the effects of the anesthesia wear off. General anesthesia is usually induced with a fast-acting drug (eg. and then to fatty tissues. 5. some diagnostic tests. Compare general and local anesthetics in terms of administration. drowsiness. liver. 3. a rare hereditary disorder characterized by recurrent attacks of physical and mental disturbances. and memory. client safety. THE STUDENT WILL BE ABLE TO: 1. consciousness. 6. It has three components: hypnosis. Anesthesia means loss of sensation with or without loss of consciousness. Patients are usually discharged on the same day. anesthesia. Duration of action can be prolonged and accumulation is more likely to occur with repeated doses or continuous IV infusion. Reflect on: ᮣ What effects would you expect to see as the general anesthesia wears off? ᮣ Compare and contrast how these effects might be the same or different for the patient receiving local anesthesia. Discuss the rationale for using adjunctive drugs before and during surgical procedures. The drugs are short acting because they are quickly redistributed from the brain to highly perfused organs (eg. pain perception. propofol or thiopental) given intravenously and is 220 maintained with a gas mixture of an anesthetic agent and oxygen given by inhalation. Discuss the use of anesthetics and neuromuscular blocking agents in special populations. and cardiopulmonary depression persist into the postoperative period. childbirth. Several different drugs are usually combined to produce desired levels of these components without excessive CNS depression.

anticholinergics (see Chap. have a higher specific gravity than cerebrospinal fluid. bradycardia. lungs). CNS stimulation or depression. Infiltration involves injecting the local anesthetic solution directly into or very close to the area to be anesthetized. especially sodium. Spinal anesthesia involves injecting the anesthetic agent into the cerebrospinal fluid. prolong anesthetic effects. and other stimuli. Drug groups include antianxiety agents and sedative-hypnotics (see Chap. and gravitate toward the lower (caudal) end of the spinal canal when the client is tilted in a headdown position. The rate and amount of absorption depend mainly on the drug dose and blood flow to the site of administration. Field block anesthesia involves injecting the anesthetic solution around the area to be anesthetized. It is induced by application or injection of local anesthetic drugs. Spinal anesthesia is especially useful for surgery involving the lower abdomen and legs. intercostal and paracervical sites) produce peak plasma levels rapidly. solutions. redistributed by the blood to other body tissues. and control bleeding. client amnesia for the peri- . This action stabilizes and reduces excitability of cell membranes. head and neck. hypotension) of local anesthetics. When a vasoconstrictor drug. 4. When excitability falls low enough. decreased myocardial conduction and contractility. Regional anesthesia is usually categorized according to the site of application. or it may be distal to the point of injection.CHAPTER 14 ANESTHETICS 221 Inhalation anesthetics vary in the degree of CNS depression produced and thereby vary in the rate of induction. brain. Epinephrine also controls bleeding in the affected area. the drugs prevent the cells from responding to pain impulses and other sensory stimuli. Specific types of anesthesia attained with local anesthetic drugs include the following: 1. Duration depends on the chemical characteristics of the drug used and the rate at which it leaves nerve tissue. or lotions designed for use at particular sites. preparations are available for use on eyes. large amounts. Anesthetic effects dwindle and end as drug molecules diffuse out of neurons into the bloodstream. is used most often in obstetrics during labor and delivery. especially when injected or applied to mucous membrane. Local anesthetics for topical use are usually ingredients of various ointments. The area anesthetized may be the site of application. is determined by the site of injection. ears. in turn. CNS depression is determined by the concentration of the drug in the CNS. Hypobaric or light solutions are diluted with distilled water. high concentrations. Solutions of local anesthetics used for spinal anesthesia are either hyperbaric or hypobaric. The neuromuscular blocking agents are described in this chapter. degree of muscle relaxation. 21). 2. This. 5. 6). and concentration of the injected solution. Epidural anesthesia. The drugs act to decrease the permeability of nerve cell membranes to ions. along with a small amount of unchanged drug. or injections into highly vascular areas (eg. which involves injecting the anesthetic into the epidural space. As a result. Epinephrine. in turn. and opioid analgesics (see Chap. This route is also used to provide analgesia (often with a combination of a local anesthetic and an opioid) for clients with postoperative or other pain. ADJUNCTS TO ANESTHESIA Several nonanesthetic drugs are used as adjuncts or supplements to anesthetic drugs. Depth of anesthesia can be regulated readily by varying the concentration of the inhaled anesthetic gas. The body area anesthetized is determined by the level to which the drug solution rises in the spinal canal. and skin. For example. Drug concentration. such as anesthesiologists and nurse anesthetists. onset and duration of anesthesia are prolonged because of slow absorption and elimination of the anesthetic agent. 6. and only with appropriate equipment. and analgesic potency. REGIONAL ANESTHESIA Regional anesthesia involves loss of sensation and motor activity in localized areas of the body. liver. the position of the client. has been added. The metabolites are excreted in the urine. itching. Peripheral nerve block involves injecting the anesthetic solution into the area of a larger nerve trunk or a nerve plexus at some access point along the course of a nerve distant from the area to be anesthetized. oral mucosa. 8). hemorrhoids. such as epinephrine. The drugs are then transported to the liver for metabolism. and gravitate toward the head when the client is tilted in a head-down position. anesthetic potency. and the specific gravity. Some local anesthetic is absorbed into the bloodstream and circulated through the body. Most are discussed elsewhere and are described here only in relation to anesthesia. have a lower specific gravity than cerebrospinal fluid. and eliminated by the lungs. The extent and duration of anesthesia produced by injection of local anesthetics depend on several factors. is often added to a local anesthetic to slow systemic absorption. Systemic absorption accounts for most of the potentially serious adverse effects (eg. Goals of preanesthetic medication include decreased anxiety without excessive drowsiness. a vasoconstrictor. transported past the blood–brain barrier to reach the CNS. In general. Such application makes sensory receptors unresponsive to pain. usually in the lumbar spine. The highest concentrations are found in organs with a large blood supply (eg. 3. The anesthetic blocks sensory impulses at the root of peripheral nerves as they enter the spinal cord. Topical or surface anesthesia involves applying local anesthetics to skin or mucous membrane. nerve impulses cannot be initiated or conducted by the anesthetized nerves. nose. perineum. depends on the rate at which the drug is transported from the alveoli to the blood. Hyperbaric or heavy solutions are diluted with dextrose. heart. General inhalation anesthetics should be given only by specially trained people. amount. mainly to inactive metabolites.

The drugs also vary in routes of elimination. Midazolam has a rapid onset and short duration of action. Artificial ventilation is necessary because these drugs paralyze muscles of respiration as well as other skeletal muscles. bradycardia. such as neostigmine (Prostigmin. with most involving both hepatic and renal mechanisms. and increase client safety by allowing easier induction of anesthesia and smaller doses of anesthetic agents. Anticholinergics Anticholinergic drugs are given to prevent vagal effects associated with general anesthesia and surgery (eg. administration of a reversal agent may be unnecessary. Hypnotic doses are usually given for greater sedative effects. hypotension). rocuronium) that allow spontaneous recovery of neuromuscular function when an IV infusion is discontinued. therefore. coughing. intestine. Anticholinesterase drugs. These drugs may be given the night before to aid sleep and 1 or 2 hours before the scheduled procedure. Neuromuscular Blocking Agents PRINCIPLES OF THERAPY Neuromuscular blocking agents cause muscle relaxation. Various regimens. 20). bradycardia. They are ordered by an anesthesiologist and the choice of a particular drug depends on several factors. Antianxiety Agents and Sedative-Hypnotics Antianxiety agents and sedative-hypnotics are given to decrease anxiety. the third component of general anesthesia. Opioid Analgesics Opioid analgesics induce relaxation and pain relief in the preanesthetic period. synthetic nondepolarizing agents are available and are preferred over succinylcholine in most instances. INDIVIDUAL ANESTHETIC AGENTS General anesthetics are listed in Table 14–1. usually of two or three drugs. With these agents. Muscle paralysis is preceded by muscle spasms. only commonly used depolarizing drug. Like acetylcholine. Useful drugs are atropine and glycopyrrolate (Robinul). The drugs do not cause sedation. and local anesthetics in Table 14–3. the active ingredient of curare. In clients with renal or hepatic impairment. see Chap. There is no antidote except reconstituted fresh-frozen plasma that contains pseudocholinesterase. peritoneum. a muscle relaxant. salivation. are antidotes and can be used to reverse muscle paralysis. Succinylcholine is the Preanesthetic Medications Principles for using preanesthetic drugs (antianxiety agents. Morphine and fentanyl may be given in anesthetic doses in certain circumstances. the parent drug or its metabolites may accumulate and cause prolonged paralysis. and less anesthetic agent is required. a naturally occurring plant alkaloid that causes skeletal muscle relaxation or paralysis. It is often used in ambulatory surgical or invasive diagnostic procedures and regional anesthesia. stomach. and reduces the dose of opioid analgesics required during surgery. The prototype drug is tubocurarine. neuromuscular blocking agents in Table 14–2. Nondepolarizing neuromuscular blocking agents prevent acetylcholine from acting at neuromuscular junctions. produces minimal cardiovascular side effects. which may damage muscles. are used. the specific procedure to be performed and its . The drugs vary in onset and duration of action. unless the recipients are unconscious. the nerve cell membrane is not depolarized. and skeletal muscle contraction does not occur. reduced requirement for inhalation anesthetic. promote rest. mivacurium. A benzodiazepine such as diazepam (Valium) or midazolam (Versed) is often used. opioid analgesics) are the same when these drugs are given before surgery as at other times. the drug combines with cholinergic receptors at the motor endplate to produce depolarization and muscle contraction initially. anticholinergics. and reduced perioperative stress. There are two types of neuromuscular blocking agents: depolarizing and nondepolarizing. Some client-related factors include age. or other viscera and procedures in which pressure is exerted on the eyeball. Several newer. and with surgical procedures in which there is manipulation of the pharynx. As a result. Succinylcholine is normally deactivated by plasma pseudocholinesterase. These drugs potentiate the CNS depression produced by other drugs. the muscle fibers are not stimulated. Repolarization and further muscle contraction are then inhibited as long as an adequate concentration of drug remains at the receptor site. causes amnesia. with succinylcholine. If hyperkalemia develops.222 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM operative period. postanesthetic vomiting). and allow the use of smaller amounts of anesthetic agent. neuromuscular blocking agents should be used very cautiously in clients with renal or hepatic impairment. they can see and hear environmental activities and conversations. trachea. Some have short elimination half-lives (eg. reduced adverse effects associated with some inhalation anesthetics (eg. it is usually mild and insignificant but may cause cardiac dysrhythmias or even cardiac arrest in some situations. Injury to muscle cells may cause postoperative muscle pain and release potassium into the circulation. Consequently. Vagal stimulation occurs with some inhalation anesthetics.

it cannot produce surgical anesthesia. after which halothane is given to maintain anesthesia. rapid recovery with little excitement or nausea and vomiting 2. which causes decreased cardiac output. nonflammable volatile liquid Advantages: 1. Nonexplosive gas. 3. weak anesthetic. opioid analgesics. and more potent inhalation anesthetics. and immune system 7. It is used alone for analgesia in dentistry.CHAPTER 14 ANESTHETICS 223 TABLE 14–1 Generic/Trade Name General Anesthetics Characteristics Remarks General Inhalation Anesthetics Desflurane (Suprane) Similar to isoflurane Enflurane (Ethrane) Nonexplosive. one of oldest and safest anesthetics. decreased adverse effects. similar to halothane but may produce better analgesia and muscle relaxation. Causes cardiac dysrhythmias. Rapid acting. Produces rapid induction with little or no excitement. liver. May cause jaundice and hepatitis 8. or both. nitrous oxide is given to increase analgesic effects. Therefore. hypotension. it may not produce adequate analgesia and muscle relaxation at a dosage that is not likely to produce significant adverse effects. rapid induction and recovery. Used for induction and maintenance of general anesthesia Sevoflurane (Ultane) General Intravenous Anesthetics Opioid analgesic–anesthetic related to fentanyl and Alfentanil (Alfenta) sufentanil. sensitizes heart to catecholamines—increases risk of cardiac dysrhythmias. that is. smooth induction. Depresses contractility of the heart and vascular smooth muscle. Isoflurane (Forane) Used for induction and maintenance of general anesthesia Nitrous oxide Used in balanced anesthesia with IV barbiturates. obstetrics. A nonanalgesic hypnotic used for induction and Etomidate (Amidate) maintenance of general anesthesia May be used as a primary anesthetic or an analgesic adjunct in balanced anesthesia May be used with nitrous oxide and oxygen in maintenance of general anesthesia for short operative procedures such as uterine dilation and curettage (continued ) . good analgesic. Similar to isoflurane Used for induction and maintenance of general anesthesia A frequently used agent Halothane (Fluothane) Halothane has largely been replaced by newer agents with increased efficacy. Isoflurane may cause malignant hyperthermia but apparently does not cause hepatotoxicity. It is safer for prolonged surgical procedures (see “Characteristics”). Although quite potent. and brief surgical procedures. Depresses respiration and may produce hypoxemia and respiratory acidosis (hypercarbia) 6. Does not irritate respiratory tract mucosa. a neuromuscular blocking agent is given to increase muscle relaxation. May cause malignant hyperthermia Similar to halothane but less likely to cause cardiovascular depression and ventricular dysrhythmias. neuromuscular blocking agents. and an IV barbiturate is used to produce rapid. causes no appreciable damage to vital organs unless hypoxia is allowed to develop and persist. 4. and bradycardia 2. renal or hepatic toxicity not reported Nonexplosive. Note: Nitrous oxide is an incomplete anesthetic. Depresses functions of the kidneys. therefore does not increase saliva and tracheobronchial secretions 3. ventricular dysrhythmias are uncommon unless ventilation is inadequate. by itself. increases risk of cardiac dysrhythmias 5. Depresses pharyngeal and laryngeal reflexes. It may be used in balanced anesthesia with other agents. Sensitizes heart to catecholamines. administered with oxygen to prevent hypoxia. nonflammable volatile liquid. which decreases risk of laryngospasm and bronchospasm Disadvantages: 1. Bradycardia is common. Circulatory failure may occur with high doses.

Remarks Either drug may be used alone. induction of general anesthesia. apnea. excellent hypnotic but does not produce significant analgesia or muscle relaxation.224 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM TABLE 14–1 Generic/Trade Name General Anesthetics (continued ) Characteristics Droperidol (Inapsine) is related to the antipsychotic agent haloperidol. General Regional and Local Anesthesia Regional or local anesthesia is usually safer than general anesthesia because it produces fewer systemic effects. the risks of anesthesia and surgery are greatly increased. An ultrashort-acting barbiturate similar to thiopental Short-acting benzodiazepine. Neuroleptanalgesia is a state of reduced awareness and reduced sensory perception during which a variety of diagnostic tests or minor surgical procedures can be done. Smaller doses are needed if other CNS depressants (eg. and other signs of CNS depression. it should be corrected before anesthesia. Neuroleptanesthesia can be used for major surgical procedures. See thiopental. If a medical disorder of a vital organ system (cardiovascular. during recovery. Consciousness returns rapidly. including dreams and hallucinations. or psychiatric disorders. produces marked analgesia. diagnostic. or therapeutic procedures. For major surgery. sedation. but they are often used together for neuroleptanalgesia and combined with nitrous oxide for neuroleptanesthesia. occurring within minutes after the drug is stopped. A rapid-acting hypnotic used with other agents in balanced anesthesia. may be given IV or IM. Innovar is a fixed-dose combination of the two drugs. Because of the risks. Rapid-acting nonbarbiturate anesthetic. For . below. and drugs are available for emergency use or cardiopulmonary resuscitation. May cause hypotension. including severity of illness. diagnostic. An opioid analgesic–anesthetic with a rapid onset and short duration of action A synthetic opioid analgesic-anesthetic related to fentanyl. amnesia. It produces sedative and antiemetic effects. Additional doses of fentanyl are often needed because its analgesic effect lasts approximately 30 minutes. presence of chronic diseases. and a lack of awareness of surroundings (called dissociative anesthesia).opioid analgesics. Hyperactivity and unpleasant dreams occur less often with children than adults. given IV by intermittent injection or by continuous infusion of a dilute solution. and transient skin rashes also may occur during recovery. unpleasant psychic symptoms may occur. it must be supplemented by other general anesthetics. and the client may require larger doses of preanesthetic sedative-type medication. the client’s physical condition. equipment. general anesthetics) are given concurrently. whereas droperidol’s effects last 3–6 hours. and the client’s mental status. Severe anxiety. respiratory. Usually given to induce anesthesia. anesthesia and major surgical procedures have profound effects on normal body functioning. It also may be used to induce anesthesia. used almost exclusively in general anesthesia. It is generally contraindicated in clients with increased intracranial pressure. it is more potent and faster acting and may allow a more rapid recovery. hypertension. severe coronary artery disease. including torsades de pointes. but respiratory depression may last 3–4 hours into the postoperative recovery period. Compared with fentanyl. awakening may require several hours. May cause respiratory depression. for example. The Food and Drug Administration recently issued a warning about serious cardiac dysrhythmias. renal) is present. apnea. when possible. anticipated duration. associated with the use of droperidol. and any other drugs being given. A single dose produces unconsciousness in less than 30 seconds and lasts 20–30 minutes. general anesthetics and neuromuscular blocking agents should be given only by people with special training in correct usage and only in locations where staff. or therapeutic procedure. may be a contraindication to regional anesthesia. Ultrashort-acting barbiturate. Given IV for conscious sedation during short endoscopic or other diagnostic procedures. immobility. hypersalivation. Given IM for preoperative sedation. It is used alone only for brief procedures. it is usually supplemented by inhalation anesthetics and muscle relaxants. vomiting. When alterations due to other disorders are also involved. If used for major surgery. Fentanyl citrate (Sublimaze) is a very potent opioid analgesic whose actions are similar to those of morphine but of shorter duration. Used most often for brief surgical. such as bronchoscopy and burn dressings. and maintenance of general anesthesia with nitrous oxide and oxygen for short surgical procedures Given by IV bolus or infusion for induction or maintenance of general anesthesia or sedation in intensive care Fentanyl and droperidol combination (Innovar) Ketamine (Ketalar) Methohexital sodium (Brevital) Midazolam (Versed) Propofol (Diprivan) Remifentanil (Ultiva) Sufentanil (Sufenta) Used for induction and maintenance of general anesthesia May be used as a primary anesthetic or an analgesic adjunct in balanced anesthesia Thiopental sodium (Pentothal) Thiopental is commonly used. death with IV administration. Recovery is rapid. General Anesthesia General anesthesia can be used for almost any surgical.

