Chapter 18 - Pharm

Chapter 18:
Autocoids and Antihistamines
Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Chapter 18 Outline
Autocoids and antihistamines

Histamine (H1 or H2) Antihistamines (H1-receptor antagonists) Peripheral (nonsedating) H1-receptor antagonists Other autocoids
Autocoids and Antihistamines
Haveles (p. 234)
Autocoids all occur naturally in the body, are produced by many tissues, and are formed by the tissues on which they act
Agonists or antagonists include H1- and H2receptor antagonists (H-RAs) or blockers, the eicosanoids (prostaglandins [PGs], thromboxanes [TXs], and leukotrienes [LTs]), serotonin agonists, angiotensin inhibitors, and cytokinins
Histamine
Haveles (pp. 234-235)
Pharmacologic effects Adverse reactions Uses
contd
Histamine
Haveles (pp. 234-235) (Fig. 18-1) Almost all mammalian tissues contain or can synthesize histamine
A ubiquitous biogenic amine
In humans, histamine is stored in mast cells, intestinal mucosa, and in the central nervous system (CNS) (mast cell in tissue = basophil in the bloodstream)
During an allergic reaction, mast cells degranulate and histamine is released

Copyright 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. 5
Pharmacologic Effects of Histamine
Haveles (p. 234)
H1-agonist effects: vasodilation, increased capillary permeability, bronchoconstriction, and pain or itching in cutaneous nerve endings H2-agonist effects: increased gastric acid secretion
contd
Pharmacologic Effects of Histamine
Agents that block or antagonize the effects of histamine at the H1-receptors are known as H1-blockers or H1-RAs, and at the H2receptors they are H2-blockers or H2-RAs
Adverse Reactions of Histamine
Haveles (p. 235)
When an allergic reaction occurs, an antibodyantigen reaction causes release of histamine and other autocoids Anaphylaxis is a serious and sometimes fatal reaction to a foreign protein or drug introduced into the body
Anaphylaxis may involve difficulty in breathing due to bronchoconstriction, convulsions, lapses into unconsciousness, and death The predominant feature is bronchoconstriction
contd
Other effects involve vasodilation and increased capillary permeability, both of which lead to decreased blood pressure followed by shock and cardiovascular collapse
contd
The drug of choice for anaphylaxis is parenteral epinephrine
A physiologic antagonist that dilates bronchioles via 2-receptors rather than an antihistamine An antihistamine is a pharmacologic antagonist that
blocks bronchoconstriction produced by histamine at the same H1-receptor Antihistamines antagonize only some of the effects of histamine, and they work competitively, whereas epinephrine acts as a direct 2-agonist
10
Uses of Histamine
Haveles (p. 235)
No clinical uses of histamine have been established
11
Antihistamines (H1-Receptor Antagonists)
Pharmacologic effects Adverse reactions Toxicity Uses
contd
12
Antihistamines (H1-Receptor Antagonists)

Haveles (p. 235)
Antihistamine refers to agents that are

H1-RAs or H1-receptor blockers
Many patients have seasonal allergic reactions A mild allergic reaction to a drug may be treated with antihistamines Patients taking antihistamines may experience side effects such as xerostomia Antihistamines interact with many other drug groups and are additive with other CNS depressants
13
Pharmacologic Effects of Antihistamines
Haveles (pp. 235-236) (Fig. 18-2; Table 18-1)
Older H1-RAs have several pharmacologic effects, including antihistaminic, anticholinergic, antiserotonergic, and sedative effects
Effects can be divided into those caused by blocking histamine at the H1-receptor and those independent of this effect
14
H1-Receptor Blocking Effects of Antihistamines
Haveles (p. 235) Drugs that are H1-antagonists competitively block or antagonize histamines effect at the following sites Capillary permeability: blocking capillary permeability produced by histamine reduces tissue edema Vascular smooth muscle (vessels): antihistamines block dilation Nonvascular (bronchial) smooth muscle: because other autocoids are also released in an anaphylactic reaction, antihistamines are not effective in counteracting all the bronchoconstriction present Nerve endings: antihistamines can suppress itching and pain associated with histamine-mediated reaction at cutaneous nerve endings
Other Effects (Unrelated to H1-Blocking Effects) of Antihistamines
CNS: antihistamines produce varying degrees of CNS depression (may be used to induce sleep) Anticholinergic: can be used to dry up secretions Antiemetic: some antihistamines, such as meclizine (Dramamine, Bonine), have pronounced antiemetic or antimotion sickness activity
Also effective in controlling dizziness, nausea, and vomiting with Mnires syndrome
Local anesthesia: may be used to provide some local anesthesia