All types of surgery and brief procedures. 10–20 min and 3–5 hours with epidural administration Applied topically to skin only Related to procaine. occasionally to facilitate mechanical ventilation Adjunct to general anesthesia. recommended only for procedures expected to last 90 minutes or longer Adjunct to general anesthesia to aid endotracheal intubation and provide muscle relaxation during surgery or mechanical ventilation Adjunct to general anesthesia. formulated with epinephrine Effects occur in 1–6 min and last 1 hour Poorly water soluble Minimal systemic absorption Available in numerous preparations. below Adjunct to general anesthesia Same as vecuronium. but its potency is greater and duration of action is shorter Rapidly metabolized and less likely to cause systemic toxicity than other local anesthetics Given by injection Effects occur in 6–12 min and last 30 min A naturally occurring plant alkaloid Readily absorbed through mucous membranes A Schedule II controlled substance with high potential for abuse. Septodont) Benzocaine (Americaine) Bupivacaine (Marcaine) Regional anesthesia by infiltration. such as endoscopy and endotracheal intubation Nondepolarizing Type Atracurium (Tracrium) Cisatracurium (Nimbex) Doxacurium (Nuromax) Metocurine (Metubine) Mivacurium (Mivacron) Pancuronium (Pavulon) Intermediate acting* Intermediate acting* Long acting* Long acting. Malignant hyperthermia may occur. including aerosol sprays. earache. more potent than tubocurarine* Short acting* Long acting* Pipecuronium (Arduan) Rocuronium (Zemuron) Long acting* Intermediate acting* Tubocurarine Vecuronium (Norcuron) Long acting. hemorrhoids. and epidural anesthesia during childbirth. below Adjunct to general anesthesia Mainly during surgery after general anesthesia has been induced. effects of the drugs can be reversed by neostigmine (Prostigmin). and other conditions Articaine (Septocaine. sore throat. Butamben (Butesin) Chloroprocaine (Nesacaine) Used mainly in minor burns and skin irritations Regional anesthesia by infiltration. largely because of euphoria and other central nervous system (CNS) stimulatory effects. and epidural anesthesia Cocaine Topical anesthesia of ear. nose. skin abrasions. It is not used for spinal anesthesia. produces psychic dependence and tolerance with prolonged use Too toxic for systemic use Effects occur in 1–5 min and last 30–60 min May cause local allergic reactions Effects occur in <15 min and last 3–4 hours Clinical Uses Local infiltration and nerve block for dental and periodontal procedures or oral surgery Topical anesthesia of skin and mucous membrane to relieve pain and itching of sunburn. nerve block. the prototype of nondepolarizing drugs* Intermediate acting* Adjunct to general anesthesia Same as rocuronium. and ointments May cause allergic reactions Effects occur in 5 min or less and last 15–45 min Given by injection May cause systemic toxicity Effects occur in 5 min and last 2–4 hours with injection. rectal suppositories. and throat Dibucaine (Nupercainal) Topical anesthesia of skin and mucous membranes (continued ) . TABLE 14–3 Generic/Trade Name Local Anesthetics Characteristics Newer drug.CHAPTER 14 ANESTHETICS 225 TABLE 14–2 Generic/Trade Name Neuromuscular Blocking Agents (Skeletal Muscle Relaxants) Characteristics Uses Depolarizing Type Succinylcholine (Anectine) Short acting after single dose. other minor burns and wounds. nerve block. occasionally to aid endotracheal intubation or mechanical ventilation Adjunct to general anesthesia. action can be prolonged by repeated injections or continuous intravenous infusion. to facilitate endotracheal intubation and mechanical ventilation *All the nondepolarizing agents may cause hypotension. throat lozenges. lotions.

needle placement must be verified by aspirat- . Local anesthetics should be injected only by people with special training in correct usage and only in locations where staff. effects occur in 5–15 min and last 1–3 hours With topical use. effects occur in 2–5 min and last 15–45 min Formulated to be absorbed through intact skin. effects occur in <2 min and last 60 min Epidurally.5% and prilocaine 2. Guidelines for injections of local anesthetic agents include the following: 1. longer duration. effects occur in 5–15 min and last 1–3 hours Rarely used Rapidly metabolized With injection. Lidocaine. spinal. effects occur in 3–5 min and last 0. one of the most widely used. dermatoses. 3. local anesthetic solutions must not be injected into blood vessels because of the high risk of serious adverse reactions involving the cardiovascular system and CNS. To prevent accidental injection into a blood vessel. nerve block. equipment. spinal anesthesia is often the anesthesia of choice for surgery involving the lower abdomen and lower extremities. hemorrhoids. effects occur in <2 min and last 30–60 min With epidural use. and less toxicity because it is more rapidly metabolized and excreted With injection. Choice of a local anesthetic depends mainly on the reason for use or the type of regional anesthesia desired. action slower in onset and longer in duration than lidocaine With injection. contraindicated for use on mucous membranes or abraded skin Must be applied at least 1 hour before the planned procedure Effects occur in 1–2 hours and last 1–2 hours Related to lidocaine. the patches are to be applied for 12 hours daily only. nerve block. Proparacaine (Alcaine) Ropivacaine (Naropin) Topical anesthesia of the eye for tonometry and for removal of sutures. Except with IV lidocaine for cardiac dysrhythmias. and epidural infusion Prilocaine (Citanest) Procaine (Novocain) Regional anesthesia by infiltration. and epidural anesthesia Pramoxine (Tronothane) Topical anesthesia for skin wounds. effects occur in 5–15 min and last 1–3 hours Not injected or applied to nasal mucosa because it irritates tissues Effects occur in 3–5 min Similar to lidocaine in effectiveness but has a slower onset. and spinal anesthesia. sigmoidoscopy Regional anesthesia by infiltration. nerve block. effects occur in 2–5 min and last 15–60 min Causes minimal irritation of the eye but may cause allergic contact dermatitis of the fingers Given by injection or epidural infusion With epidural infusion. nerve block. Not used topically. (Warning: Do not use preparations containing epinephrine for dysrhythmias. effects occur in 10–30 min and last up to 6 hours Applied topically Formerly injected for regional anesthesia but now rarely injected because of possible allergic reactions Clinical Uses Topical anesthesia in otolaryngology Local or regional anesthesia for surgery and obstetrics and for postoperative pain management Lidocaine (Xylocaine) Topical anesthesia and regional anesthesia by local infiltration.75–1. foreign bodies.5% (EMLA) Topical anesthesia for vaccinations or venipunctures in children Mepivacaine (Carbocaine) Infiltration. effects occur within 10 min and last about 8 hours Given topically and by injection One of the most widely used local anesthetic drugs Topical patches are available for the relief of painful conditions such as postherpetic neuralgia. and drugs are available for emergency use or cardiopulmonary resuscitation. and epidural anesthesia Intravenously to prevent or treat cardiac dysrhythmias (see Chap. especially in people who are elderly or have chronic lung disease. 52). and cataracts Obstetric or postoperative analgesia and local or regional surgical anesthesia Topical anesthesia Tetracaine (Pontocaine) example. 2. endotracheal intubation. Acts as an antidysrhythmic drug by decreasing myocardial irritability With injection.5 hours Epidurally.) Lidocaine 2. A major advantage of spinal anesthesia is that it causes less CNS and respiratory depression. is available in topical and injectable forms.226 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM TABLE 14–3 Generic/Trade Name Dyclonine (Dyclone) Levobupivacaine (Chirocaine) Local Anesthetics (continued ) Characteristics Absorbed through skin and mucous membranes Effects occur in <10 min and last <60 min Newer drug May be given by local infiltration and epidurally When given epidurally.

You have been asked to extend your shift because someone has called in sick. • Explain the expected course of events of the perioperative period (eg. you realize that you administered it to the wrong patient. Ask about drug allergies. those high in protein. • Assess use of prescription and nonprescription drugs. Assess for risk factors for complications of anesthesia and surgery (cigarette smoking. cough. ask if the client has ever had an allergic reaction to a local anesthetic. and laboratory and other data. Nursing Diagnoses • Risk for Injury: Trauma related to impaired sensory perception and impaired physical mobility from anesthetic or sedative drugs . you are interrupted twice. and ginseng can increase risks of bleeding. amount. • Continue to assess vital signs. • Use sterile technique in wound care. renal. coughing and deep-breathing exercises. If use of local or regional anesthesia is anticipated. and stroke. feverfew. and other data as indicated to establish baseline measurements for monitoring changes. and electrolytes to promote healing). specific preparations for surgery. Specific interventions include: • Observe and record vital signs. respiratory. Assess vital signs. other medications. • Explain how postoperative pain will be managed. hypovolemia or hypervolemia). maintaining fluid balance and urine output). wound infection). • Ask about the use of herbal drugs during the previous week. then periodically until discharge. and degree of anxiety and fear. ambulate. Some guidelines include the following: • Provide foods and fluids to improve or maintain nutritional status (eg. hypertension. • Initiate discharge planning for a smooth transition to home care. This helps promote respiratory and cardiovascular function and decreases anxiety. chronic cardiovascular. • Help the client to turn. respiratory and cardiovascular status. • Risk for Injury: CNS depression with premedications and general anesthetics • Pain related to operative procedure • Decreased Cardiac Output related to effects of anesthetics. You are preparing some intravenous morphine to administer to one patient. exercise legs. obesity. level of consciousness. approximate length of stay). The client will: • Receive sufficient emotional support and instruction to facilitate a smooth preoperative and postoperative course • Be protected from injury and complications while selfcare ability is impaired • Have emergency supplies and personnel available if needed • Have postoperative discomfort managed appropriately Interventions Preoperatively. deep breathe. fluid and electrolyte imbalance. but before you administer the morphine. If potential problems are identified (eg. • Assess for signs of complications (eg. Monitor the site. ephedra increases risks of cardiac dysrhythmias. especially those taken within the past 3 days. • Assist clients with measures to facilitate recovery postoperatively (eg. assist the client to achieve optimal conditions for surgery. caring for two patients recovering from general anesthesia. respiratory problems. vitamin C and other vitamins. Assess ability and willingness to participate in postoperative activities to promote recovery. • • • • • Postoperative Assessment • During the immediate postoperative period. • Maintain IV infusions. ginkgo. wound status. or other disease processes). laboratory data.CHAPTER 14 ANESTHETICS 227 How Can You Avoid This Medication Error? You are working in a busy postanesthesia recovery unit (PACU). Effects of anesthetics and adjunctive medications persist into postanesthesia recovery. especially those that are likely to cause perioperative complications. garlic. • Give pain medication appropriately as indicated by the client’s condition. the major focus is on maintaining a safe environment and vital functions. attitude toward anesthesia and surgery. leg exercises and early ambulation. After you finally administer the drug. myocardial infarction. when feasible. and surgery • Risk for Ineffective Breathing Patterns related to respiratory depression • Anxiety or Fear related to anticipated surgery and possible outcomes Planning/Goals Nursing Process Preoperative Assessment • Assess nutritional status. intervene to prevent them from becoming actual problems. limited exercise or activity. This is often a major source of anxiety. For example. and elimination frequently until sensory and motor functions return. and perform other self-care activities until he or she can perform them independently. and type of fluids. thrombophlebitis. close observation and monitoring during postanesthesia recovery. assess vital signs and respiratory and cardiovascular function every 5 to 15 minutes until reactive and stabilizing. • Help the client maintain exercise and activity. Postoperatively. fluid balance. kava and valerian can increase effects of sedatives. Assess the client’s understanding of the intended procedure.

sedation. The American Society of Anesthesiologists recommends that all herbal products be stopped two or three weeks before any surgical procedure. 4. increased movement. These drugs should not be used in clients with severe cardiovascular disease or hyperthyroidism. local anesthetics may cause fetal bradycardia. Because few studies and little testing have been done. and St. • Observe for improved ability in self-care activities. and the surgical procedures themselves. or after surgery. decreased intensity of uterine contractions. This combination should not be given IV or in excessive dosage because the local anesthetic and epinephrine can cause serious systemic toxicity. laryngeal. ears. or urethral mucosa. ginseng. If excessive amounts are used (eg. affect blood pressure or heart rhythm. Such activities can lead to injuries. you will receive pain medication by injection (often intravenously) for 2 or 3 days. CLIENT TEACHING GUIDELINES Perioperative Medications ✔ When anticipating a surgical procedure and a general anesthetic.000 because of the danger of producing vasoconstriction in uterine blood vessels. others recommend stopping most products two or three days before surgery. movement. ✔ Follow instructions and try to cooperate with health care personnel in activities to prevent postoperative complications. d. c. tracheal. echinacea. toes. and prolonged labor. Instructions about postoperative activities vary with the type of surgery. the concentration of epinephrine should be no greater than 1:200. . gingko. oral. ephedra. bronchial. John’s wort) can interfere with or increase the effects of some drugs. Local anesthetics given during labor cross the placenta and may depress muscle strength. 6. Severe ventricular dysrhythmias may result. feverfew. If blood is aspirated into the syringe. coughing and deep breathing. no fever or other signs of infection). ✔ With preanesthetic. other medications given before. valerian. gers. during. In most instances. 5. such as the following: a. garlic. another injection site must be selected. The drugs are well absorbed through mucous membranes and may cause systemic adverse reactions. be sure to inform health care providers about any herbal or other dietary supplements you take. use only local anesthetic solutions that have been specifically prepared for spinal anesthesia and are in single-dose containers. muscle tone. e. kava. sedative-type medications. Most of the commonly used herbal products (eg. then by mouth. local anesthetics should be given in the lowest effective dosage. • The client states that pain has been managed satisfactorily. including respiratory and wound infections. do not eat. If used in obstetrics. in paracervical block). take enough pain medication to allow ambulation. This combination of drugs should not be used for nerve blocks in areas supplied by end arteries (fin- b. stay in bed with the siderails up and use the call light if help is needed. Such vasoconstriction may cause decreased placental circulation. ing before injecting the local anesthetic solution. or increase risks of bleeding. ask how pain will be managed after surgery and what you will need to do to promote recovery. penis) because it may produce ischemia and gangrene. chew. ✔ If having surgery. This combination should not be used with inhalation anesthetic agents that increase myocardial sensitivity to catecholamines. ✔ After surgery. and rooting behavior in the newborn. Topical Anesthesia of Mucous Membranes When used to anesthetize nasal. Such solutions require special safety precautions. ✔ Do not try to perform activities requiring mental alertness and physical coordination while drowsy or less than alert from general anesthesia. Multiple-dose containers are not used because of the risk of injecting contaminated solutions. ✔ After a local anesthetic is injected for dental or other oral surgery procedures. Apgar scores are usually normal. and other exercises to promote recovery. Dosage used for spinal anesthesia during labor is too small to depress the fetus or the newborn.228 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Evaluation • Observe for absence of injury and complications (eg. Epinephrine is often added to local anesthetic solutions to prolong anesthetic effects. or drink hot liquids until the anesthetic has completely worn off. pharyngeal. You may fall or otherwise injure yourself if you get out of bed without assistance. For spinal or epidural anesthesia. or pain medication. and expulsion of meconium before birth and marked depression after birth. some products have unknown effects when combined with anesthetics. including cardiac dysrhythmias. nose.

cystic fibrosis. the formulation now contains an antimicrobial agent. infants and children have a higher anesthetic requirement. Thus. 3. and after surgical or other procedures that require anesthesia or sedation must be skilled in using the nursing process with children. Dosages in children . skin rash. Slow titration of dosage. although children are less likely than adults to have ventricular dysrhythmias. bronchospasm. hypotension. 1. full stomach) and for intramuscular administration when a suitable vein is unavailable. Local irritation. For the drugs to be effective. 8. This precaution stems from reports of several deaths associated with the use of succinylcholine in children with previously undiagnosed skeletal muscle myopathy. aspiration) and death from anesthesia. laryngospasm. For example. and they cannot be used effectively and safely on other body parts. another type of local anesthetic can usually be substituted safely. elective surgery in children and adolescents. and tetracaine have not been established in children younger than 12 years of age. contraindications to a particular agent. or nausea. Adverse effects include respiratory depression. than healthy adults. 2. or other bronchospastic disorders. Safety and efficacy of bupivacaine. a newer agent. In addition. However. features that make it especially useful for children with asthma. ✔ With spray preparations. However. a rapid metabolism rate. is now contraindicated for routine. Use in Children Compared with adults. they must have direct contact with the affected area. In addition. so it may not be indicated in clients who already have increased intracranial pressure or mass lesions. or store near any heat source. This seems to reduce anxiety for both parents and children. mivacurium) are commonly used. relative to size and weight. ✔ Use local anesthetic preparations for only a short period. but if they have occurred. formerly a commonly used agent. atracurium. intermediate-acting nondepolarizing agents (eg. the nurse who cares for a child before. and slow drug injection into a rapidly flowing IV can minimize these effects. the presence of client conditions that affect or preclude use of a particular drug. Halothane may also sensitize the myocardium to epinephrine. it is much more expensive than halothane. and pain with injection. and the preference of the anesthesiologist. ✔ Use the drug only for the condition for which it was prescribed. It also decreases cerebral blood flow and intracranial pressure. and a smooth emergence with little mental confusion. Local anesthetics usually have the same uses. It allows a faster induction and emergence. Allergic reactions are rare. making it useful in neurosurgery. It has a rapid onset. In addition. precautions. whoever administers anesthetics to children should be knowledgeable about anesthetics and their effects in children. Some agencies allow parents to be present during induction of general anesthesia. With muscle relaxants. and produces a minimal increase in intracranial pressure. report the condition to the physician. It causes bronchodilation and does not irritate respiratory mucosa. adding lidocaine. Halothane has been commonly used. If the condition for which it is being used persists. sedation. spray near food. do not inhale vapors. Children are more likely to have postoperative nausea and vomiting than adults. during. 4. Propofol may be given by injection for induction and an IV infusion pump for maintenance of anesthesia or sedation. and hives can develop. Succinylcholine. and adverse effects in children as in adults. the drug dilates blood vessels in the brain and increases intracranial pressure. For short surgical procedures. ✔ Apply local anesthetics to clean areas. dyclonine. laryngospasm. which should reduce risks of infection. may have some advantages over halothane in pediatric anesthesia. Sevoflurane. 6. the choice depends on the type of surgery and anesthesia. propofol is widely used for sedation with diagnostic tests or special procedures that require children to be sedated and immobile. Benzocaine should not be used in infants younger than 1 year of age. Propofol is approved for use in children 3 years of age and older. a large-bore IV catheter. succinylcholine is still indicated in children who require emergency intubation or rapid securing of the airway (eg. children are at greater risk of complications (eg. ✔ Do not apply more often than directed. Most preparations are specifically made to apply on certain areas. In general. does not stimulate the sympathetic nervous system or potentiate cardiac dysrhythmias. However. 5.CHAPTER 14 ANESTHETICS 229 CLIENT TEACHING GUIDELINES Topical Anesthetics ✔ Use the drug preparation only on the part of the body for which it was prescribed. 7. a local anesthetic prescribed to relieve itching may aggravate an open wound. ✔ Inform dentists or other physicians if allergic to any local anesthetic drug.

and the liver’s ability to metabolize other drugs may be impaired. Because cardiovascular homeostatic mechanisms are often impaired. However. there is greater systemic absorption and risk of toxicity in infants. In addition. With injections of a local anesthetic. Succinylcholine is also metabolized in the liver and should be used very cautiously in clients with hepatic impairment. With atracurium. heart block. The drugs should be used cautiously. neuromuscular blocking agents. Most neuromuscular blocking agents are metabolized or excreted in urine to varying extents. neuromuscular blocking agents. liver metabolism produces active metabolites. in minimally effective doses. clients receiving other CNS depressant drugs (eg. These drugs are readily absorbed through mucous membranes and may cause systemic toxicity. and clients awaken within a few minutes of stopping drug administration. are more likely to reach high plasma levels and cause systemic toxicity in clients with hepatic disease. the level of sedation may be adjusted to the client’s condition and needs. the rate should be slower in older adults. rocuronium. The drugs should be used very cautiously in clients with renal impairment. and critically ill clients. As a general rule. which are then excreted by the kidneys. clients with severe hepatic impairment are more likely to acquire toxic plasma concentrations of lidocaine and prilocaine from topical use of EMLA because of impaired ability to metabolize the drug. and physical condition. However. Propofol clearance may be slower because of decreased hepatic blood flow. low concentrations of local anesthetics should be used. Propofol Use in Renal Impairment Most inhalation general anesthetic agents can be used in clients with renal impairment because they are eliminated mainly by exhalation from the lungs. renal impairment may lead to accumulation of neuromuscular blocking agents or their metabolites. With succinylcholine. Use in Older Adults Older adults often have physiologic changes and pathologic conditions that make them more susceptible to adverse effects of anesthetics. and urine volume. In addition. all general anesthetics reduce blood flow to the liver. metabolism of atracurium produces a metabolite (laudanosine) that accumulates in renal failure and may cause neurotoxicity. . For example. and several may accumulate in the presence of renal impairment because of delayed elimination. provide local anesthesia. older adults may be at risk for decreased cardiac output. With topical applications to intact skin. including cardiopulmonary resuscitation and airway management. glomerular filtration. These drugs should be administered and monitored only by health care personnel who are skilled in the management of critically ill clients. Propofol is metabolized mainly in the liver to inactive metabolites. For topical application to mucous membranes. Propofol is an anesthetic used in subanesthetic doses for short-term sedation of clients who are intubated and mechanically ventilated. Neuromuscular blocking agents vary in the extent to which they are metabolized in the liver. short-term use of bolus doses does not impair renal function. It is given by continuous IV infusion in doses of 5 to 50 mcg/kg/min. some of which are excreted through the kidneys. The cream is applied at the injection site with an occlusive dressing at least 60 minutes before vaccination or venipuncture. delayed excretion and a longer halflife lead to higher peak plasma levels. renal effects vary among the drugs. and oxygen desaturation if dosage is not reduced.230 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM should be reduced according to age. Long-term infusion may result in accumulation in body fat and prolonged elimination. as do IV general anesthetics. and vecuronium are eliminated mainly by the liver. repeated doses may cause accumulation of the drug or its metabolites and increased risks of adverse effects. and cardiac arrest. however. hypotension. which are metabolized primarily in the liver. A mixture of lidocaine and prilocaine (Eutectic Mixture of Local Anesthetics [EMLA]) was formulated to penetrate intact skin. body weight. Higher plasma levels can cause hypotension. With local anesthetics. lower doses of these agents are usually needed. With long-term infusion. apnea. airway obstruction. These metabolites can accumulate and cause hyperkalemia in clients with renal impairment. Thus. and adjunctive medications. opioids or benzodiazepines). Use in Hepatic Impairment Most inhalation general anesthetics are minimally metabolized in the liver and therefore are unlikely to accumulate with short-term usage. such as a lighter level during visiting hours or a deeper level during painful procedures. and decrease pain of vaccinations and venipuncture. The rate of infusion should be individualized and titrated to clinical response. Use in Critical Illness Propofol. and local anesthetics are commonly used in intensive care units. Doses can be increased in small amounts every 5 to 10 minutes to achieve sedation and decreased in small amounts every 5 to 10 minutes to allow awakening. It has a rapid onset of action. injections of the amide type (eg. in such clients. Critical care nurses must often care for clients receiving IV infusions of the drugs and titrate dosage and flow rate to achieve desired effects and minimize adverse effects. With propofol. They may accumulate with hepatic impairment because of delayed elimination. EMLA cream should not be used on mucous membranes (or abraded skin). atracurium. Thus. which is mainly metabolized by the liver with a small amount excreted unchanged in urine. lidocaine). they reduce renal blood flow. Thus.

The most commonly used are the nondepolarizing agents (eg. 1. agitation. prolong muscle weakness. pneumonia. and other measurements are needed. If a combination of injectable preanesthetic medications is ordered. Reduced doses are indicated to decrease adverse effects. The drug can irritate peripheral veins. arterial blood gas levels. or one of the drugs may be inactivated or altered when combined. which are given by intermittent bolus or continuous infusion. Clients requiring prolonged use of neuromuscular blocking agents usually have life-threatening illnesses such as adult respiratory distress syndrome. Repeated doses may cause accumulation of the drug or its metabolites or slow its metabolism. It also has antiemetic properties. vital functions need to be assessed and monitored at regular intervals. muscle wasting. If they are given too late. so analgesia must be provided for patients in pain or those having painful procedures. systemic inflammatory response syndrome. vital signs. especially those with impaired cardiovascular function such as dysrhythmias. and make weaning from a ventilator more difficult. For example. Timing is important. some clinicians recommend that its use be limited to 24 to 48 hours. the client may be sedated longer than necessary. c. the drugs may accumulate. Local anesthetics should be used with caution in critically ill clients. b. dentists. Approximately 1. Although larger amounts are sometimes given. When the drugs are used for extended periods. pulmonary capillary wedge pressures. If compatibility is unknown. After assessment. An infusion pump is required for accurate administration and dosage titration. Do not mix the drugs. During propofol infusion. and malnutrition. electrocardiograms. If they are given too early. NURSING ACTIONS NURSING ACTIONS Anesthetic Drugs RATIONALE/EXPLANATION Drug administration in relation to anesthesia refers primarily to preanesthetic or postanesthetic drugs because physicians. the dose is increased until the desired level of sedation occurs. the client may suffer needless anxiety and not be relaxed and drowsy when anesthesia is being initiated. do not mix in the same syringe and give as one injection unless the drugs are known to be compatible and the total volume is approximately 2 mL. Because propofol is expensive. critical care nurses may administer propofol or a neuromuscular blocking agent to patients being mechanically ventilated. atracurium. probably no more than 2 to 3 mL should be given intramuscularly (IM) for both drug absorption and client comfort.25 mL (20 minims) is the upper limit for subcutaneous injections. oxygen saturation. if a local anesthetic (eg. lidocaine is often given in coronary care units to decrease myocardial irritability and prevent or treat ventricular tachydysrhythmias (see Chap. In addition. medication effects may wear off before induction of anesthesia. Schedule the administration of preanesthetic medications so that their peak effects are reached at the optimal time. and nurse anesthetists administer anesthetic drugs. Accumulation results mainly from delayed elimination. and the client may or may not become sedated before being transported to the surgery suite. and treat status epilepticus. control increased intracranial pressure. if possible. Preanesthetic medications are often ordered “on call” rather than for a specific time. dosage of both agents must be reduced to decrease risks of respiratory arrest. In addition to usual uses of local anesthetics. With propofol intravenous (IV) infusion: (1) Administer through a central or large peripheral IV catheter. The drug should not be stopped because rapid awakening may be accompanied by anxiety. It is better if these medications are administered so that peak sedative effects occur before administration of anesthetics to avoid excessive central nervous system (CNS) depression. or multiple organ dysfunction syndrome. Administer accurately a.CHAPTER 14 ANESTHETICS 231 lacks analgesic effects. give two or more injections if necessary. fentanyl). Also. and resistance to mechanical ventilation. clients are at risk for development of complications of immobility such as atelectasis. bupivacaine) is infused epidurally with an opioid analgesic (eg. In addition. For neurologic assessment. Neuromuscular blocking agents are used to facilitate mechanical ventilation. For hemodynamic and respiratory assessment. (continued ) . heart block. hypotension. or shock. and the risk of postanesthetic respiratory and circulatory complications is increased. atropine and glycopyrrolate (Robinul) are compatible with morphine. 52). dosage is decreased every 12 or 24 hours to maintain light sedation. vecuronium). A precipitate may develop. with an infusion pump.

the nurse often assists by obtaining and perhaps holding the drug vial while the physician aspirates drug solution into a syringe. and arousability for neurologic assessment when drug dosage is reduced by slowing the IV infusion rate. For example. show the drug container to the physician and verbally verify the name of the drug. observe for: (1) Excessive sedation—delayed awakening. hypotension. be certain to use the appropriate preparation of the prescribed drug. and respiratory failure. detect. e. lactated Ringer’s. observe for relief of the symptom for which the drug was ordered. Most preparations are used in particular conditions or bodily locations. These drugs can cause cardiovascular collapse. f. and whether the solution is plain or contains epinephrine. drowsiness. Observe for therapeutic effects a. Accuracy of administration is essential so that adverse reactions can be avoided or treated appropriately if they do occur. and 5% dextrose and 0. c. Although the physician is responsible for drugs he or she administers. the percentage concentration. observe for relaxation. Therapeutic effects depend on the type of drug and the reason for use. Relief is usually obtained within a few minutes. and itching of hemorrhoids. these effects are usually evident within 20 to 30 minutes after the drugs are given. RATIONALE/EXPLANATION Propofol is an emulsion that is incompatible with other drugs. observe for excessive sedation. and movement. Also. If assisting a physician in injecting a local anesthetic solution. observe for lack of agitation and movement. The nurse observes for adverse effects in the preanesthetic and postanesthetic periods.45% sodium chloride. responsiveness. Have drugs and equipment for resuscitation readily available in any location where propofol. When applying local anesthetics for topical or surface anesthesia. When adjunctive drugs are given for preanesthetic medication.2% sodium chloride IV solutions (5) Change IV tubing and propofol solution every 6 hours if manufactured IV solution is not used. failure to respond to verbal or tactile stimuli . Manufacturer’s recommendation Strict aseptic administration and maintenance techniques are needed because of the potential for microbial contamination. 2. or local anesthetics are being used. When a neuromuscular blocking agent is used in an intensive care unit. Ask the client if the symptom has been relieved. and relief of pain. (3) Dilute with 5% dextrose injection and do not dilute to a concentration of <2 mg/mL. Other preparations are used only on the skin. With preanesthetic drugs. When propofol is used for sedation in an intensive care unit. tolerance of mechanical ventilation. After general anesthesia and during propofol administration in intensive care units. adverse reactions to epinephrine may occur. and other problems.232 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM NURSING ACTIONS (2) Do not mix with other drugs before administration. cardiac dysrhythmias. pain in skin or mucous membrane. When local anesthetic drugs are applied for surface anesthesia. or treat hypoxia. (continued ) a. If manufactured solution is used and the nurse only has to access the bag of fluid. (4) Propofol is compatible with 5% dextrose. assess the situation to determine whether further action is needed. such as sore mouth or throat. The often-used combination of an opioid analgesic and a sedativetype drug produces additive CNS depression. 3. d. and if not. change IV tubing every 12 hours. observe for tolerance of mechanical ventilation. Depending on dose and client condition. b. the anesthesiologist monitors the client’s condition constantly to prevent. Observe for adverse effects Serious adverse effects are most likely to occur during and within a few hours after general anesthesia and major surgery. d. The early recovery period is normally marked by a progressive increase in alertness. neuromuscular blocking agents. b. hypotension. lidocaine viscous is used only as an oral preparation for anesthesia of the mouth and throat. 5% dextrose and 0. lactated Ringer’s and 5% dextrose. During general anesthesia. The incidence of adverse reactions increases with the amount and concentration of local anesthetic solution injected.

For interactions involving preanesthetic medications. hypoxia. Additive hypotension may occur during and after surgery because of adrenocortical atrophy and reduced ability to respond to stress. These symptoms are more likely to occur with large doses. and Opioid Analgesics and Opioid Antagonists (Chap. others are used mainly for other purposes. Headache is more likely to occur if the person does not lie flat for 8 to 12 hours after spinal anesthesia is given. 6). These problems are most likely to occur while general anesthesia is being administered and progressively less likely as the patient recovers or awakens. Restlessness may be caused by the anesthetic. CNS depressants include many different drug groups and hundreds of individual drugs. nausea. Extreme caution must be used to prevent excessive CNS depression. arrhythmias (3) Headache and urinary retention with spinal anesthesia 4. Anticholinergic Drugs (Chap. Doses used for spinal or epidural anesthesia usually have little effect on cardiovascular function. 21). injections into highly vascular areas. Increased likelihood of cardiac arrhythmias. excitement. unpleasant dreams or hallucinations also may occur. if caused by hypoxia but interpreted as being caused by pain. and circulatory failure may occur. When they are combined with general anesthetics. antianxiety agents. c. tachycardia and other cardiac arrhythmias. observe for: (1) CNS stimulation at first (hyperactivity. in decreasing doses. Any combination of these drugs with each other or with general anesthetic agents produces additive CNS depression. administration of analgesics would aggravate hypoxia. isoproterenol. sedative-hypnotics (5) Corticosteroids . Additive hypotension. prolonged paralysis of respiratory muscles with muscle relaxant drugs. norepinephrine (4) CNS depressants—alcohol. or hypoxia and should be assessed carefully before action is taken. Drugs that increase effects of general anesthetic agents: (1) Antibiotics—aminoglycosides (gentamicin and related drugs) (2) Antihypertensives (3) Catecholamines—dopamine. With ketamine. and vomiting. or retention of respiratory tract secretions due to a depressed cough reflex. shock. antihistamines. see Antianxiety and Sedative-Hypnotics Drugs (Chap. antipsychotics. Vital signs are often unstable during the early recovery period and therefore need to be checked frequently. pain. fluid and electrolyte imbalances (4) Other problems—restlessness. If they are combined. hypercarbia RATIONALE/EXPLANATION Laryngospasm may occur after removal of the endotracheal tube used to administer general anesthesia. These effects are most likely to occur with high doses. Hypoxia and hypercarbia indicate inadequate ventilation and may result from depression of the respiratory center in the medulla oblongata. anticonvulsants. epinephrine. For example. Urinary retention may occur in anyone but is more likely in older men with enlarged prostate glands. Halothane and a few rarely used general anesthetics sensitize the myocardium to the effects of catecholamines. barbiturates. most physicians recommend administration of hydrocortisone before. For clients who have been receiving corticosteroids. opioid analgesics. and. These antibiotics inhibit neuromuscular transmission. ventricular tachycardia or ventricular fibrillation may occur. 8).CHAPTER 14 ANESTHETICS 233 NURSING ACTIONS (2) Respiratory problems—laryngospasm. after surgery. Local anesthetics depress myocardial contractility and the cardiac conduction system. Observe for drug interactions a. Extreme changes must be reported to the surgeon or the anesthesiologist. and CNS depression is a side effect. Some are used therapeutically for their CNS depressant effects. antidepressants. seizure activity) followed by CNS depression (2) Cardiovascular depression—hypotension. or accidental injection into a blood vessel. during. After regional anesthesia. (continued ) (3) Cardiovascular problems—hypotension. high concentrations. additive muscle relaxation occurs with increased likelihood of respiratory paralysis and apnea. Such a combination is contraindicated.

Additive muscle relaxation Drugs that produce hypokalemia potentiate skeletal muscle relaxants Additive muscle relaxation (2) General anesthetics (3) Thiazide diuretics (eg. and other problems develop. This drug may be given to treat acute convulsions resulting from toxicity of local anesthetic drugs. Drugs that increase effects of neuromuscular blocking agents (muscle relaxants): (1) Aminoglycoside antibiotics (eg. When clients are excessively depressed and hypotension. additive blockade and increased risk of respiratory depression and apnea occur. If given with other blocking agents. (4) Succinylcholine (Anectine) d. and acute ingestion has an additive CNS depressant effect with general anesthetic agents. that is. With chronic ingestion. If overdosage of local anesthetics occurs. tranylcypromine.234 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM NURSING ACTIONS (6) Monoamine oxidase (MAO) inhibitors—isocarboxazid. magnesium sulfate. Although they may be given spinal anesthesia. larger amounts of general anesthetic agents are required in clients who have acquired tolerance to alcohol. in clients with hyperthyroidism or severe heart disease or those receiving adrenergic blocking agents for hypertension. procainamide. verapamil) (continued ) . lithium. quinidine. Additive relaxation of skeletal muscles. Effects of general inhalation anesthetics decrease rapidly once administration is discontinued. gentamicin) These drugs can cause neuromuscular blockade on their own. propranolol (Inderal) (2) CNS depressants (3) Epinephrine Additive depression and increased risk of hypotension and arrhythmias Additive CNS depression with high doses Epinephrine is often used in dental anesthesia to prolong anesthetic effects by delaying systemic absorption of the local anesthetic drug. hydrochlorothiazide) (4) Others (clindamycin. procarbazine. These drugs should be discontinued at least 10 days to 3 weeks before elective surgery. cardiac dysrhythmias. tolerance to the effects of alcohol and general anesthetics develops. respiratory depression. Apnea may be prolonged by the combination of a local anesthetic agent and succinylcholine. Alcohol is a CNS depressant. Drugs that increase effects of local anesthetics: (1) Cardiovascular depressants—general anesthetics. These are seldom necessary or desirable. others RATIONALE/EXPLANATION Additive CNS depression. Drugs that decrease effects of local anesthetics: (1) Succinylcholine (Anectine) e. treatment is mainly symptomatic and supportive. Drugs that decrease effects of general anesthetics: (1) Alcohol (2) Atropine c. which may occur with general inhalation anesthetics. clients taking MAO inhibitors should not be given general anesthesia. They should not be given local anesthetic solutions to which epinephrine has been added. the main treatment is stopping the anesthetic and supporting vital functions rather than giving additional drugs. Atropine is often given as preanesthetic medication to prevent reflex bradycardia. however. (7) Neuromuscular blocking agents b. Effects of IV anesthetics decrease more slowly. however. It is contraindicated for this use. If emergency surgery is required. These drugs are given for this therapeutic effect so that smaller amounts of general anesthetics may be given. there is increased risk of hypotension. Few drugs actually decrease effects of general anesthetics. isoniazid.

phenytoin) How Can You Avoid This Medication Error? Answer: The risk of administering a drug to the wrong patient is increased in the PACU because patients are unconscious and patient turnover is frequent. A. D. 208–216. A post hoc descriptive study of patients receiving propofol. Saunders. (2) Enzyme inducers (eg. what are important factors to consider? . Hadbavny. Textbook of medical physiology. Textbook of critical care. Fetrow. Philadelphia: W. (Updated monthly). B. 5. Shoemaker (Eds. Sedatives and analgesics in critical care. Philadelphia: W. or after general anesthesia. E. These drugs may increase metabolism of neuromuscular blocking agents so that drug onset of action is delayed and duration of action is shorter. Holbrook & W. 286(2). (2001). A. 8(1). PA: Springhouse Corporation. Kowalski. Moss. M. What interventions are needed to ensure client safety during recovery from general anesthesia? 4.CHAPTER 14 ANESTHETICS 235 NURSING ACTIONS f. S. M. Drugs that decrease effects of neuromuscular blocking agents: (1) Anticholinesterase drugs (eg.. W. Journal of the American Medical Association. R. K. or after local or regional anesthesia. (2000). during. Herbal medicines and perioperative care. & Avila. & Yuan. When assessing a client before. (1999). M. J. In A. When assessing a client before. 4th ed. 507–513. Review and Application Exercises 1. Springhouse. A. C.). & Rayfield. J. S. P. American Journal of Critical Care. C. They do not reverse the effects of succinylcholine and may potentiate them instead. 961–971. C. Saunders. neostigmine) RATIONALE/EXPLANATION These drugs often are used to reverse the effects of the nondepolarizing agents.. S. Grenvik. (1999). W. & Hoyt. What interventions are needed to ensure client safety during recovery from local or regional anesthesia? 7. Other factors that could have contributed to the error include the length of time the nurse had worked (fatigue) and the interruptions that distracted her concentration. Guyton. J. carbamazepine. Professional’s handbook of complementary & alternative medicines. What are major adverse effects of local anesthetic agents? 6. St. Ayres. What are the main elements of drug administration and client assessment when propofol or a neuromuscular blocking agent is used in critical care settings? SELECTED REFERENCES Ang-Lee. B. during. it is essential that the patient is properly identified using the name band and the orders verified on the patient’s chart. Louis: Facts and Comparisons. 10th ed.. C. In these situations. what are important factors to consider? 2. What are major adverse effects of general anesthetics and neuromuscular blocking agents? 3. C. pp. J. (2000). Drug facts and comparisons. & Hall. R.

Reflect on: ᮣ Prioritize your assessment when you reach the intoxicated youth. his friend drank over half a bottle of vodka and no one has been able to wake him up. cocaine. These include prescription and nonprescription and legal and illegal drugs. DEPENDENCE Characteristics of drug dependence include craving a drug. cocaine. per- . ᮣ List factors. compulsive drug-seeking behavior. This means that the body adjusts to the drugs so that higher doses are needed to achieve feelings of pleasure or stave off withdrawal symptoms. 5. Compare and contrast characteristics of dependence associated with alcohol. marijuana. Describe specific antidotes for overdoses of central nervous system (CNS) depressant drugs and the circumstances indicating their use. These feelings. ethanol. SUBSTANCE ABUSE buse of alcohol and other drugs is a significant health. antianxiety/ sedative-hypnotic agents. 6. often with unsuccessful attempts to decrease its use. alcohol. As used in this chapter. Critical Thinking Scenario You are a school nurse working in a middle school. benzodiazepines. THE STUDENT WILL BE ABLE TO: 1. physical dependence (withdrawal symptoms if drug use is stopped). and legal problem. traumatic injury. cocaine.chapter 15 Substance Abuse Disorders Objectives AFTER STUDYING THIS CHAPTER. “ecstasy”). economic. Describe interventions to prevent or manage withdrawal reactions associated with barbiturates. Most are also associated with tolerance if used repeatedly. an 8th grader approaches you saying he is very worried about his friend. and compulsive self-administration. amphetamines. and other mind-altering drugs (eg. substance abuse is defined as selfadministration of a drug for prolonged periods or in excessive amounts to the point of producing physical or psychological dependence and reduced ability to function as a productive member of society. Outline major elements of treatment for overdoses of commonly abused drugs that do not have antidotes. child and spouse abuse. on a dare. CNS stimulants (eg. impaired family relationships). and continuing to take a drug despite adverse consequences (eg. drug-related illnesses. Psychological dependence involves feelings of satisfaction and pleasure from taking the drug. benzodiazepines. Substance abuse is often associated with substantial damage to the abuser and society (eg. marijuana. job loss or decreased ability to function in an occupation. and nicotine on selected body organs. mental or legal problems. death). nicotine). opioid analgesics). Most drugs of abuse are those that affect the CNS and alter the state of consciousness. social. Identify risk factors for development of drug dependence. Commonly abused drugs include CNS depressants (eg. cocaine and other CNS stimulants. crime. they are associated with feelings of pleasure. Just after lunch. especially during the adolescent period. and opiates. After lunch. Although these drugs produce 236 A different effects. positive reinforcement. 2. and opiates. ᮣ Discuss important follow-up with this adolescent and his family after the incident. Describe the effects of alcohol. that increase the likelihood a person will experiment with or abuse alcohol. 3. 4.