Adverse Reactions of Antihistamines
Haveles (pp. 236-237) (Fig. 18-2)
Vary in relative amounts among the different agents CNS depression: can be a pharmacologic effect or adverse reaction
Sedation is the most common side effect associated with older antihistamines; may be accompanied by dizziness, tinnitus, incoordination, blurred vision, and fatigue When antihistamines are combined with decongestants, CNS depression of the antihistamine is counteracted by CNS stimulation of the decongestant
contd
Adverse Reactions of Antihistamines
Gastrointestinal (GI) complaints associated with antihistamines include anorexia, nausea, vomiting, and constipation Anticholinergic: H1-RAs have varying anticholinergic effects
Anticholinergic effects lead to xerostomia
18
Toxicity of Antihistamines
Haveles (p. 237)
Antihistamine poisoning has become more common in recent years

Excitation predominates in small children, and sedation can occur in adults Death usually results from coma with cardiovascular and respiratory collapse
19
Uses of Antihistamines
Allergic reactions: allergic rhinitis and seasonal hay fever can be controlled by antihistamines
Acute urticarial attacks can be treated
Nausea and vomiting: used to prevent and treat motion sickness and to control postoperative vomiting and vomiting induced by radiation therapy
contd
Uses of Antihistamines
Preoperative sedation: because of their sedative effects Over-the-counter sleep aids: diphenhydramine (Nytol) is used in over-the-counter sleep aids Local anesthesia: diphenhydramine (Benadryl) can be used by injection to provide some local anesthesia
21
Examples of Antihistamines
Haveles (p. 236) (Table 18-1) diphenhydramine (Benadryl) carbinoxamine (Clistin) clemastine (Tavist)
Ethanolamines

Ethylenediamines
tripelennamine (PBZ) pyrilamine (various)

contd
22
Haveles (p. 236) (Table 18-1) chlorpheniramine (Chlor-Trimeton) dexchlorpheniramine (Polaramine) brompheniramine (Dimetane)
Alkylamines

Phenothiazines
promethazine (Phenergan)
contd
23
Haveles (p. 236) (Table 18-1) cyproheptadine (Periactin) azatadine (Optimine) phenindamine (Nolahist)
Piperadines

Piperazines
hydroxyzine (Vistaril, Atarax)
24
Peripheral (Nonsedating) H1Receptor Antagonists
Haveles (pp. 226, 238) (Table 18-1)
No common chemical denominator, they are different in origin, chemical structure, solubility, and metabolic effects
All block peripheral H1-receptors
Do not cross the blood-brain barrier, do not produce sedation

contd
25
Peripheral (Nonsedating) H1Receptor Antagonists
Haveles (p. 236)
fexofenadine (Allegra): an active metabolite of terfenadine (Seldane)
Side effects include drowsiness and viral infections
loratadine (Claritin) desloratadine (Clarinex) cetirizine (Zyrtec) acrivastine (Semprex) azelastine (Astelin)
Other Autocoids
PGs and TXs LTs Kinins Substance P
27
Prostaglandins and Thromboxanes
Members of a group of biologically active agents termed eicosanoids
Produced in the body in response to many different stimuli and small quantities produce a large spectrum of effects on many different body systems
28
Pharmacologic Effects of Prostaglandins
Not only is there a wide spectrum of action, but also different PGs have different activities in different tissues

Smooth-muscle effects: vascular smooth muscle may be relaxed or stimulated, depending on the specific PGs Platelets: TX stimulates platelet aggregation and is a vasoconstrictor; PGI inhibits platelet aggregation and is a vasodilator Effects on reproductive organs: both PGE and PGF have oxytocic action CNS: PGs increase body temperature by releasing interleukin-1 Other effects: increased heart rate and cardiac output
Dental Implications
Haveles (p. 239)
PGs have been implicated in periodontal disease
At least two stages of periodontal disease may involve PGs The first is inflammation of the gingiva with erythema,
edema, and increase in gingival exudate The second is the resorption of alveolar bone with tooth loss
30
Uses of Prostaglandins
Haveles (p. 239)
PGs may be used for inducing midtrimester abortions A PG agonist (misoprostol [Cytotec]) is available for prevention of nonsteroidal antiinflammatory agentinduced ulcers PGs are being studied in treatment of bronchial asthma and hypertension
31
Prostaglandin Antagonists
Haveles (p. 239)
Administration of PG antagonists may prove useful in the treatment of certain pathologic conditions