• Alcohol and other drug abusers are not reliable sources of information about the types or amounts of drugs used. Then. They include alcohol. and substitutions of one drug for another. 8). route of administration. family. Most abusers understate the amount and frequency of substance use. acute intoxication. death. 16). hepatitis. Health care professionals (eg. endocarditis. and other dangerous practices. Most of these have clinical usefulness and are discussed elsewhere: Antianxiety and Sedative-Hypnotic Drugs (see Chap. at least partly because of easy access. for example. opioids. In addition. withdrawal symptoms of alco- hol and sedative-type drugs are mainly agitation. and opiates. Thus. the amount. CENTRAL NERVOUS SYSTEM DEPRESSANTS CNS depressants are drugs that slow down or “depress” brain activity. poor hygiene. Withdrawal symptoms are characteristic for particular types of drugs and are usually opposite the effects originally produced. human immunodeficiency virus infection. they rapidly circulate to the heart and brain without dilution by the systemic circulation or metabolism by enzymes.CHAPTER 15 SUBSTANCE ABUSE DISORDERS 237 ceived as extremely desirable by the drug-dependent person. Additional general characteristics of substance abuse and dependence include the following: • Substance abuse involves all socioeconomic levels and almost all age groups. antianxiety and sedativehypnotic agents. frequency. those who use illegal street drugs may not know what they have taken because of varying purity. and its use is accepted in most societies. and route of administration are also important. and Central Nervous System Stimulants (see Chap. characteristics and treatment of substance-related disorders. organ damage. nurses) are also considered at high risk for development of substance abuse disorders. This chapter describes commonly abused substances. Tolerance is often an element of drug dependence. or serious medical problems resulting from chronic drug overuse. It is legal and readily available. • Substance abusers rarely seek health care unless circumstances force the issue. Specific problems include overdoses. and increasing doses are therefore required to obtain psychological effects or avoid physical withdrawal symptoms. alcohol. or abuse. from school-aged children to elderly adults. Alcohol (Ethanol) Alcohol is the most abused drug in the world. Attempts to avoid withdrawal symptoms reinforce psychological dependence and promote continuing drug use and relapses to drugtaking behavior. but . potency. and drugs used to treat substance-related disorders (see Drugs at a Glance: Drugs Used to Treat Substance Abuse Disorders). even if reared away from the abusing parent. misuse. heroin addicts may overstate the amount used in attempts to obtain higher doses of methadone. and return to drug-taking behavior after periods of abstinence. inhaling vapors from the heated drug produces blood levels comparable to those obtained with intravenous (IV) administration. acute intoxication often produces profound behavioral changes and chronic abuse often leads to serious organ damage and impaired ability to function in work. 6). pharmacists. Many drugs are abused for their mind-altering properties. and nicotine because the drugs are rapidly absorbed from the large surface area of the lungs. • A person who abuses one drug is likely to abuse others. One view is that drugs stimulate or inhibit neurotransmitters in the brain to produce pleasure and euphoria or to decrease unpleasant feelings such as anxiety. and medical illness). and sedatives are often used to combat the anxiety and nervousness induced by cocaine and other CNS stimulants. Thus. A genetic factor seems evident in alcohol abuse: Studies indicate that children of abusers are at risk of becoming abusers themselves. With crack cocaine. • Smoking or inhaling drug vapors is a preferred route of administration for cocaine. additives. marijuana. Patterns of abuse may vary in age groups. adolescents and young adults may be more likely to use illicit drugs and older adults are more likely to abuse alcohol and prescription drugs. Alcohol. duration of use. contaminated needles. The withdrawal or abstinence syndrome produces specific manifestations according to the type of drug and does not occur as long as adequate dosage is maintained. is often used with other drugs of abuse. Opioid Analgesics and Opioid Antagonists (see Chap. There is no clear dividing line between use and abuse. Peer pressure is often an important factor in initial and continuing drug ingestion. and cellulitis at injection sites). development and maintenance of drug abuse patterns. In addition. marijuana. contribute to acute intoxication. probably because it is legal and readily available. names. and hyperactivity. • Substance abusers who inject drugs intravenously are prey to serious problems because they use impure drugs of unknown potency. and phase of substance abuse (eg. nervousness. physicians. • Multiple drugs are often abused concurrently. and numerous infections (eg. For example. or social settings. In addition to drug effects. phlebitis. The specific drug and the amount. • Drug effects vary according to the type of substance being abused. most substance abuse comes to the attention of health care professionals when the abuser experiences a complication such as acute intoxication. For example. withdrawal syndromes. withdrawal. Physical dependence involves physiologic adaptation to chronic use of a drug so that unpleasant symptoms occur when the drug is stopped or its action is antagonized by another drug. Drug dependence is a complex phenomenon of unknown cause. A person may be dependent on more than one drug. other influencing factors include a person’s psychological and physiologic characteristics and environmental or circumstantial characteristics.

then increase to 150 mg twice daily. every 1–2 h. 2 wk needed for long-acting benzodiazepines Nicotine (Habitrol. PO 20–80 mg daily initially. alcohol withdrawal Opiate withdrawal. and phencyclidine. to a maximum of 80 sprays (40 mg) per day for heavy smokers. alcohol dependence Aid smoking cessation by relieving nicotine withdrawal symptoms Agitation. hallucinogens. 1 spray to each nostril. then discontinue Nicotrol nasal spray.3–0. others) Opiate dependence. 14 mg/d for 2 wk. 1 piece every 2–4 h for wks 7–9. opiate withdrawal Unlabeled uses May cause hypotension Disulfiram (Antabuse) Chronic alcohol abuse. benzodiazepine withdrawal Alcohol withdrawal. Maximum dose. Nicorette. alcohol withdrawal hallucinations or seizures. to prevent continued alcohol ingestion Flumazenil (Romazicon) Haloperidol (Haldol) Levomethadyl (LAAM) (Orlaam) Lorazepam (Ativan) Acute intoxication or overdose of benzodiazepine antianxiety or sedative-hypnotic drugs Psychotic symptoms associated with acute intoxication with cocaine and other central nervous system (CNS) stimulants Maintenance therapy of heroin addiction Excessive CNS stimulation associated with acute intoxication with cocaine and other CNS stimulants. marijuana. PO 2 mg q6–8h initially. Nicoderm: 21 mg/d for 6 wk. Habitrol. Nicotrol Inhaler. Nicoderm CQ. inhalants. then tapered over 1–2 wk Alcohol withdrawal PO 0. Nicotrol NS) Transdermal patches. 1 piece every 4–8 h for wks 10–12 Nicotrol inhaler. 300 mg/d PO 50 mg q6–8h initially.2 mg/min up to 1 mg Limited effectiveness because many alcoholics will not take the drug. 6–12 cartridges/d for 3 mo. repeated if necessary. should not be given until at least 12 h after alcohol ingestion May precipitate acute withdrawal symptoms Other antipsychotic agents may also be used IM 2–5 mg every 30 min to 6 h PRN for psychotic behavior PO 60–100 mg 3 times weekly Methadone Naloxone (Narcan) Naltrexone (ReVia) Acute intoxication or overdose of opiates (heroin. IM 2 mg. at least 8 hours apart. maintenance PO 20–80 mg daily IV 0. then gradually taper dosage over 6–12 wk.238 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Drugs at a Glance: Drugs Used to Treat Substance Abuse Disorders Generic/Trade Name Bupropion (Zyban) Indications for Use Smoking cessation Routes and Dosage Ranges PO 150 mg once daily for 3 days. they should be discarded in a safe manner .4–2 mg q3min PO 50 mg daily Reportedly as effective and well accepted by heroin addicts as methadone 1 wk of tapering usually adequate for withdrawal from short-acting benzodiazepines. maintenance therapy of heroin addiction IV 0. benzodiazepine withdrawal. Maintenance doses of 60–80 mg daily more effective than 20–30 mg daily in decreasing heroin use May precipitate acute withdrawal symptoms With opiate dependence. then tapered over 1–2 wk Withdrawal.6 mg q6h Opiate withdrawal PO 2 mcg/kg 3 times daily for 7–10 days PO 125–500 mg daily Comments Chlordiazepoxide (Librium) Clonidine (Catapres) Alcohol detoxification. IM q30 min–6 h PRN. morphine.1–0. should not be started until patient is opioid-free for at least 7 d Should not be used while continuing to smoke because of high risk of serious adverse effects Used patches contain enough nicotine to be toxic to children and pets. Nicotrol. 7 mg/d for 2 wk Nicotrol patch: 15 mg/16 hours for 6 wk Nicotrol chewing gum: 1 piece every 1–2 h for wks 1–6. reduced by 5–10 mg daily over 7–10 days. Taper by using less often or spraying 1 nostril per dose.

how rapidly it was ingested. such as thiamine. polyneuritis and Wernicke-Korsakoff syndrome. eventually produces severe liver injury characterized by necrosis and inflammation (alcoholic hepatitis) or by fibrous bands of scar tissue that irreversibly alter structure and function (cirrhosis). leading to accumulation and toxic effects. edema. which is most apparent in children born to alcoholic mothers. gynecomastia. chronic infection. thrombocytopenia and decreased platelet aggregation from folic acid deficiency. When alcohol is ingested orally. hypersplenism. and elevated creatine phosphokinase. a portion is inactivated in the stomach (by the enzyme alcohol dehydrogenase) and not absorbed systemically. and feminization in men with cirrhosis due to decreased secretion of male sex hormones. chronic myopathy. hypomagnesemia. insomnia. impaired motor coordination. alcohol is absorbed partly from the stomach but mostly from the upper small intestine. In men and women. pancreatic disease. decreases use and increases production of lipids. infection. damage to the epithelial cells of the intestinal mucosa. and conduction disturbances. The incidence of liver disease correlates with the amount of alcohol consumed and the progression of liver damage is attributed directly to ethanol or indirectly to the metabolic changes produced by ethanol. poor task performance. Women have less enzyme activity than men and therefore absorb approximately 30% more alcohol than men when comparable amounts are ingested according to weight and size. and vitamin B12. Hepatic Effects Induces drug-metabolizing enzymes that accelerate metabolism of alcohol and many other drugs and produces tolerance and cross-tolerance. Endocrine Effects Increased release of cortisol and catecholamines and decreased release of aldosterone from the adrenal glands. osteonecrosis due to obstructed blood supply. Alcohol is thought to exert its effects on the CNS by enhancing the activity of gamma-aminobutyric acid. and mental retardation becomes apparent. osteoporosis. abnormal T waves. sideroblastic anemia (sideroblasts are precursors of red blood cells) probably from nutritional deficiency. hypocalcemia. hypoglycemia due to impaired glucose synthesis or hyperglycemia due to glycogenolysis. iron deficiency anemia usually from gastrointestinal bleeding. nitrogen. and hypoactivity or hyperactivity. Muscular Effects Acute myopathy. possible impairment of coronary blood flow and myocardial contractility. decreased renal excretion of uric acid. The alcohol concentration in the brain rapidly approaches that in the blood. decreased numbers and impaired function of white blood cells. whereas others become evident with chronic intake of substantial amounts. mental depression. which may involve muscle weakness. These effects depend on the amount ingested. and other factors. Other effects include decreased bone density. tenderness. degenerative changes in the anterior pituitary gland. which may be manifested by acute pain. women are especially vulnerable to adverse effects of alcohol. Fetal alcohol syndrome is characterized by low birth weight and length and by birth defects. BOX 15–1 EFFECTS OF ALCOHOL ABUSE Hematologic Effects Bone marrow depression due to alcohol or associated conditions. decreased secretion of antidiuretic hormone from the posterior pituitary. Alcohol exerts profound metabolic and physiologic effects on all organ systems (Box 15–1). hypophosphatemia. impaired interpersonal relationships. cardiomyopathy manifested by cardiomegaly. and vitamin B12. an inhibitory neurotransmitter. and electrocardiographic changes indicating left ventricular hypertrophy.CHAPTER 15 SUBSTANCE ABUSE DISORDERS 239 rather a continuum of progression over several years. including protein and water-soluble vitamins. whether the stomach was empty. Cardiovascular Effects Damage to myocardial cells. and thinking processes. learning. brain damage. and secondary hyperuricemia. hemolytic anemia from abnormalities in the structure of red blood cells. with ataxia or staggering gait. decreases use and increases production of lactate. and increased susceptibility to fractures. Once absorbed. which lead to decreased resistance to infection. Food delays absorption by diluting the alcohol and delaying gastric emptying. such as cleft palate and cardiac septal defects. Some of these effects are evident with acute alcohol intake. Skeletal Effects Impaired growth and development. . leading to hyperlipidemia and fatty liver. increased intestinal motility. eventually damages the liver enough to impair drug metabolism. and fatty liver and bone marrow failure associated with cirrhosis. Impairment of growth and motor development persists in the postnatal period. folic acid. Fatty liver causes accumulation of fat and protein. or by inhibiting the activity of glutamate. impaired memory. Central and Peripheral Nervous System Effects Sedation ranging from drowsiness to coma. altered speech patterns. hypogonadism. including more rapid intoxication from smaller amounts of alcohol and earlier development of hepatic cirrhosis and other complications of alcohol abuse. anxiety. leading to hepatomegaly. which leads to bone resorption and decreased skeletal mass. alcohol is quickly distributed to all body tissues. several types of anemia including megaloblastic anemia from folic acid deficiency. abnormal heart sounds. It is rapidly absorbed when the stomach and small intestine are empty. which probably contributes to the diarrhea that often occurs with alcoholism. and anemias from hemodilution. partly because it is lipid soluble and crosses cell membranes easily. edema. and hyperkalemia. multiple nutritional deficiencies. and CNS effects usually occur within a few minutes. As a result. which contributes to malabsorption of fat. an excitatory neurotransmitter. which may further stimulate bone resorption. dyspnea. Gastrointestinal Effects Slowed gastric emptying time. and liver disease. episodes of acute myopathy associated with a drinking spree. probably from inadequate dietary intake of phosphorus. and other factors. leading to lactic acidosis. such as malnutrition. atrophy.

accidents. the second step is probably confronting the client with evidence of alcohol abuse and trying to elicit cooperation. and other signs of acute psychosis. to seek treatment for other disorders. • With oral anticoagulants (eg. if chronic ingestion has caused liver damage.240 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM Effects with acute intoxication usually progress from a feeling of relaxation to impaired mental and motor functions to stupor and sleep. The alcohol-dependent person is unlikely to seek treatment for alcohol abuse unless an acute situation forces the issue. it is difficult to predict effects of interactions in particular people. nausea and vomiting). This increases the risk of excessive anticoagulant effect and bleeding. cefotetan). such as nervousness. Effects are summarized in Box 15–1. causes liver damage and impaired ability to metabolize drugs. • With antihypertensive agents. and tricyclic antidepressants). postural hypotension. bronchospasm. Acute ingestion increases anticoagulant effects and the risk of bleeding. opioid analgesics. He or she is likely. a greater proportion of fatty tissue). and assaultiveness often result. 3 to 4 oz of wine. and to the extent that physical health and social relationships are impaired. disorientation. Acute ingestion inhibits drug-metabolizing enzymes. In older adults. aggressiveness. However. including several cephalosporin antibiotics (cefamandole. if severe. anxiety. Alcohol Dependence Alcohol dependence involves acute or chronic consumption of alcohol in excess of the limits accepted by the person’s culture. Signs and symptoms of alcohol withdrawal include agitation. antidiabetic agents. Although the rate of metabolism differs with acute ingestion or chronic intake and some other factors. Because so many variables influence alcohol’s interactions with other drugs. tolerance. warfarin). alcohol interactions vary. cefoperazone. or 8 to 12 oz of beer. Treatment of Alcohol Dependence Alcohol dependence is a progressive illness. This reaction may be used to treat alcohol dependence. Acute intoxication impairs thinking. and other effects. however. and outgoing or more impulsive and aggressive because inhibitions have been lessened. is characterized by confusion. hyperreflexia. tachycardia. These interactions often differ between acute and chronic ingestion. and gastroenteritis. chlorpropamide (Diabinese). Unless . tachycardia. sweating. and disturbed relationships with other people. However. This slows the metabolism of some drugs. the pharmacokinetics of alcohol are essentially the same as for younger adults. sedative-hypnotics. The rate of alcohol metabolism largely determines the duration of CNS effects. general anesthetics. This is the amount of alcohol contained in approximately 2/3 oz of whiskey. cefonicid. judgment. Chronic ingestion induces metabolizing enzymes. alcohol potentiates vasodilation and hypotensive effects. • With oral antidiabetic drugs. impaired mental and physical functioning. • A disulfiram-like reaction also may occur with other drugs. health professionals may recognize alcohol abuse in its early stages if they are aware of indicative assessment data. Chronic ingestion affects essentially all body systems and may cause severe organ damage and mental problems. anxiety. tremors. insomnia. however. Most alcohol is oxidized in the liver to acetaldehyde. the most serious form of alcohol withdrawal. • With disulfiram (Antabuse). The intensity of the alcohol withdrawal syndrome varies with the duration and amount of alcohol ingestion. nausea. Combining alcohol with these drugs may be lethal and should be avoided. Alcohol is metabolized at the same rate regardless of the amount present in body tissues. respiratory depression. However. Chronic ingestion decreases anticoagulant effects by inducing drugmetabolizing enzymes in the liver and increasing the rate of warfarin metabolism. oral anticoagulants. alcohol potentiates CNS depression and increases risks of excessive sedation. Psychological dependence. thereby increasing their effects and the likelihood of toxicity. antianxiety agents. and exhibitionism. When metabolized to acetaldehyde. If the first step of treatment is recognition of alcohol abuse. which normally controls behavior. Long-term ingestion of large amounts of alcohol. at times considered inappropriate by that culture. depression. talkative. ceforanide. The person may seem more relaxed. some important interactions include those with other CNS depressants. and psychomotor coordination. antipsychotic agents. alcohol produces significant distress (flushing. delusions. and cross-tolerance (with other CNS depressants) are prominent characteristics. and disulfiram. antihypertensive agents. tolbutamide (Orinase). alcohol potentiates hypoglycemic effects. alcohol no longer exerts depressant effects on the CNS. fever. physical dependence. Thus. and early recognition and treatment are desirable. sweating. and metronidazole (Flagyl). metabolism of warfarin may be slowed. it is approximately 120 mg/kg of body weight or 10 mL/hour. Excited behavior may occur because of depression of the cerebral cortex. These impairments lead to poor work performance. convulsions and delirium. This increases the rate of metabolism and decreases drug effects. These are summarized as follows: • With other CNS depressants (eg. Alcohol Interactions With Other Drugs Alcohol may cause several potentially significant interactions when used with other drugs. and. Withdrawal symptoms start within a few hours after a person’s last drink and last for several days. Delirium tremens. visual hallucinations. equivalent amounts of alcohol produce higher blood levels in older adults because of changes in body composition (eg. which can be used for energy or converted to fat and stored. Conscious control of behavior is lost.

syncope. Naltrexone is an opiate antagonist that reduces craving for alcohol and increases abstinence rates when combined with psychosocial treatment. and cross-tolerance. cooperation. tremors) associated with excessive stimulation of the sympathetic nervous system. cardiovascular collapse. and peak at 24 to 72 hours. lorazepam or oxazepam). Antiseizure drugs need not be given for more than a few days unless the person has a preexisting seizure disorder. success is unlikely. If the client is already sedated and stuporous. Combining any of these drugs with each other or with alcohol can cause serious depression of vital functions and death. Ingestion of prescription and over-the-counter medications that contain alcohol may cause a reaction in the disulfiram-treated alcoholic. as long as alcohol is present in the blood. Symptoms begin 12 to 24 hours after the last dose of a short-acting drug such as alprazolam (Xanax). and death. Midazolam or propofol may be useful for treating delirium tremens because their doses can be easily titrated to manage the symptoms. coma. Overdoses may cause respiratory depression. Disulfiram interferes with hepatic metabolism of alcohol and allows accumulation of acetaldehyde. memory impairment. The client must be closely observed because sedatives potentiate alcohol. a sedativetype drug may be given. The duration of the reaction varies from a few minutes to several hours. mainly because of poor compliance. headache. With phenobarbital. Disulfiram also interferes with the metabolism of phenytoin and warfarin. withdrawal symptoms begin 12 to 24 hours after the last dose and peak at 24 to 72 hours. such as depression. If the client is comatose. psychological dependence. alcohol abusers often need treatment of coexisting psychiatric disorders. Drug therapy for maintenance of sobriety is limited. Acute intoxication with alcohol does not usually require treatment. and excessive CNS depression may occur. even in overdose. blurred vision. hyperactivity. dizziness. Some physicians prefer a benzodiazepine with a long halflife (eg. which is thought to reinforce alcohol craving and consumption. A possible mechanism is blockade of the endogenous opioid system. after which they usually subside. Disulfiram alone may produce adverse reactions of drowsiness. They can help the client participate in rehabilitation programs and can be gradually reduced in dosage and discontinued. insomnia. drowsiness. myocardial infarction. Benzodiazepines are widely used for antianxiety and sedative-hypnotic effects (see Chap. and confusion. If the client agrees to treatment. others include anxiety. tremors and muscle twitch- . and confusion. and dermatitis. tachycardia. congestive heart failure. Withdrawal reactions can be extremely uncomfortable. Barbiturate and Benzodiazepine Dependence This type of dependence resembles alcohol dependence in symptoms of intoxication and withdrawal. For example. The client may fail to make return visits or may seek treatment elsewhere. With long-acting drugs such as diazepam (Valium) and chlordiazepoxide (Librium). Other characteristics include physical dependence. They provide adequate sedation and have a significant anticonvulsant effect. unless taken with alcohol or other drugs. mainly by people who also abuse alcohol or other drugs. Clonidine may be given to reduce symptoms (eg. With short-acting barbiturates such as pentobarbital (Nembutal) and secobarbital (Seconal). convulsions. In addition to drug therapy to treat withdrawal and maintain sobriety. tolerance. Lorazepam and oxazepam are less likely to accumulate and may be best for older adults or patients with hepatic disease. Seizures and death can occur. Naltrexone is hepatotoxic in high doses and contraindicated in patients with acute hepatitis or liver failure. and vomiting. symptoms begin 24 to 48 hours after the last dose and peak in 5 to 8 days. abusers often combine drugs in their quest for a greater “high” or to relieve the unpleasant effects of CNS stimulants and other street drugs. Seizures require treatment if they are repeated or continuous. and drug therapy. Benzodiazepine antianxiety agents are the drugs of choice for treating alcohol withdrawal syndromes. disulfiram must be given only with the client’s full consent. Severe reactions include respiratory depression. which may increase blood levels of the drugs and increase their toxicity. The severity of reactions varies but is usually proportional to the amounts of alcohol and disulfiram taken. poor motor coordination. he or she can be allowed to sleep off the alcohol effects. unconsciousness. Antidepressant drugs seem to decrease alcohol intake as well as relieve depression. symptoms begin 24 to 48 hours after the last dose and peak within 5 to 8 days. Signs and symptoms of withdrawal include anxiety. cause oversedation. The two drugs approved for this purpose are disulfiram (Antabuse) and naltrexone (ReVia). hypotension. impotence. nervousness. and knowledge. and death. headache. dyspnea. If the client is hyperactive and combative. diazepam or chlordiazepoxide) whereas others prefer one with a short half-life (eg. however.CHAPTER 15 SUBSTANCE ABUSE DISORDERS 241 the client admits that alcohol abuse is a problem and agrees to participate in a treatment program. The most common adverse effect is nausea. supportive measures are indicated. referral to a self-help group such as Alcoholics Anonymous. headache. respiratory depression may require insertion of an artificial airway and mechanical ventilation. cardiac arrhythmias. Because of these reactions. fatigue. acetaldehyde causes nausea and vomiting. Withdrawal is similar to alcohol withdrawal and may be more severe. Alcoholic patients usually require high doses of benzodiazepines because of the drugs’ cross-tolerance with alcohol. If alcohol is ingested during disulfiram therapy. They may. 8) and are also widely abused. the three primary approaches are psychological counseling. Barbiturates and Benzodiazepines Barbiturates are old drugs that are rarely used therapeutically but remain drugs of abuse. Benzodiazepines rarely cause respiratory depression or death. Unfortunately. These are more likely to occur during the first 2 weeks of treatment.

or nasal application (snorting). depending on the dose. insomnia. Opiate Dependence Opiates produce tolerance and high degrees of psychological and physical dependence. Convulsions are more likely to occur during the first 48 hours of withdrawal and delirium after 48 to 72 hours. and respiratory depression. Most other drugs that produce dependence do so with prolonged usage of large doses. These can be prevented by gradually withdrawing the offending drug. confusion. sedation. pupil constriction. There may be a period of excitement and emotional lability followed by progressively increasing signs of CNS depression (eg. and repeated IV injections are usually needed. postural hypotension. hypoglycemia. and delirium that resembles the delirium tremens of alcoholism or a major psychotic episode. nausea and vomiting. muscular incoordination. Treatment of withdrawal may involve administration of a benzodiazepine or phenobarbital to relieve acute signs and symptoms. Medical usage of these drugs produces physical dependence and tolerance but rarely leads to use or abuse for mind-altering effects. These treatments were formerly used for benzodiazepine overdoses and may still be needed in some cases (eg. If they do occur. Tolerance to euphoric effects develops rapidly. smoking. If there is no response to the opioid antagonist. a semisynthetic derivative of morphine. Effects diminish over approximately 4 hours. In addition to profound respiratory depression. The rate of recovery depends primarily on the amount of drug ingested and its rate of metabolism. and acute psychotic episodes. Treatment of Opiate Dependence Treatment may be needed for overdose or withdrawal syndromes. respiratory depression. tachycardia. dizziness. and physical and mental characteristics of the user. Insertion of an artificial airway and mechanical ventilation often are necessary. More severe overdoses cause respiratory depression and coma. Flumazenil (Romazicon) competes with benzodiazepines for benzodiazepine receptors. Heroin may be taken by IV injection. Gastric lavage may help if started within approximately 3 hours of drug ingestion. and is followed by a period of sedation. such as health care professionals or staff at detoxification centers. and sedation). Diuresis helps to eliminate the drugs and can be induced by IV fluids or diuretic drugs. which occurs within seconds. The client usually sleeps off the effects of the drug. weight loss. overdoses involving multiple drugs). postural hypotension. Hemodialysis also removes most of these drugs and may be used with high serum drug levels or failure to respond to other treatment measures. Treatment is unnecessary for mild overdose if vital functions are adequate. but morphine-like drugs produce dependence with repeated administration of small doses. pulmonary edema. 6). Signs and symptoms of withdrawal are less severe with the benzodiazepines than with the barbiturates.242 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM ing. Like other opiates. Withdrawal reactions should be supervised and managed by experienced people. The person may experience cardiovascular collapse. They are also commonly abused. Because therapeutic opiates are discussed elsewhere. Overdose may produce severe respiratory depression and coma. lasts a few minutes. the focus here is heroin. The drug has a short duration of action. a cuffed endotracheal tube should be inserted and the cuff inflated before lavage to prevent aspiration. It is a Schedule I drug in the United States and is not used therapeutically. Opiates Opiates are potent analgesics and extensively used in pain management (see Chap. distorted visual perceptions. coma. Insertion of an endotracheal tube and mechanical ventilation may be required. cycling between desired effects and symptoms of withdrawal. agitation. Acute effects of opiate administration vary according to dosage. Drug therapy consists of an opioid antagonist to reverse opioid effects. and constipation. generalized tonic-clonic seizures. Heroin. However. The goals of treatment are to maintain vital functions until the drug is metabolized and eliminated from the body. generalized tonic-clonic seizures. If the person is comatose. Overdose produces intoxication similar to that produced by alcohol. is a common drug of abuse. analgesia. Giving an opioid antagonist can precipitate withdrawal symptoms. Barbiturate and benzodiazepine withdrawal syndromes can be life threatening. and other infections often accompany opiate overdose and require specific treatment measures. the symptoms may be caused by depressant drugs other than opiates. weakness. There is no antidote for barbiturate overdose. a specific antidote is now available to reverse sedation. treatment is symptomatic and supportive. route of administration. then tapering the dose until the drug can be discontinued. leading to dosage escalation and continued use to avoid withdrawal. Recipients must be closely observed because symptoms of overdose may recur when the effects of a dose of flumazenil subside and because the drug may precipitate acute withdrawal symptoms (eg. “addiction” should not be an issue when the drugs are needed for pain management in patients with cancer or other severe illnesses. heroin causes severe respiratory depression with overdose and produces a characteristic abstinence syndrome. pneumonia. Hypotension and shock are usually treated with IV fluids. seizures) in benzodiazepine abusers. Thus. impaired mental function. IV injection produces intense euphoria. nightmares. each situation requires specific drug therapy and supportive measures. Addicts may inject several times daily. cellulitis. . vasodilation. They may produce euphoria. Treatment of Barbiturate or Benzodiazepine Abuse Treatment may involve overdose and withdrawal syndromes.

the goal of treatment for opiate abuse is abstinence from further opiate usage. acetaminophen or a nonsteroidal anti-inflammatory drug) should be given. these drugs may be part of a pattern of polydrug use in which CNS depressants. serotonin). because depression and sleep usually follow amphetamine use. The client is likely to be hyperactive. usually a single. however. also called LAAM. if given on a Monday/Wednesday/Friday schedule. wakefulness. withdrawal allows these conditions to emerge in an exaggerated form. long-term drug therapy may be used to treat heroin dependence. however. an antihypertensive drug. In addition. and recovering from a drug. CENTRAL NERVOUS SYSTEM STIMULANTS Amphetamines and Related Drugs Amphetamines and related drugs (see Chap. the drugs are more important as drugs of abuse than therapeutic agents. In addition. Also. Proponents say that methadone blocks euphoria produced by heroin. can be managed by gradually reducing dosage over several days. Cocaine Cocaine is a popular drug of abuse. Large amounts may cause psychosis (eg. using. opiates. It produces powerful CNS stimulation by preventing reuptake of neurotransmitters (eg. LAAM (Orlaam) is a synthetic. Because this goal is rarely met. Patients must be informed about the delayed effects of the drug and the risks of overdosage if they take other opiates. nonopioid analgesics (eg. which is more comfortable and safer. is sometimes used to relieve withdrawal symptoms associated with sympathetic nervous system overactivity. 16) are used therapeutically for narcolepsy and attention deficit-hyperactivity disorder (ADHD). LAAM has proarrhythmic effects and an electrocardiogram should be done prior to starting the drug and periodically during therapy. Sedative-type drugs must be used with great caution. the heroin addict does not commit crimes to obtain drugs. such as alcohol or sedative-type drugs (“downers”). Another drug approved for maintenance therapy is levomethadyl acetate hydrochloride. because methadone is free. it is recommended for use in conjunction with psychological counseling to promote client motivation and compliance. and hallucinating (toxic psychosis) and may have tachycardia. Treatment of Amphetamine-Type Abuse Treatment of amphetamine-type abuse is mainly concerned with overdosage because these drugs do not produce physical dependence and withdrawal as alcohol. it should be given in a setting staffed and equipped for cardiopulmonary resuscitation because respiratory depression may be deeper and more prolonged than usual. Except for the use of methylphenidate in treating ADHD.CHAPTER 15 SUBSTANCE ABUSE DISORDERS 243 Signs and symptoms of withdrawal can be reversed immediately by giving the drug producing the dependence. initial dosage needs careful titration to prevent withdrawal symptoms but avoid overdosage when peak effects occur. Methadone has long been used for this purpose. and other symptoms. which are then heated and the vapors smoked or inhaled. agitated. potent metabolites. Users may take them alone or to counteract the effects of other drugs. acts longer. Acute ingestion of these drugs masks underlying fatigue or depression. which increases . Its main advantage over methadone is that it can be given three times weekly rather than daily. Also. and administration of an antipsychotic drug. norepinephrine. the Friday dose may need to be larger to prevent withdrawal symptoms until the Monday dose can be given. Small amounts produce mental alertness. and reduces preoccupation with drug use. Because amphetamines delay gastric emptying. an opioid antagonist that prevents opiates from occupying receptor sites and thereby prevents their physiologic effects. and increased energy. fever. Amphetamine-Type Dependence Amphetamines and related drugs (eg. methamphetamine. and last about 72 hours. patients needing elective surgery and opioid analgesics should be instructed to stop taking naltrexone at least 72 hours before the scheduled procedure. peak in about 4 hours. After oral administration. a substantial percentage of those receiving methadone maintenance therapy abuse other drugs. Symptomatic treatment includes sedation. daily. including cocaine. and sedativehypnotic drugs do. In the latter case. If the patient taking naltrexone has mild or moderate pain. oral dose given in a methadone clinic. Ideally. Used to maintain opiate-free states in the opiate addict. One of the drugs. A third treatment option is naltrexone (ReVia). Schedule II opioid indicated only for the treatment of opiate dependence. This allows a more normal lifestyle for the client and reduces morbidity and mortality associated with the use of illegal and injected drugs. Clonidine. Psychological effects of amphetamines are similar to those produced by cocaine and are largely dose related. Therapeutic withdrawal. Opponents say that methadone maintenance only substitutes one type of drug dependence for another. effects occur within 90 minutes. methylphenidate) produce stimulation and euphoria. effects often sought by drug users. If the patient has severe pain and requires an opioid. lowering of body temperature. are alternated with CNS stimulants. Tolerance develops to amphetamines. The resulting exhaustion and depression reinforce the compulsion to continue using the drugs. such as amphetamines (“uppers”). However. dopamine. gastric lavage may be helpful even if several hours have passed since drug ingestion. may be chemically treated to produce potent crystals (called “ice”). It is metabolized to longacting. hallucinations and paranoid delusions). and these after-effects can be aggravated by sedative administration. The user may increase the amount and frequency of administration to reach or continue the state of stimulation. One method uses opioid substitutes to prevent withdrawal symptoms and improve a lifestyle that revolves around obtaining.

Poisoning may also occur with accidental ingestion of insecticide sprays containing nicotine. rupture of the aorta. cardiopathy. and drowsiness as drug effects wear off. and damage (ulceration. possible necrosis. It is prepared by altering cocaine hydrochloride with chemicals and heat to form rock-like formations of cocaine base. constriction of coronary and peripheral arteries. rhinitis. and its metabolites are eliminated by the kidneys. cellulitis. The average cigarette contains approximately 6 to 8 mg of nicotine and delivers approximately 1 mg of nicotine systemically to the smoker (most is burned or dissipated as “sidestream” smoke). convulsions. cancer and pulmonary BOX 15–2 PHYSIOLOGIC AND BEHAVIORAL EFFECTS OF COCAINE ABUSE striction and ischemia. It reportedly can cause psychological dependence with one use. excessive central nervous system stimulation. rhinorrhea. intestinal ischemia. agitation and hyperactivity may be treated with a benzodiazepine antianxiety agent. Crack is a strong. cardiac dysrhythmias may be treated with usual antidysrhythmic drugs. With inhalation of crack cocaine vapors. healthy adults and even with initial exposure. respiratory failure. psychosis may be treated with haloperidol or other antipsychotic agent. myocardial infarction may be treated by standard methods. However. dysphoria. ventricular tachycardia and fibrillation. delirium. manifested by anxiety. dyspnea. and fatal lung hemorrhage. Overdosage can cause cardiac dysrhythmias. hypertension. drowsiness. and dependence. Nicotine Nicotine. cough. Central Nervous System Effects Cerebral infarct. although fatigue. bronchospasm. skin. coma. and restlessness followed by depression. Effects of Intravenous Use Hepatitis. sexual arousal. respiratory arrest. myocardial infarction. mainly in the liver. weight loss. subarachnoid and other hemorrhages. including tachycardia. Nicotine obtained from chewing tobacco produces longer-lasting effects because it is more slowly absorbed than inhaled nicotine. Nicotine poisoning can occur in infants and children from ingestion of tobacco products. nicotine is implicated in the vascular disease and sudden cardiac death associated with smoking. human immunodeficiency virus infection. psychosis with paranoid delusions and hallucinations that may be indistinguishable from schizophrenia. insomnia. respiratory symptoms occur in up to 25% of users and may include bronchitis. perforation. “crack” is heated and the vapors inhaled. It is extensively metabolized. hyperactivity. irritability. stroke. fatigue. which limits the amount of nicotine absorbed. Both acute and chronic use produce numerous physiologic effects (Box 15–2). Long-term treatment of cocaine abuse usually involves psychotherapy. skin contact with used nicotine transdermal patches. stroke. Cocaine is not thought to produce physical dependence. pneumonia. depression. The process removes impurities and results in a very potent drug. cardiac dysrhythmias. Inhaling smoke from a cigarette produces CNS stimulation in a few seconds. or chewing nicotine gum. extremely addicting. Oral ingestion usually causes vomiting. Cocaine Dependence Cocaine-induced euphoria is intense but brief and often leads to drug ingestion every few minutes as long as the drug is available. pulmonary edema. In addition. Treatment of Cocaine Abuse Drug therapy is largely symptomatic. and mucous membranes. Toxic effects of a large dose may include hypertension. When the drug is heated and the vapors inhaled. Respiratory Effects With snorting of cocaine. and widely used form of cocaine. agitation. and so forth. With chronic tobacco use. Thus.244 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM and prolongs neurotransmitter effects. many patients need treatment for coexisting psychiatric disorders. and paralysis of skeletal muscle. and 12-step programs. inexpensive. seizures. and asystole. Gastrointestinal Effects Nausea. and death. Genitourinary Effects Delayed orgasm for men and women. difficulty in maintaining erection. increased energy and alertness. tachycardia. endocarditis. increased blood pressure. abuse. behavioral therapy. premature ventricular contractions. Cardiovascular Effects Dysrhythmias. Nicotine produces its effects by increasing levels of dopamine and other substances in the brain. abscesses. and intense craving occur as drug effects dissipate. myocardial ischemia and acute myocardial infarction. anorexia and weight loss. convulsions. crack acts within a few seconds. Acute use of cocaine or crack produces intense euphoria. Initial detoxification and long-term treatment are best accomplished in centers or units that specialize in substance abuse disorders. Cocaine is commonly inhaled (snorted) through the nose. necrosis) of the nasal septum from vasocon- . even in young. Adverse effects include nausea in new smokers at low blood levels and in experienced smokers at blood levels higher than their accustomed levels. the role of nicotine in the etiology of other disorders (eg. It is also excreted in breast milk of nursing mothers. one of many active ingredients in tobacco products. Nicotine is readily absorbed through the lungs. is the ingredient that promotes compulsive use.

dysrhythmias. These cannabis preparations contain several related compounds called cannabinoids. It is also difficult to predict the effects of these drugs.CHAPTER 15 SUBSTANCE ABUSE DISORDERS 245 disease) associated with chronic use of tobacco is unknown. vasoconstriction. chewing gum. The other method is nicotine replacement therapy with drug formulations of nicotine. convulsions at high doses. Marijuana is obtained from leaves and stems. Nicotine Dependence Like alcohol and opiate dependence. increased appetite. weight gain. The products are contraindicated in people with significant cardiovascular disease (angina pectoris. a combination of Zyban and nicotine transdermal patches is sometimes used and may be more effective than either drug alone. These products prevent or reduce withdrawal symptoms. The mechanism of action is unknown. there are two main methods of treatment. Adverse effects include soreness of mouth and throat (with gum). and the environment in which the drug is taken. some call them stimulants. increased blood pressure. psychotomimetic. nausea and vomiting. Effects are summarized in Box 15–3. The antidepressant formulation is marketed as Wellbutrin. and a nasal spray. and others label them as mind-altering. the transdermal patch is applied once daily. 10). Transdermal patches produce a steady blood level of nicotine and patients seem to use them more consistently than they use the other products. Central Nervous System Effects Central nervous system stimulation with increased alertness. anxiety. which usually begin within 24 hours of the last exposure to nicotine. which varies with the climate and soil where the plants are grown and with the method of preparation. which grows in most parts of the world. The endogenous substances that react with these receptors have not been determined. increased force of myocardial contraction. Nicotine is available in transdermal patches. the inhaler and nasal spray require a prescription. dysrhythmias. Delta-9-tetrahydrocannabinol (∆-9-THC) is the main psychoactive ingredient. Overall. and increased cardiac workload. headache. confusion. Cannabis preparations are difficult to classify. but they do not produce the subjective effects or peak blood levels seen with cigarettes. irritability. an antidepressant (see Chap. dizziness. hallucinogenic. treatment regimens that combine counseling and behavioral therapy with drug therapy are more successful than those using drug therapy alone. increases muscle tone and motility. and spray are used intermittently during the day. Abstinence from smoking leads to signs and symptoms of withdrawal (eg. The patches and gum are available over the counter. and skin irritation at sites of transdermal patch application. vomiting. Many factors apparently influence a person’s response. or unique in terms of fitting into drug categories. Other factors include dose. including the entire United States. nicotine dependence is characterized by compulsive use and the development of tolerance and physical dependence. In addition. One factor is the amount of active ingredients. nausea. For those who are strongly dependent and unable or unwilling to quit on their own. sleep disturbances). decreased appetite. It is more potent and more rapid in its actions when inhaled. an oral inhaler. difficulty concentrating. Mental depression is also associated with nicotine dependence. The gum. Treatment of Nicotine Dependence Most tobacco users who quit do so on their own. restlessness. subjective BOX 15–3 EFFECTS OF NICOTINE Gastrointestinal Effects Increases secretion of gastric acid. Evidence indicates a compulsion to smoke when blood levels of nicotine become low. Cigarette smokers may smoke to obtain the perceived pleasure of nicotine’s effects. although specific cannabinoid receptors have been identified in several regions of the brain. . or recent myocardial infarction). Marijuana Marijuana and other cannabis preparations are obtained from Cannabis sativa. hypertension. Marijuana can be taken orally but is more often smoked and inhaled through the lungs. with tapering of dosage and discontinuation. Cardiovascular Effects Cardiac stimulation with tachycardia. tremors. prepared from plant resin. One method is the use of bupropion. the hemp plant. inhaler. Nicotine products are intended to be used for limited periods of 3 to 6 months. or both. a sustained-release tablet. many resume smoking. possibly feelings of enjoyment. but metabolites and other constituents also may exert pharmacologic activity. personality variables. avoid the discomfort of nicotine withdrawal. After smoking. Although they are effective in helping smokers achieve abstinence. Some people call them depressants. the smoking-cessation formulation is Zyban. aggravates gastroesophageal and peptic ulcer disease. hashish. is 5 to 10 times as potent as commonly available marijuana. It is unknown whether depression leads to smoking or develops concomitantly with nicotine dependence. Marijuana and hashish are the two cannabis preparations used in the United States. route of administration.