Aspirin can inhibit platelet aggregation by blocking TX Indomethacin blocks the effects of PGs on ductus arteriosus
32
Leukotrienes
Haveles (p. 239)
Another complex group of autocoids that are also derived from arachidonic acid

Cause strong bronchoconstriction in humans They also contract other smooth muscle such as the uterus and GI tract
33
Kinins
Polypeptides that are distributed in a great variety of body tissues
Kallidin and bradykinin are found in plasma and may play a role in dental diseases
Plasma kinins may be involved in shock and acute or chronic allergic or inflammatory conditions such as anaphylaxis and arthritis
34
Substance P
Haveles (p. 240)
A peptide thought to function as a neurotransmitter in the CNS and a local hormone in the GI tracts

A vasodilator and produces hypotension Increases the action of the intestinal and bronchial smooth muscle Causes secretion in the salivary glands
35

Chapter 18 - Pharm

Cargado por

Información del documento

Derechos de autor

Formatos disponibles

Compartir este documento

Compartir o incrustar documentos

Opciones para compartir

¿Le pareció útil este documento?

¿Este contenido es inapropiado?

Copyright:

Formatos disponibles

Chapter 18 - Pharm

Cargado por

Copyright:

Formatos disponibles

Chapter 18:

Autocoids and Antihistamines

Autocoids and antihistamines

Autocoids and Antihistamines

Haveles (p. 234)

Haveles (pp. 234-235)

Pharmacologic effects Adverse reactions Uses

A ubiquitous biogenic amine

During an allergic reaction, mast cells degranulate and histamine is released

Pharmacologic Effects of Histamine

Haveles (p. 234)

Pharmacologic Effects of Histamine

Haveles (pp. 234-235)

Adverse Reactions of Histamine

Haveles (p. 235)

Adverse Reactions of Histamine

Adverse Reactions of Histamine

The drug of choice for anaphylaxis is parenteral epinephrine

Haveles (p. 235)

No clinical uses of histamine have been established

Antihistamines (H1-Receptor Antagonists)

Haveles (pp. 235-238)

Pharmacologic effects Adverse reactions Toxicity Uses

Antihistamines (H1-Receptor Antagonists)

Haveles (p. 235)

Antihistamine refers to agents that are

Pharmacologic Effects of Antihistamines

Haveles (pp. 235-236) (Fig. 18-2; Table 18-1)

H1-Receptor Blocking Effects of Antihistamines

Other Effects (Unrelated to H1-Blocking Effects) of Antihistamines

Haveles (pp. 235-236)

Local anesthesia: may be used to provide some local anesthesia

Adverse Reactions of Antihistamines

Haveles (pp. 236-237) (Fig. 18-2)

Adverse Reactions of Antihistamines

Anticholinergic effects lead to xerostomia

Haveles (p. 237)

Antihistamine poisoning has become more common in recent years

Haveles (pp. 237-238)

Acute urticarial attacks can be treated

Haveles (pp. 237-238)

tripelennamine (PBZ) pyrilamine (various)

hydroxyzine (Vistaril, Atarax)

Peripheral (Nonsedating) H1Receptor Antagonists

Haveles (pp. 226, 238) (Table 18-1)

All block peripheral H1-receptors

Do not cross the blood-brain barrier, do not produce sedation

Peripheral (Nonsedating) H1Receptor Antagonists

Haveles (p. 236)

fexofenadine (Allegra): an active metabolite of terfenadine (Seldane)

Side effects include drowsiness and viral infections

Haveles (pp. 238-240)

PGs and TXs LTs Kinins Substance P

Prostaglandins and Thromboxanes

Haveles (pp. 238-239)

Members of a group of biologically active agents termed eicosanoids

Pharmacologic Effects of Prostaglandins

Haveles (pp. 238-239)

Haveles (p. 239)

PGs have been implicated in periodontal disease

Haveles (p. 239)

Haveles (p. 239)

Haveles (p. 239)

Haveles (pp. 239-240)