hyperthermia. and body temperature. decreased libido. orthostatic hypotension and tachycardia at high doses. Central Nervous System Effects Impaired memory. Another major concern is the drug’s neurotoxicity. and the drug may cause physical and psychological dependence. heart rate. Marijuana Dependence Tolerance and psychological dependence do not usually develop with occasional use but may occur with chronic use. impairs most intellectual functions. and death. Cannabinoids can also decrease intraocular pressure and may be useful in treating glaucoma. MDMA floods the brain with high amounts of serotonin. perceptual. thirst. involuntary jaw clenching.246 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM effects begin in minutes. drowsiness with high doses. euphoria. weeks. increased reaction time. Users report increased energy and perception. hypertension. and lung cancer (some known carcinogens are much higher in marijuana smoke than in tobacco smoke). LSD alters sensory perceptions and thought processes. drug use is usually followed by several days of depression. and memory. is used to treat nausea and vomiting associated with anticancer drugs and to stimulate appetite in patients with acquired immunodeficiency syndrome (AIDS). and last 2 to 3 hours. However. low energy. a compound in ergot and some varieties of morning glory seeds. Effects wear off as THC is metabolized to inactive products. including increased blood pressure. Except for dronabinol (Marinol). tachycardia. It is usually taken by adolescents and young adults. Adverse effects include cardiac dysrhythmias. seizures. hallucinations. tablet. As a result. distorts perception of time and space. repeated use of MDMA may lead BOX 15–4 EFFECTS OF MARIJUANA people. Many physiologic effects (Box 15–4) and adverse reactions have been reported with marijuana use. clinicians state that such usage is no more effective than available legal treatments with less abuse potential. sadness. Respiratory Effects Irritation and cellular changes in bronchial mucosa. delusions. violent behavior. distorted sensory perceptions. and produces sympathomimetic reactions. paranoid ideation. marijuana and other cannabis preparations are illegal and not used therapeutically in most of the United States. and effects cannot be predicted accurately. mood alteration. mood. and possible chromosomal damage resulting in birth defects. depersonalization. which is important in emotion. Adverse reactions include self-injury and possibly suicide. often at dance parties called “raves. such as memory and problem-solving ability. Cardiovascular Effects Hypertension. disturbances in time perception. It is a Schedule III controlled drug. a formulation of ∆-9-THC. There is no specific treatment other than abstinence. These effects occur within an hour after oral ingestion and last 6 to 8 hours. Large doses can produce panic reactions and hallucinations similar to acute psychosis. or liquid form. coma. restlessness. peak in approximately 30 minutes. evidence indicates it is extremely dangerous. “flashbacks” (a phenomenon characterized by psychological effects and hallucinations that may recur days. pupil dilation. decreased intraocular pressure. or months after the drug is taken). Musculoskeletal Effects Ataxia. rhabdomyolysis. Although users apparently think this is a safe drug. Long-term or permanent changes may result from damage to the nerve cells in the brain that transmit serotonin. impaired performance on cognitive.” is an illegal. Schedule I derivative of amphetamine that produces hallucinogenic and stimulant effects when taken orally. hyponatremia. Low doses are mildly intoxicating and similar to small amounts of alcohol. panic reactions. The risks of abuse are high. possibly increased risk of mouth. These effects have occurred with a single use. impaired gas exchange. LSD is usually distributed as a soluble powder and ingested in capsule. bradycardia. The exact mechanism of action is unknown. throat. elevated body temperature. and psychomotor tasks. including impaired ability to drive an automobile and perform other common tasks of everyday life. and teeth grinding. and feelings of closeness to others. Early effects include spasmodic jerking. Even without these life-threatening adverse effects. peripheral vasoconstriction. and a decreased ability to feel emotions or pleasure. as well as pupil dilation. physical dependence rarely occurs. and small doses can alter normal brain functioning. LSD (lysergic acid diethylamide) is a synthetic derivative of lysergic acid. Some people promote legalization of marijuana for medical uses. aspergillosis in immunocompromised . bronchospasm. perceptual and sensory distortions. commonly called “ecstasy. dehydration. and elevated blood pressure. Miscellaneous Effects Constipation. psychotic episodes. delirium.4 methylenedioxymethamphetamine).” and its use is reportedly increasing. Dronabinol. depersonalization. Hallucinogens Hallucinogenic drugs include a variety of substances that cause mood changes. impaired coordination. anxiety. MDMA (3. It is very potent.

and loss of selfcontrol. the drug user may experience severe and unexpected reactions. such as antianxiety agents. delirium. Mescaline is an alkaloid of the peyote cactus. users also need to be concerned about the actual product they are taking. Emergency treatment of MDMA abuse usually involves decreasing the high body temperature. In addition to adverse effects of MDMA. Bizarre murders. and pressor effects that can cause hypertensive crisis. but they apparently do without or substitute another drug if the one they favor is unavailable. impaired thought processes. cocaine. and sniff the fumes. and sedative-hypnotics. or THC (the active ingredient in marijuana). insomnia. sedation and analgesia. Death from overdose also has occurred as a result of respiratory depression. and bone marrow. opioids. These substances produce symptoms comparable with those of acute alcohol intoxication. including abuse of prescription drugs. Consequently. and other profound psychological and physiologic effects. Collins is admitted for cirrhosis after an acute drinking episode. hallucinations. Nursing Process Assessment Assess clients for signs of alcohol and other drug abuse. and self-mutilations have been attributed to the schizophrenic reaction induced by PCP. “This is the third time she has been admitted for her drinking. Nursing Notes: Ethical/Legal Dilemma You are working on a medical unit when Mrs. All of these drugs may have serious adverse effects as well. Users may prefer one of these drugs. and other products. aerosol sprays. coma. A major danger with these drugs is their ability to impair judgment and insight. ketamine. It is usually sprayed or sprinkled on marijuana or herbs and smoked. inhaled. but there is no apparent physical dependence or abstinence syndrome. and death. Volatile solvents are most often abused by preadolescents and adolescents who squeeze glue into a plastic bag. Volatile Solvents (Inhalants) These drugs include acetone. There have been numerous reports of other drugs (eg. Some . and opiates. barbiturates. Some general screening-type questions are appropriate for any initial nursing assessment. Hallucinogen Dependence Tolerance develops. There is some question about whether physical dependence occurs. including a state of intoxication similar to that produced by alcohol. Phencyclidine (PCP) produces excitement. PCP is often sold as LSD.” Reflect on: • What are your feelings about caring for someone who abuses drugs or alcohol? • How would you feel if you heard the coworker speaking judgmentally? • Role play what you might say to the coworker. replacing fluids and electrolytes. Phencyclidine is usually distributed in liquid or crystal form and can be ingested. Suffocation sometimes occurs when the sniffer loses consciousness while the bag covers the face. altered sensory perceptions. Psychological dependence probably occurs but is usually not intense. These solvents may be constituents of some types of glue. Large doses may cause convulsions.CHAPTER 15 SUBSTANCE ABUSE DISORDERS 247 to depression. memory impairment. It is the least active of the commonly used psychotomimetic agents but produces effects similar to those of LSD. and disorientation. convulsions. kidneys. especially in high doses. confusion. and some produce tolerance. Substances containing gasoline. It is usually ingested in the form of a soluble powder or capsule. plastic cements. such as nitrous oxide. MDMA is not thought to cause dependence or withdrawal syndromes. psychotic reactions. or phencyclidine [PCP]) being sold as ecstasy. cerebral hemorrhage. suicides. It is also added to low-potency marijuana without the user’s knowledge. or carbon tetrachloride are especially likely to cause serious damage to the liver. LSD. toluene. Probably because it is cheap. mescaline. or injected. by running into traffic). Some substances in gasoline and toluene also may produce symptoms similar to those produced by the hallucinogens. You overhear a coworker stating. have also been abused to the point of dependence. for example. nystagmus and diplopia. hallucinations. If it does occur. These substances produce psychological dependence. including euphoria. and gasoline. easily synthesized. coma. Those who experience severe panic reactions may be kept in a safe. benzene. The overall purpose of these questions is to determine whether a current or potential problem exists and whether additional information is needed. and monitoring for cardiovascular complications. and it is the taxpayers that end up paying her bill. in a very judgmental tone. including death. and low energy or passivity. impaired motor skills. and death. The drug also produces flashbacks. recklessness. Some general inhalation anesthetics. It is very hard for me even to go in the room and take care of her. including initial mild euphoria followed by ataxia. it is considered less intense than the physical dependence associated with alcohol. and readily available. which can lead to panic reactions in which users may try to injure themselves (eg. supportive environment until drug effects wear off or may be given a sedative-type drug. methamphetamine. Treatment of Hallucinogen Abuse There is no specific treatment for hallucinogen dependence.

Inform smokers with young children in the home that cigarette smoke can precipitate or aggravate asthma and upper respiratory disorders in children. Useful information includes each specific drug. commits no injury to self or others). • Interview the client regarding alcohol and other drug use to help determine immediate and long-term nursing care needs. Inform smokers with nonsmoking spouses or other members of the household that “second-hand” smoke can increase the risks of cancer and lung disease in the nonsmokers as well as the smoker. hepatitis. such as long-term use of alcohol or psychotropic drugs. Observe for use or avoidance of nonprescribed drugs while hospitalized. For nurses who often encounter substance abusers. the frequency of administration. and psychiatric problems of anxiety or depression. and alcohol and drug levels in the blood. Teach nondrug techniques for coping with stress and anxiety. of course. If answers to general questions reveal problem areas. the amount. • Decrease environmental stimuli for the person undergoing drug withdrawal. and are nonspecific. hyperactivity or hypoactivity. • Record vital signs. and abuse of multiple drugs is a more common pattern than abuse of a single drug. efforts to keep up with drug names and terminology may be helpful. • Dysfunctional Family Processes: Alcoholism • Risk for Injury: Infection. health-related benefits of stopping substance use or abuse. frequently changed names. mental status. • Assess for disorders that may be caused by substance abuse. treatment programs). • Assess behavior that may indicate drug abuse. hypomagnesemia. and available services or treatment options. and behavior at regular intervals.248 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM clients may refuse to answer or give answers that contradict other assessment data. • Risk for Injury: Adverse effects of abused drug(s) • Disturbed Thought Processes related to use of psychoactive drugs • Risk for Other. and impulsive behavior • Imbalanced Nutrition: Less Than Body Requirements related to drug effects and drug-seeking behavior . and the duration of administration. respiratory. or self-help programs when indicated. and discuss ways to control weight without smoking. Use therapeutic communication skills to discuss alcohol or other drug-related health problems. Impairments in work performance and in interpersonal relationships also may be behavioral clues. altered speech patterns. • Information will be provided regarding drug effects and treatment resources. nurse clinical specialists. Interventions • Administer prescribed drugs correctly during acute intoxication or withdrawal. cardiovascular. • • • • • Nursing Diagnoses • Ineffective Coping related to reliance on alcohol or other drugs Evaluation • Observe for improved behavior (eg. abnormal white blood cell counts. • Check laboratory reports. • The client’s efforts toward stopping drug usage will be recognized and reinforced. Provide positive reinforcement for efforts toward quitting substance abuse. Observe for appropriate use of drugs to decrease abuse of other drugs. impaired judgment. and acidosis are common in alcoholics). Support use of resources for stopping drug abuse (psychotherapy. more specific questions can be formulated to assess the scope and depth of the problem. These and other factors aid effective planning of nursing care. information may be obtained that would indicate the likelihood of a withdrawal reaction. less impulsiveness. when available.” most of which have numerous. liver disease. These disorders may include infections. AIDS related to use of contaminated needles and syringes for IV drugs Planning/Goals • Safety will be maintained for clients impaired by alcohol and drug abuse.or Self-Directed Violence related to disturbed thought processes. and other signs of excessive central nervous system (CNS) depression or stimulation. Request patient referrals to psychiatric/mental health physicians. • • • • improved judgment and thought processes. such as alcohol on the breath. for abnormal liver function test results. emphasize that the health benefits of quitting far outweigh the disadvantages of gaining a few pounds. accidental injuries. Denial of excessive drinking and of problems resulting from alcohol use is a prominent characteristic of alcoholism. the risk of increased or decreased effects of a variety of drugs. For example. For smokers who are concerned about weight gain if they quit smoking. staggering gait. abnormal electrolytes (hypocalcemia. These disorders may be caused by other factors. and the client’s susceptibility to drug abuse. and neu• • • rologic functions. People who abuse one drug are likely to abuse others. underreporting the extent of drug use is common in other types of drug abuse as well. Interview to determine the client’s insight into personal problems stemming from drug abuse. It may be especially difficult to obtain needed information about illegal “street drugs. indications of anemia. Verify enrollment in a treatment program.

using nondrug measures when possible. laws designate certain drugs as illegal and provide penalties for possession or use of these drugs. PRINCIPLES OF THERAPY Prevention of Alcohol and Other Drug Abuse Use measures to prevent substance abuse. laws regulate the sale of alcoholic beverages. Since you are an RN. to take a drug or not to take it. however inappropriately. MD 20857 Phone: (301) 443-0365 E-Mail: nnadal@samhsa. Each person must take personal responsibility for drinking alcoholic beverages and taking mind-altering drugs. Of course. there are many appropriate uses of drugs. it is very difficult but more effective in the long run. what advice can you give her regarding smoking cessation? 3. using nondrug measures when they are likely to be effective. some of the following community-wide and individual measures may be helpful: 1. and if either parent is a heavy cigarette smoker. In some groups. Many current attitudes seem to promote drug use. This is especially prevalent in high school and college students. participating in drug education programs. For example. 4. b. Most efforts at prevention have tried to reduce the supply of drugs. Also. She went to her physician for a prescription for “the patch” and she even bought some nicotine gum at the drug store in case the cravings get really bad.CHAPTER 15 SUBSTANCE ABUSE DISORDERS 249 Nursing Notes: Apply Your Knowledge Your daughter brings her college roommate home for a weekend visit. educating clients about the drugs prescribed for them. Physicians can help prevent drug abuse by prescribing drugs appropriately.nih. You notice a patch on her right upper arm and her left upper arm. every social occasion is accompanied by alcoholic beverages of some kind.gov www.org Parents can help prevent drug abuse in their children by minimizing their own use of drugs and by avoiding heavy cigarette smoking. Treatment Measures for Substance Abuse Treatment measures for alcohol and other drug abuse are not very successful. prescribing mind-altering drugs in limited amounts and for limited periods. She tells you she has tried to quit smoking many times before but this time she is determined. Decrease the supply or availability of commonly abused drugs. but drug dependence develops in most instances only after prolonged use. The apparently prevalent view that drug abuse refers only to the use of illegal drugs and that using alcohol or prescription drugs. nicotine. Even people who have been institutionalized . MD 20892-9561 Phone: (301) 443-1124 www.nida. teaching clients about drugs prescribed for them.gov National Clearinghouse for Alcohol and Drug Abuse Information (NCADI) Center for Substance Abuse Prevention 5600 Fishers Lane Rockwall II Rockville. The widespread acceptance and use of alcohol. Other laws regulate circumstances in which legal drugs. conscious. and clients certainly should not be denied their benefits. as well as the mother of a friend. Although there are difficulties in trying to prevent conditions for which causes are not known. The belief that a drug is available for every mental and physical discomfort and should be taken in preference to tolerating even minor discomfort. Some resources for information and educational materials include the following: National Institute on Drug Abuse 6001 Executive Blvd Bethesda. Efforts to change attitudes and decrease demand for drugs can be made through education and counseling about such topics as drug effects and nondrug ways to handle the stresses and problems of daily life. and recognizing. may be used. Consequently. as early as possible. misuse. voluntary choices are made to drink or not to drink. society has a permissive attitude toward taking drugs. When mind-altering drugs are prescribed for a legitimate reason. and participating in drug education programs. including: a. and abuse. 7. 6. and this attitude is probably perpetuated by physicians who are quick to prescribe drugs and nurses who are quick to administer them.health. c. if either parent takes mind-altering drugs regularly. Children are more likely to use illegal drugs if their parents have a generally permissive attitude about drug taking. Nurses can help prevent drug abuse by administering drugs appropriately. The difficulties emerge when there is excessive reliance on drugs as chemical solutions to problems that are not amenable to chemical solutions. 5. Initially. and other drugs of abuse because of potentially harmful effects on the fetus. clients who are abusing or are likely to abuse drugs. 2. does not constitute drug abuse. Decrease the demand for drugs. This period varies somewhat. Pregnant women should avoid alcohol. such as opioid analgesics and barbiturates. The acceptance and use of illegal drugs in certain subgroups of the population. d. Because this involves changing attitudes. the client must use them in prescribed doses and preferably for a short time.

The neurologic complications and consequences of ethanol use and abuse. and other types of emotional support and counseling. Kelley’s Textbook of internal medicine. benzodiazepine antianxiety or hypnotic agents. D. 4. R. Philadelphia: Lippincott Williams & Wilkins. (2002). Alcoholism.. (2000). (2000). Philadelphia: Lippincott Williams & Wilkins. Pediatrics. 7th ed.. 4th ed. O’Brien. or various medical-surgical conditions. pp. Gourley (Eds. J. 65(3). Treatment of substance abuse may be complicated by the presence of other disorders. Louis: Facts and Comparisons. Despite these drawbacks. (Ed.. voluntary self-help groups. A. 2. L. For example. It is also important to tell her she must apply only one patch at a time and avoid concurrent use of nicotine gum to prevent nicotine toxicity. 284–289. S. pp. Herfindal & D. there is a high risk of substituting one abused drug for another. J. J. Kelley’s Textbook of internal medicine. including psychotherapy. there are few guidelines for optimal use. 7th ed. Textbook of therapeutics: Drug and disease management. American Family Physician. A. G. So far. Marijuana. and opiates? 3. Phipps. W. must often be estimated initially and then titrated according to response. B. Psychological rehabilitation efforts should be part of any treatment program for a drug-dependent person. In H. such as respiration and circulation. H. and duration of drug-taking behavior and the particular situation for which treatment is needed. C. Henderson-Martin. Substance abuse. still a crude drug with underappreciated toxicity. 351–358. DerMarderosian. Enoch. Cardiovascular complications of cocaine use.. A. or safely managed? 7. 229–233.. Marijuana: A decade and a half later. 4th ed. Review and Application Exercises 1. including treatment of overdose or withdrawal syndromes. N. A. General care of clients with drug overdose is primarily symptomatic and supportive. 3. Hashimoto.250 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM and achieved a drug-free state for prolonged periods are apt to resume their drug-taking behavior when released from the institution. First. pp. Jr. (2002). 345(5). there is often inadequate information about the types and amounts of drugs taken..). Drug therapy is limited in treating drug dependence for several reasons. What are the advantages of treating substance abuse disorders in centers established for that purpose? SELECTED REFERENCES Cooke. 441–450. . Herfindal & D.. American Journal of Nursing.. Removal of some drugs can be hastened by hemodialysis. 26–32. In E. 5. pp. however. cocaine. 2933–2936. & Tong. M. & Hillis. Gourley (Eds. R.) (2001). D. have been more successful than health professionals in dealing with drug abuse. Baldwin. extent. New England Journal of Medicine. Nursing Notes: Apply Your Knowledge Answer: Although you are not in a formal professional relationship with this young woman. (2000). R. and vice versa. pp. S. T. Second. Even when drug therapy is indicated. D. (2000). In E. Lobo. Tell her how proud you are that she is trying to quit and that research shows that it usually takes many attempts before success is obtained. treatment depends on the type. S. Humes (Ed. for example. depression is common and may require antidepressant drug therapy. there are significant drawbacks to giving CNS stimulants to reverse effects of CNS depressants. The aim of treatment is usually to support vital functions. specific antidotes are available only for benzodiazepines (flumazenil) and opioid narcotics (naloxone). it is important to support her efforts in smoking cessation. & Paty. Emergency: Delirium tremens. such as intoxication or overdose. III (2000). (2001). What are general interventions for treatment of drug overdoses? 4. 100(5). R. T. Philadelphia: Lippincott Williams & Wilkins. such as Alcoholics Anonymous and Narcotics Anonymous. 100(9). Philadelphia: Lippincott Williams & Wilkins. For example. Schwartz. Which commonly abused drugs may produce lifethreatening withdrawal reactions if stopped abruptly? 6. T.). D. What are specific antidotes for opiate and benzodiazepine overdoses. Problem drinking and alcoholism: Diagnosis and treatment. In H. As a general rule. Lange. Why is it important to assess each client in relation to alcohol and other substance abuse? 2. How can severe withdrawal syndromes be prevented. & Eoff. Health professionals are more likely to be involved in acute situations. Third. 1313–1341. 391–393.). What are signs and symptoms of overdose with alcohol. D. 41–42. C. D. C. 1289–1312. (2000). minimized. Approach to the problem of substance abuse. St. and how are they administered? 5. Sachse. respiratory depression from an overdose of a CNS depressant drug may be treated by inserting an artificial airway and me- chanical ventilation. there are some clinical indications for drug therapy. voluntary groups. P. In The review of natural products. L. until the drug is metabolized and eliminated from the body. Fourth. R. 109(2). American Journal of Nursing.. Humes (Ed. & Goldman. B. Textbook of therapeutics: Drug and disease management. Refer her back to her health care provider if she has additional questions or concerns.). Doses. Several approaches may be useful. No more surprises: Screening patients for alcohol abuse. Some general management principles include the following: 1. withdrawal syndromes.

restlessness. Reflect on: ᮣ What advice you would have for Mrs. and disturbances of nighttime sleep patterns. muscle weakness and hallucinations at onset of sleep. fatigue. Discuss reasons for decreased use of amphetamines for therapeutic purposes. who encouraged her to talk with a physician about prescribing Ritalin. recognize.chapter 16 Central Nervous System Stimulants Objectives AFTER STUDYING THIS CHAPTER. and short naps may be helpful in reducing daytime sleepiness. 2. because her son may have attention deficit-hyperactivity disorder (ADHD). THE STUDENT WILL BE ABLE TO: 1. although she would like to see his grades improve. Identify nursing interventions to prevent. It occurs before 7 years of age and is characterized by persistent hyperactivity. sleep studies are required for an accurate diagnosis. and their indications for use are limited. She was talking to a neighbor. Williams. M known. ᮣ Possible negative effects if the boy does not have ADHD. classrooms). but only a few are used therapeutically. 5. Signs and symptoms also include excessive daytime drowsiness. He seems to be doing OK in school. peer groups. avoiding shift work. Formerly thought to disappear with adolescence. family members. Identify effects and sources of caffeine. regular sleeping and waking times. and impulsiveness. Describe general characteristics of central nervous system (CNS) stimulant drugs. Attention Deficit-Hyperactivity Disorder ADHD is reportedly the most common psychiatric or neurobehavioral disorder in children. Narcolepsy affects men and women equally and usually starts during teenage or young adult years. prevention of sleep deprivation. Such behaviors make it difficult for the child to get along with others (eg. In adolescents and adults. Critical Thinking Scenario Mrs. and treat stimulant overdose. teachers) and to function in situations requiring more controlled behavior (eg. 4. impulsiveness and inattention continue but hyperactivity is 251 Narcolepsy Narcolepsy is a sleep disorder characterized by daytime “sleep attacks” in which the victim goes to sleep at any place or any time. Two disorders treated with CNS stimulants are narcolepsy and attention deficit-hyperactivity disorder (ADHD). orderly house and he likes to make messes. ᮣ Possible therapeutic effects if the boy has ADHD. Its cause is un- . USES any drugs stimulate the CNS. Williams comes to your office with her 6-year-old son. difficulty completing assigned tasks or schoolwork. She complains that he is a very active child who always seems to be getting into mischief. The hazards of drowsiness during normal waking hours and suddenly going to sleep in unsafe environments restrict activities of daily living. ADHD is now thought to continue into adolescence and adulthood in one third to two thirds of clients. a short attention span. 3. Discuss the rationale for treating attention deficit-hyperactivity disorder with CNS stimulant drugs. In addition to drug therapy. She likes a clean.

Overdoses can produce convulsions and psychotic behavior. Other effects include myocardial stimulation with increased cardiac output and heart rate. and confusion. Caffeine (a xanthine) is an ingredient in nonprescription analgesics and stimulants that promote wakefulness (eg. No-Doz). A major criterion for diagnosing later ADHD is a previous diagnosis of childhood ADHD. Analeptics Doxapram (Dopram) is occasionally used by anesthesiologists and pulmonary specialists as a respiratory stimulant. In children. dopamine. The major groups are amphetamines and related drugs. Large doses can impair mental and physical functions by producing restlessness. and xanthines. dysrhythmias. Most of a dose is metabolized in the liver and excreted in urine. Like other CNS stimulants. cardiac dysrhythmias. and increased secretion of pepsin and hydrochloric acid. It is well absorbed with oral administration. Analeptics are infrequently used (see doxapram and modafinil.5 hours. Contraindications to Use Central nervous system stimulants cause cardiac stimulation and thus are contraindicated in clients with cardiovascular disorders (eg. Modafinil (Provigil) is a newer drug for treatment of narcolepsy. hyperactivity. nervousness. diuresis. dextroamphetamine (Dexedrine). A combination of caffeine and . sodium benzoate is occasionally used as a respiratory stimulant in neonates. The drugs are somewhat selective in their actions at lower doses but tend to involve the entire CNS at higher doses. thereby producing mood elevation or euphoria. Halflife is 1 to 3 hours. dosages are listed in Drugs at a Glance: Central Nervous System Stimulants. hypertension) that are likely to be aggravated by the drugs. and substance abuse disorders as adolescents and adults as well as continuing difficulties in structured settings such as school or work. and other symptoms. Limitations include a short duration of action (5 to 10 minutes after a single intravenous [IV] dose) and therapeutic dosages near or overlapping those that produce convulsions. Some studies indicate that children with ADHD are more likely to have learning disabilities. It is well absorbed with oral administration and reaches peak plasma levels in 1 to 1. agitation. INDIVIDUAL CENTRAL NERVOUS SYSTEM STIMULANTS Individual drugs are described below. and gastritis. it also increases oxygen consumption and carbon dioxide production. but pharmacologic effects last 4 to 6 hours. increasing mental alertness and capacity for work. the drugs reduce behavioral symptoms and may improve cognitive performance. nervousness. They also are contraindicated in clients with anxiety or agitation. and prolonging wakefulness. Methylphenidate (Ritalin) is chemically related to amphetamines and produces similar actions and adverse effects. glaucoma. They are more important as drugs of abuse than as therapeutic agents. difficulty concentrating on a task. Amphetamines and Related Drugs Amphetamine. decreasing fatigue and drowsiness. These drugs are widely sold on the street and commonly abused (see Chap. resulting in increased heart rate and blood pressure. Dexmethylphenidate (Focalin) is very similar to methylphenidate and the amphetamines. below).252 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM not a prominent feature. 15). Its ability to promote wakefulness is similar to that of amphetamines and methylphenidate. insomnia. TYPES OF STIMULANTS Most CNS stimulants act by facilitating initiation and transmission of nerve impulses that excite other cells. and methamphetamine (Desoxyn) are closely related drugs that share characteristics of the amphetamines as a group. Amphetamines increase the amounts of norepinephrine. Although it increases tidal volume and respiratory rate. One analeptic is used occasionally to treat respiratory depression. the other one is approved only for treatment of narcolepsy. however. Endotracheal intubation and mechanical ventilation are safer and more effective in relieving respiratory depression from depressant drugs or other causes. They are usually contraindicated in clients with a history of drug abuse. peak plasma levels occur in about 2 hours with immediate-release tablets and about 5 hours with extended-release tablets. angina. produce signs of excessive CNS stimulation. increasing mental alertness and decreasing drowsiness and fatigue. Prescriptions for them are nonrefillable. slowed gastrointestinal motility. mood disorders. it also has Indications for Use Amphetamines and methylphenidate are used in the treatment of narcolepsy and ADHD. Amphetamines are Schedule II drugs under the Controlled Substances Act and have a high potential for drug abuse and dependence. such as restlessness. Dexmethylphenidate is indicated only for ADHD. Xanthines stimulate the cerebral cortex. Larger doses. In ADHD. and possibly serotonin in the brain. analeptics. or hyperthyroidism. Amphetamine-related drugs (methylphenidate and dexmethylphenidate) have essentially the same effects as the amphetamines and are also Schedule II drugs. Amphetamines also stimulate the sympathetic nervous system. but its mechanism of action is unknown. It is metabolized in the liver and excreted in urine. pupil dilation (mydriasis). anxiety. agitation.

PO 5 mg 1–2 times daily. >6 y: PO 5 mg once or twice daily initially. increase if necessary Narcolepsy: >6 y: PO 5 mg/d initially. coronary and peripheral vasodilation. It is rapidly absorbed (food may delay absorption). nausea. increase by 5 mg/d at weekly intervals until optimal response (usually no more than 40 mg/d) Narcolepsy: >6 y: PO 5 mg/d initially. increase by 5–10 mg at weekly intervals to a maximum of 60 mg/d if necessary Analeptics Doxapram (Dopram) Modafinil (Provigil) Narcolepsy IV 0. Modafinil is not recommended for patients with a history of left ventricular hypertrophy or ischemic changes on electrocardiograms. increase by 2. >6 y: PO 5 mg once or twice daily initially. PO 200 mg once daily. including CNS stimulation. increase by 5 mg/wk to effective dose ADHD: 3–5 y: PO 2. perception. Large amounts cause excessive CNS stimulation with anxiety. dizziness.CHAPTER 16 CENTRAL NERVOUS SYSTEM STIMULANTS 253 Drugs at a Glance: Central Nervous System Stimulants Routes and Dosage Ranges Generic/Trade Name Amphetamines Amphetamine Indications for Use Adults Children Narcolepsy ADHD Narcolepsy: PO 5–60 mg/d in divided doses Dextroamphetamine (Dexedrine) Narcolepsy ADHD Narcolepsy: PO 5–60 mg in divided doses Methamphetamine (Desoxyn) Amphetamine mixture (Adderall) Amphetamine-Related Drugs Dexmethylphenidate (Focalin) Methylphenidate (Ritalin. increase by 5 mg/wk to effective dose ADHD: 3–5 y: PO 2.5 mg/d initially. Metadate) ADHD in children ADHD Narcolepsy Narcolepsy: PO 10 mg daily initially. It is a Schedule IV drug. Xanthines Caffeine has numerous pharmacologic actions. skeletal muscle stimulation. Dosage should be reduced by 50% with se- vere hepatic impairment. Interactions with other drugs include decreased effects of cyclosporine and oral contraceptives and increased effects of phenytoin.5 mg/d initially.5 mg/min or more. Dosage not established for children <16 years of age psychoactive and euphoric effects that alter mood. in 2 divided doses >6y: ADHD. Dose by infusion should not exceed 3 g. hyperglycemia. chest pain. and warfarin. Steady-state concentrations are reached in 2 to 4 days and half-life with chronic use is about 15 hours. 15–25 mg daily. nausea. increased secretion of gastric acid and pepsin. and palpitations. in the morning.5 mg/d at weekly intervals until optimal response. insomnia. Adverse effects include anxiety. IV continuous infusion 5 mg/min initially. reaches peak plasma levels in 2 to 4 hours. nervousness. increased if necessary ADHD ADHD Narcolepsy Narcolepsy: PO 10–60 mg/d in 2 or 3 divided doses PO 2. diuresis.5–10 mg twice daily ≥6 y: ADHD. PO 5 mg twice a day initially.5 mg/d at weekly intervals until response. agitation. In low to moderate amounts. decreased to 2. effects of severe renal impairment are unknown. and thinking. tricyclic antidepressants. dysrhythmias. dyspnea. diarrhea. and bronchodilation from relaxation of smooth muscle. Ritalin SR. . Concerta. Usual dose. is 60% bound to plasma proteins. and is 90% metabolized by the liver to metabolites that are then excreted in urine. increase by 2. cardiac stimulation. cerebrovascular vasconstriction. caffeine increases alertness and capacity for work and decreases fatigue. headache. increase by 5 mg/d at weekly intervals until optimal response (usually no more than 40 mg/d) PO 5–10 mg daily initially. Dosage should be reduced by 50% with severe hepatic impairment. nervousness.5 mg/kg in single or divided doses. irritability.5–1.

caplet or geltab 32–33 60–65 1 tablet or capsule 200 1 tablet 100 Recommended dose 2 tablets 3 times daily (600 mg/d) 1 tablet 1 capsule 100 40 Recommended dose 2 tabs at onset of migraine. Guarana is widely used as a source of caffeine by soft drink manufacturers. the desired effect is bronchodilation and improvement of breathing. Vanquish APAP-Plus. toxicity may result from concomitant consumption of caffeine from several sources. psychiatric disturbances. tremors. CNS stimulation is then an adverse effect (see Chap. It is an ingredient in some nonprescription analgesic preparations and may increase analgesia.254 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM premature ventricular contractions. then 1 tab every hour if needed. With large amounts or chronic use. and vomiting. Midol OTC Antisleep Products Caffedrine. reproductive disorders. Diet Pepsi Mountain Dew Mr. energy drinks. Diet Sources of Caffeine Amount (oz) Caffeine (mg) Remarks 5–8 5–8 2 40–180 30–120 120 Caffeine content varies with product and preparation 8 8 12 80 50 70 Caffeine content varies with product and preparation 12 12 12 12 45 38 54 57 Most other cola drinks contain 35–45 mg/12 oz OTC Analgesics Anacin. dysrhythmias). and psychological dependence or habituation occurs. Excedrin. Pibb. a barbiturate. caffeine has been implicated as a causative or aggravating factor in cardiovascular disease (hypertension. peptic ulcers). The caffeine content of coffee and tea beverages is determined by the particular coffee bean or tea leaf and the method of preparation. Because of the widespread ingestion of caffeine-containing beverages and the wide availability of over-the-counter products that contain caffeine. Some authorities recommend that normal. up to 6/d (240 mg/d) Also contains butalbital. usually in combination with ephedra (ma huang). and most is consumed from dietary sources (eg. Theophylline preparations are xanthines used in the treatment of respiratory disorders. vit- TABLE 16–1 Source Coffee Brewed. hyperactivity and restlessness. A combination of caffeine and sodium benzoate is used as a respiratory stimulant in neonatal apnea unresponsive to other therapies. Toxic amounts may cause delirium and seizures. Diet Coke Pepsi. tea. carcinogenicity. Caffeine is usually prescribed as caffeine citrate for oral use and caffeine and sodium benzoate for parenteral use because these forms are more soluble than caffeine itself. Vivarin OTC Diuretic Aqua-Ban Prescription Drugs Cafergot Fiorinal 1 tablet or caplet 1 tablet. The main active ingredient is caffeine. 47). and is a Schedule III controlled drug . gastrointestinal disorders (esophageal reflux. Herbal and Dietary Supplements Guarana is made from the seeds of a South American shrub. Caffeine is a frequently consumed CNS stimulant worldwide. regular Instant Espresso Tea Brewed. up to 6 tabs (600 mg/attack) Recommended dose 1–2 cap every 4 hours. tachycardia. It is combined with an ergot alkaloid to treat migraine headaches (eg. Cafergot) and is the active ingredient in nonprescription stimulant (antisleep) preparations. healthy. leaf or bag Instant Iced Soft Drinks Coke. coffee. In these conditions. and drug abuse liability. Sources and amounts of caffeine are summarized in Table 16–1. nonpregnant adults consume no more than 250 mg of caffeine daily. Caffeine produces tolerance to its stimulating effects. osteoporosis (may increase loss of calcium in urine). NoDoz. It is also used as a flavoring agent and an ingredient in herbal stimulant and weight-loss products. and cola drinks). such as asthma and bronchitis. Pharmaceutical preparations include an oral preparation and a solution for injection. which is present in greater amounts than in coffee beans or dried tea leaves.

and IV diuretics (eg. When a CNS stimulant is prescribed. If cardiovascular collapse occurs. • Record weight at least weekly. PRINCIPLES OF THERAPY Appropriate Use Stimulant drugs are often misused and abused by people who want to combat fatigue and delay sleep. in people who are sensitive to the effects of caffeine or who have cardiovascular disease. Use of amphetamines or other stimulants for this purpose is not justified. which may also contain theophylline and theobromine. and minimize external stimulation. It is contraindicated during pregnancy and lactation and should be used cautiously. cardiac dysrhythmias. In general. insomia. These drugs are dangerous for drivers and those involved in similar activities. insomnia. As with caffeine from other sources. Try to identify potentially significant sources of caffeine. hallucinations. Evaluation • Reports of improved behavior and academic performance from parents and teachers of children with ADHD • Self. After emptying the stomach. assess behavior for signs of tolerance and abuse. place the client in a cool room. hypertension. Treatment is largely symptomatic and supportive. For any client receiving amphetamines or methylphenidate. . activated charcoal (1 g/kg) may be given. circulatory collapse. extracts. hyperactivity. if at all. the caffeine content of a guarana product is unknown and guarana may not be listed as an ingredient. coma. IV diazepam or lorazepam can be given to calm agitation. guarana may cause excessive nervousness and insomnia. high body temperature. fluid replacement and vasopressors may • Risk for Injury: Adverse drug effects (excessive cardiac and CNS stimulation. panic states. or street drugs). IV fluids. furosemide or mannitol) hasten drug excretion. is also available in teas. urinary acidification. restlessness. Assess for conditions that are aggravated by CNS stimulants. seizures. In general. • Provide information about the condition for which a stimulant drug is being given and the potential consequences of overusing the drug. students. combinations of stimulants. monitor cardiac function and temperature. or tachycardia. assess behavior as specifically and thoroughly as possible. combativeness. As a result. haloperidol may be given for symptoms of psychosis. or concurrent ingestion of a stimulant and another drug that slows the metabolism of the stimulant. such as long-distance drivers. delirium. capsules. Signs of toxicity may include severe agitation.CHAPTER 16 CENTRAL NERVOUS SYSTEM STIMULANTS 255 amin supplements. • Promote nutrition to avoid excessive weight loss. hyperactivity. weekends. • • • • • over-the-counter. consumers may not know how much caffeine they are ingesting in products containing guarana. Nursing Diagnoses • Sleep Pattern Disturbance related to hyperactivity. giving the smallest effective dose and limiting the number of doses obtained with one prescription decrease the likelihood of drug dependence or diversion (drug use by people for whom the drug is not prescribed). nervousness. or social environments for adolescents and adults with ADHD • Reports of decreased inappropriate sleep episodes with narcolepsy Nursing Process Assessment • Assess use of stimulant and depressant drugs (prescribed. tremors. With amphetamines. and athletes.or family reports of improved ability to function in work. and tablets of various strengths. insomnia Toxicity of CNS Stimulants: Recognition and Management Overdoses may occur with acute or chronic ingestion of large amounts of a single stimulant. or seizures. summers) to increase beneficial effects and help prevent drug dependence and stunted growth. The product. nervousness. Overall. irritability. and death. drug dependence) • Deficient Knowledge: Drug effects on children and adults • Noncompliance: Overuse of drug Planning/Goals The client will: • Take drugs safely and accurately • Improve attention span and task performance (children and adults with ADHD) and decrease hyperactivity (children with ADHD) • Have fewer sleep episodes during normal waking hours (for clients with narcolepsy) Interventions • For a child receiving CNS stimulants. For a child with possible attention deficit hyperactivity disorder (ADHD). Gastric lavage may be helpful if done within 4 hours of ingestion of the stimulant. the use of guarana as a CNS stimulant and weight-loss aid is not recommended and should be discouraged. elixirs. confusion. candies. assist parents in scheduling drug administration and drug holidays (eg. and chewing gums. alone or in combination with other central nervous system (CNS) stimulants. and they have no legitimate use in athletics. school. Assess caffeine intake as a possible cause of nervousness.

Concerta. IV diazepam or lorazepam may be used to control seizures. especially in children. and insomnia. and warfarin. and metabolic acidosis. Additional manifestations of caffeine toxicity include opisthotonus. heart palpitations. It may decrease effects of cyclosporine and oral contraceptives. dosage should be carefully titrated and monitored to avoid excessive CNS stimulation. muscle hypertonicity. fever. They should be swallowed whole. The risks of drug dependence are lessened if they are taken correctly. necessary resting mechanisms for the body. ylphenidate may increase effects of phenytoin and antidepressants (selective serotinin reuptake inhibitors and tricyclics). Treatment is symptomatic and supportive. muscle tremors or spasms. saline cathartics may be useful to remove undissolved drug granules. When used. Modafinil may increase effects of clomipramine. hyperglycemia. careful documentation of baseline symptoms over approximately 1 month is necessary to establish the diagnosis and evaluate outcomes of treatment. anorexia. and vomiting. and they may decrease effects of antihypertensive drugs. With caffeine. Use caution while driving or performing other tasks requiring alertness. Effects of CNS Stimulants on Other Drugs Caffeine may increase adverse effects of clozapine and theophylline by decreasing their metabolism and increasing their blood levels. phenytoin. ingestion of 15 to 30 mg/kg (1 to 2 g for a person of 70 kg or 150 lbs) may cause myocardial irritability. Guidelines for treatment of ADHD include the following: 1. decerebrate posturing. Oral doses of 5 g or more may cause death. before 6 PM. and Medadate ER are long-acting forms of methylphenidate. insomnia. ask the prescribing physician if the dose can be reduced or taken on a different schedule to relieve these adverse effects. Sprite and 7-Up have no caffeine. It may increase effects of aspirin by increasing aspirin absorption. and insomnia from excessive caffeine intake by decreasing consumption of coffee and other caffeine-containing beverages or by drinking decaffeinated coffee. Counseling and psychotherapy (eg. caloric intake (of nutritional foods) may need to be increased. impair physical coordination. ✔ Ritalin SR. ✔ Get adequate rest and sleep. Several cups of coffee may produce levels of 5 to 10 mcg/mL and symptoms of agitation and tremors. These are adverse drug effects and dosage may need to be reduced. Do not take stimulant drugs to delay fatigue and sleep. with gastric lavage and activated charcoal if indicated. Hemodialysis is indicated if the serum caffeine concentration is >100 mcg/mL or if life-threatening seizures or cardiac dysrhythmias occur. Dexmethylphenidate and meth- . vomiting. or skin rash. Self-Administration and Administration to Children ✔ Take regular tablets approximately 30 to 45 minutes before meals. hypokalemia. Medadate CD. nervousness. CNS stimulants may exacerbate symptoms. ✔ Avoid other central nervous system stimulants. This can be done by videotapes of behavior. and growth should be monitored at regular intervals during drug therapy. ✔ Take the last dose of the day in the afternoon. or caretakers. report excessive losses. and cola. Suppression of weight and height have been reported. ✔ Notify a health care provider of nervousness. tea. If a long-acting form of the stimulant drug has been ingested. ✔ If excessive weight loss. Cardiac dysrhythmias and seizures occur at higher levels. without crushing or chewing. parental counseling or family therapy) are recommended along with drug therapy for effective treatment and realistic expectations of outcomes. to avoid interference with sleep. These drugs have a high potential for abuse. observations and ratings by clinicians familiar with ADHD. ketosis. including caffeine.256 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM CLIENT TEACHING GUIDELINES Methylphenidate and Dexmethylphenidate General Considerations ✔ These drugs may mask symptoms of fatigue. In children with psychosis or Tourette syndrome. leukocytosis. tricyclic antidepressants. ✔ Take these drugs only as prescribed by a physician. and cause dizziness or drowsiness. anxiety. It may decrease effects of lithium by increasing lithium clearance. Signs of toxicity are correlated with serum levels of caffeine. parents. ✔ Record weight at least weekly. pulmonary edema. Some authorities believe that this condition is overdiagnosed and that stimulant drugs are prescribed unnecessarily. ✔ Prevent nervousness. In ADHD. tremors. Use in Children Central nervous system stimulants are not recommended for ADHD in children younger than 6 years of age. rhabdomyolysis with subsequent renal failure. these are normal. and by interviewing the child. ✔ The drugs may cause weight loss. or insomnia develops. be used.

Give amphetamines and methylphenidate early in the day. convulsions. b. c. An overdose may result. weight loss. Then. psychotic behavior b. As with most other drugs. If insomnia occurs. In addition. Metadate CD. In general. Use in Older Adults CNS stimulants should be used cautiously in older adults. Metadate ER. Some clinicians say they are indicated only if no significant problems occur during the drug-free pe- riod and are not recommended for most children. To minimize the drugs’ appetite-suppressing effects and risks of interference with nutrition and growth. Observe for therapeutic effects a. Dosage adjustments are often needed at least annually as the child grows and hepatic metabolism slows. Therapeutic effects depend on the reason for use. It is usually given daily. nervousness. hypertension c. Young children may not require treatment until starting school. which may be worse during the first 6 months of therapy. and better relationships with other children and family members. These reactions are more likely to occur with large doses. Older adults are likely to experience anxiety. NURSING ACTIONS NURSING ACTIONS Central Nervous System Stimulants RATIONALE/EXPLANATION 1. These reactions are caused by the sympathomimetic effects of the drugs. and interfere in social. diarrhea. 2. other dysrhythmias. nausea. gastritis. including dietary caffeine. and promote social development. constipation Adverse effects may occur with acute or chronic ingestion of any CNS stimulant drugs. give amphetamines and methylphenidate about 30 minutes before meals. tremors. facilitate learning. Drug holidays (stopping drug administration) are controversial. older adults often have cardiovascular disorders (eg. angina. reduced doses are safer in older adults. the drug-free periods decrease weight loss and growth suppression. Other clinicians believe they are desirable when children are not in school (eg. attention span. slowed metabolism and excretion increase the risks of accumulation and toxicity. Administer accurately a. In addition. Adverse effects include appetite suppression and weight loss. Gastrointestinal effects—anorexia. and quality and quantity of school work. academic. and mental confusion from excessive CNS stimulation. Cardiovascular effects—tachycardia. Observe for adverse effects a. To avoid interference with sleep. insomnia. Methylphenidate is the most commonly used drug. Breaking the tablets or capsules destroys the extended-release feature and allows the drug to be absorbed faster. or behavioral functioning. For children with attention deficit-hyperactivity disorder (ADHD). 4. summer) and necessary periodically to re-evaluate the child’s condition. are present for several months. insomnia. including weekends. Do not crush or open and instruct clients not to bite or chew long-acting forms of methylphenidate (Concerta. give the last dose of the day at an earlier time or decrease the dose. hypertension) that may be aggravated by the cardiac-stimulating effects of the drugs. (continued ) . for the first 3 to 4 weeks to allow caregivers to assess beneficial and adverse effects. at least 6 hours before bedtime. 3. anxiety. Desirable effects may include improvement in behavior. Drug therapy is indicated when symptoms are moderate to severe. drug therapy should be omitted or reduced in dosage when children are not in school. Fewer “sleep attacks” with narcolepsy b. nervousness.CHAPTER 16 CENTRAL NERVOUS SYSTEM STIMULANTS 257 2. When possible. Excessive central nervous system (CNS) stimulation— hyperactivity. Increased mental alertness and decreased fatigue 3. 5. Improved behavior and performance of cognitive and psychomotor tasks with ADHD c. the goal of drug therapy is to control symptoms. Ritalin SR). dysrhythmias.

phenytoin. fluvoxamine. and seizures occurring with stimulant overdose. Drugs that increase the alkalinity of the gastrointestinal tract increase intestinal absorption of amphetamines. Drugs that increase effects of caffeine: (1) Enoxacin. These drugs induce cytochrome P450 3A4 enzymes that partly metabolize modafinil. oral contraceptives h. Increased absorption and decreased excretion serve to potentiate drug effects. May impair caffeine metabolism. Drugs that decrease effects of modafinil: (1) Carbamazepine. rifampin g. and other signs of a hypertensive crisis. Drugs that decrease effects of amphetamines: (1) Acidifying agents (2) Antipsychotic agents e. ketoconazole f. theophylline (2) Cimetidine. Decrease or antagonize the excessive CNS stimulation produced by amphetamines. Drugs that decrease effects of CNS stimulants: (1) CNS depressants c. and urinary alkalinizers decrease urinary excretion. hyperactivity. antacids) RATIONALE/EXPLANATION Such combinations are potentially dangerous and should be avoided or minimized.258 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM NURSING ACTIONS 4. These drugs thereby increase the risks of headache. Drugs that increase the effects of CNS stimulants: (1) Other CNS stimulant drugs (2) Albuterol and related antiasthmatic drugs. These drugs inhibit the cytochrome P450 1A2 enzymes that participate in the metabolism of caffeine. subarachnoid hemorrhage. pseudoephedrine b. These drugs induce drug-metabolizing enzymes. Decreased absorption and increased excretion serve to decrease drug effects. Drugs that increase effects of amphetamines: (1) Alkalinizing agents (eg. (2) Monoamine oxidase (MAO) inhibitors d. rifampin . IV diazepam or lorazepam may be used to decrease agitation. thereby decreasing blood levels and increasing clearance of caffeine. Drugs that increase effects of modafinil: (1) Itraconazole. Potentiate amphetamines by slowing drug metabolism. Decreased metabolism may increase adverse effects. These drugs inhibit cytochrome P450 3A4 enzymes that partly metabolize modafinil. phenytoin. These drugs cause CNS and cardiac stimulating effects. Drugs that decrease effects of caffeine: (1) Carbamazepine. Chlorpromazine (Thorazine) or haloperidol (Haldol) is sometimes used in treating amphetamine overdose. Urinary acidifying agents (eg. The combination may cause death and should be avoided. mexilitene. ammonium chloride) increase urinary excretion and lower blood levels of amphetamines. Observe for drug interactions a.

(2001).. R. B. (1999). Clinical Pharmacokinetics.. T. 1247–1270. A. In E. and how may they be minimized? 5. (Ed. S. (2000). & Benitez. R. Do you think children taking CNS stimulants for ADHD should have drug-free periods? Justify your answer. T.. 1130–1134.CHAPTER 16 CENTRAL NERVOUS SYSTEM STIMULANTS 259 Review and Application Exercises 1. et al. A. (2001). 127–153. The medical letter handbook of adverse drug interactions. Attention-deficit/hyperactivity disorder (ADHD). . A. Louis: Facts and Comparisons. & Avila. 39(2). 7th ed. Inc. What is the rationale for treating narcolepsy and ADHD with CNS stimulants? 4.). New Rochelle. C. J. Spencer. J. Hovinga. PA: Springhouse Corporation. What are the major adverse effects of CNS stimulants. What kinds of behaviors may indicate ADHD? 3. Gourley (Eds. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. NY: The Medical Letter.) (2001). What kinds of behaviors may indicate narcolepsy? 2. (Updated monthly). Herfindal & D. J. 58(8). C. Wilens. T. Kim. J. Archives of General Psychiatry. R. Fetrow. St. SELECTED REFERENCES Carillo.. Drug facts and comparisons. 775–782. & Phelps. Textbook of therapeutics: Drug and disease management. 35(9). W. pp. Treatment of attention deficit hyperactivity disorder in children. Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder. The Annals of Pharmacotherapy. Philadelphia: Lippincott Williams & Wilkins. Kehoe. J. (2000). Biederman. Professional’s handbook of complementary & alternative medicines. Springhouse. W.

3 Drugs Affecting the Autonomic Nervous System .

and spinal cord. The autonomic nervous system is subdivided into the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS). Autonomic nerve impulses are carried through preganglionic fibers. A neurotransmitter is released from the terminal end of the preganglionic nerve allowing the nervous impulse to bridge the synapse between the preganglionic and postganglionic nerve. 5. blood vessels. The central nervous system includes the brain and spinal cord. Afferent neurons carry sensory input from the periphery to the CNS and modify motor output through the action of reflex arcs. The ANS is regulated by centers in the CNS. brain stem. Acetylcholine is synthesized from acetylcoenzyme A and choline and released at preganglionic fibers of both the SNS and PNS and at postganglionic fibers of the PNS. tyrosine → dopamine → norepinephrine → epinephrine). except in the adrenal medulla. Identify physiologic effects of the sympathetic nervous system. State names and general characteristics of drugs affecting the autonomic nervous system. AUTONOMIC NERVOUS SYSTEM The nervous system is composed of two main divisions. glands. The nerve fibers that secrete acetylcholine are called cholinergic fibers. Identify physiologic effects of the parasympathetic nervous system. ganglia. Norepinephrine is the end product. controls involuntary activities in the visceral organs of the body such as the heart. THE STUDENT WILL BE ABLE TO: 1. 5). The main neurotransmitters of the ANS are acetylcholine and norepinephrine (see Chap. Norepinephrine is synthesized from the amino acid tyrosine by a series of enzymatic conversions that also produce dopamine and epinephrine (ie. 4. 17–1). other visceral organs. The somatic nervous system innervates skeletal muscles and controls voluntary movement.chapter 17 Physiology of the Autonomic Nervous System Objectives AFTER STUDYING THIS CHAPTER. The efferent neurons carry motor signals from the CNS to the peripheral areas of the body. 3. 2. the central nervous system (CNS) and the peripheral nervous system (Fig. 5). Differentiate subtypes and functions of parasympathetic nervous system receptors. and smooth muscle (Fig. The peripheral nervous system is subdivided into the afferent neurons and efferent neurons. 17–2). The efferent portion of the peripheral nervous system is further subdivided into the somatic and autonomic nervous system (ANS). Preganglionic impulses travel from the CNS along the preganglionic nerves to ganglia. Ganglia are composed of the terminal end of the preganglionic nerve and clusters of postganglionic cell bodies. smooth muscle. and to repair body tissues. The ANS. The postganglionic impulses travel from ganglia to effector tissues of the heart. without conscious thought or effort. Describe signal transduction and the intracellular events that occur when receptors of the autonomic nervous system are stimulated. and postganglionic fibers. Acetylcholine is also released from postganglionic sympathetic neurons that innervate the sweat glands and from motor neurons of the somatic nervous system that innervate the skeletal muscles. Nerve impulses are generated and transmitted to body tissues in the sympathetic and parasympathetic nervous systems as they are in the CNS (see Chap. Differentiate subtypes and functions of sympathetic nervous system receptors. These functions can be broadly described as activities designed to maintain a constant internal environment (homeostasis). including the hypothalamus. Norepinephrine is released at most postganglionic fibers of the 261 . and secretory glands. where most of the norepinephrine is converted to epinephrine. The peripheral nervous system includes all the neurons and ganglia found outside the CNS. 6. to respond to stress or emergencies.

262 SECTION 3 DRUGS AFFECTING THE AUTONOMIC NERVOUS SYSTEM The Human Nervous System Central Nervous System (CNS) (brain and spinal cord) Peripheral Nervous System (neurons and ganglia outside the brain and spinal cord) Afferent (sensory) Neurons Efferent (motor) Neurons Somatic Nervous System (voluntary) Autonomic Nervous System (ANS) (involuntary) Sympathetic Nervous System (SNS) (adrenergic) Figure 17–1 Divisions of the human nervous system. Parasympathetic Nervous System (PNS) (cholinergic) Muscarinic receptors Parasympathetic ganglion Acetylcholine Parasympathetic nervous system (PNS) Presynaptic neuron Acetylcholine Heart Blood vessels Glands Visceral organs Smooth muscle Muscarinic receptors Sweat glands Dopamine Postsynaptic neuron Sympathetic nervous system with sympathoadrenal branch Nicotinic receptors Norepinephrine Acetylcholine Alpha. Beta receptors Heart Blood vessels Glands Visceral organs Smooth muscle Adrenal medulla (nicotinic receptors) Epinephrine and norepinephrine Nicotinic receptors Skeletal muscle Acetylcholine Figure 17–2 Organization of the autonomic and somatic nervous systems. Nicotinic receptors Postsynaptic neuron Acetylcholine Presynaptic neuron Sympathetic ganglion Dopamine receptors Renal vascular smooth muscle Somatic nervous system .

most organs are predominantly controlled by one system. produce lipolysis (thermogenesis). alpha2. These receptors have been further subdivided into alpha1. dopamine is essential for normal function (see Chap. sympathetic stimulation of the heart causes an increased rate and force of myocardial contraction. Stimulation of both systems causes excitatory effects in some organs but inhibitory effects in others. It exerts intense but brief effects on presynaptic and postsynaptic adrenergic receptors. thereby resting the heart. receptor activation by the ligand) and resulting events that will occur inside the cell. such as strenuous exercise or work. Exceptions to this antagonistic action include sweating and regulation of arteriolar blood vessel diameter. Most of the norepinephrine is taken up again by the nerve endings and reused as a neurotransmitter. Specific body responses include: 1. is often called the fight-or-flight reaction. this ligand–receptor interaction activates a cell membrane-bound G protein and an effector enzyme that then activate a molecule inside the cell called a second messenger. and animal studies suggest that drugs targeted to this receptor may augment heat production. its main effects are on the heart and blood vessels of the renal system and viscera. Increased rate and depth of respiration 10. and increasing intracellular calcium levels. and increase energy expenditure. Norepinephrine is synthesized in adrenergic nerve endings and released into the synapse when adrenergic nerve endings are stimulated. These hormones are metabolized mainly in the liver by the enzymes MAO and COMT. in peripheral tissues. Norepinephrine also functions as a hormone. which is norepinephrine. or it is metabolized by monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT). which was not taken back into the nerve endings. pain. The ligand that binds the receptor is the so-called first messenger. In response to adrenergic nerve stimulation. A beta3 receptor has been identified. beta1.CHAPTER 17 PHYSIOLOGY OF THE AUTONOMIC NERVOUS SYSTEM 263 SNS. Norepinephrine acts mainly on alpha receptors. medications. which is controlled by the SNS. Increased rate of blood coagulation 9. Increased muscle strength 8. The larger proportion of the circulating hormones (approximately 80%) is epinephrine. 5). When receptors located on target tissues are stimulated by a ligand. This second messenger is the link between events that are occurring outside the cell (ie. parasympathetic stimulation decreases rate and force of contraction. skin. and skeletal muscles. Only dopamine can activate . the effects last longer because the hormones are removed from the blood more slowly. along with epinephrine. hyperglycemia. Increased rate of cellular metabolism—increased oxygen consumption and carbon dioxide production 4. The remainder of the norepinephrine. They are continually present in arterial blood in amounts that vary according to the degree of stress present and the ability of the adrenal medullae to respond to stimuli. Nerve fibers secreting norepinephrine are called adrenergic fibers. diffuses into surrounding tissue fluids and blood. a cascade of intracellular events known as signal transduction is initiated. and beta2 receptors. Increased capacity for vigorous muscle activity in response to a perceived threat. The intensity and duration of responses depend on the amounts of norepinephrine and epinephrine present. Increased mental activity and ability to think clearly 7. The two divisions of the ANS are usually antagonistic in their actions on a particular organ. There are no beta3 agonist compounds approved by the Food and Drug Administration for human use. Increased sweating. However. In the brain. hemorrhage. This reuptake can be inhibited by cocaine and tricyclic antidepressant medications and is responsible for the activation of the sympat