Pharmacology of the GIT

The mouth a proper flow of saliva is necessary to keep the mouth fresh & free from infection. Salivary flow will be diminished in fever, dehydration ,& by certain drugs. Several oral infection may supervene if salivary flow is markedly decreased.

Prevention of oral infection

Avoid oral infection during surgery Avoid dehydration Use mouthwashes

1. 2. 3.

The major components of mouthrinses:

1. Water: the major vehicle to solubilize the ingredients. 2. Flavoring: is designed to make mouthrinse pleasant to use. 3. Humectant: to prevent crystallization around the opening of the container.

4.Surfactant: to solubilize the flavoring agent & provide foaming action. 5. Alcohol is also helps solubilize some of the ingredients present in the formulation. 6. Active ingredients vary within the product category antimicrobial agents, fluoride, astringent salts & chlorophyllins

Chlorophyllins can serve as topical deodorizers to mask halitosis. Fluoride rinses will reduce carious lesions.

chlorhexidine broad spectrum antibacterial agent Depending on the dose, it can interfere with bacterial cell wall transport or disrupt the cell wall.
Is used in 0.2% solution , the mouth is rinsed 2 to 3 times daily with about 10 ml for 1 minute. The tongue & teeth may be stained brown but this can be avoided by brushing the teeth before use.
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General dosing information: The usual adult dose is 10-20 ml. the duration of rinsing varies depending on the type of agent used. The maximal dose for each patient must be individualized depending on factors as age, physical status, ability to effectively rinse & expectorate, oral health & sensitivity. Mouthwashes are often not prescribed for young pediatrics. Reduced maximum doses may be indicated for geriatric patients
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Patient advise
The effectiveness of any mouhrinse is tied to the use of the agent as prescribed by the dentist. To receive the greatest antiplaque or anticaries benefit, the patient should rinse before retiring to bed

After using the mouthwash , the patient should not rinse with water or drink anything for at least 30 minutes, immediately drinking or rinsing with water will increase the drug clearance from the mouth & reduce its effectiveness.

Peptic Ulcer Disease

Definition Break & discontinuity of the mucosa of the stomach or duodenum, penetrating into muscularis mucosa Factors 1. Infection with Helicobacter Pylori (H.Pylori) 2. Increased HCL secretion 3. Inadequate mucosal defense against gastric acid 4. Other factors: smoking, NSAIDs, alcohol
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Treatment: Aim 1. Symptomatic relief 2. Prevent relapse 3. Prevent complication

Non pharmacological approaches 1. Stop smoking 2. Avoid alcohol 3. Stop the use of ulcerogenic drugs (NSAIDs)

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Pharmacological 1. Eradicate H.Pylori 2. Reduce or neutralize the acid 3. Protect the gastric mucosa from damage

Eradication of Infection H.Pylori adapted to live in the mucus that overlies gastric epithelial cells & mucosa in the duodenum Gram -ve bacteria that produces enzymes which cause tissue damage

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H. pylori

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Optimal therapy of patient with peptic ulcer (duodenal & gastric ulcers) who are infected with H.Pylori requires antimicrobial treatment

Various drug combination which are effective: Omeprazole (antisecretory) Antibiotic like Clarithromycin, Amoxicillin, Tetracycline & Metronidazole

Triple therapy Regimen Omeprazole or Lanzoprazole + Amoxicillin + Clarithromycin.

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Eradication of H.Pylori results in rapid healing of active peptic ulcer & low recurrence rates (less than 15% compared to 60 to 100% per year for patients used traditional antisecretory agents)

2. Reduction of Acidity This can be done by inhibit H+ secretion or neutralize H+ Gastric acid secretion by parietal cells of the gastric mucosa is controlled by:
1. Acetylcholine 2. Histamine 3.Gastrin

they stimulate H+

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4. Prostaglandins (PGs) E2 & I2 inhibit acid secretion, stimulate mucus & bicarbonate secretion.
A. Drugs Used to Inhibit H+ Secretion 1.Histamine antagonists (H2-receptor antagonists) MOA: blocks histamine receptors inhibit H+ secretion

Examples: Cimetidine, Ranitidine

Indications: 1. Peptic ulcer 2. Gastroesophageal reflux disease

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Unwanted effects are rare.

Cimetidine sometimes gynaecomastia in men & rarely, a decrease in sexual function. Cimetidine also inhibits cytochrome P450 and retard metabolism of a range of drugs.

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2.Proton Pump Inhibitors (PPIs)

MOA: bind to H+/K+ -ATPase enzyme system, suppressing secretion of H+ ions into gastric lumen Examples: Omeprazole, Lanzoprazole

Indications: 1.As one component of therapy for eradication of H.Pylori. 2.Treatment of NSAIDs induced ulcer.

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3. Anti-muscarinic Drugs Specific muscarinic M1-receptor antagonists: Pirenzepine

Antacids They are weak bases, they reduce gastric acidity by neutralization Commonly used antacids are salts of Aluminum & Magnesium as Al(OH)3, Mg(OH)2 either alone or in combination; NaHCO3, CaCO3 also used

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Therapeutic uses: For symptomatic relief of peptic ulcer disease & GRED S/Es:

1. Mg-containing antacids cause diarrhea 2. Al-containing antacids cause constipation 3.NaHCO3 librates CO2 causing belching & flatulence. Should not be given to patients who are on a sodiumrestricted diet.

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B. Mucosal Protective Agents 1.Sucralfate It is combination of Al salts & sulfated sucrose MOA: In acidic medium, it forms complex gel with mucus, so creates a physical barrier that impairs diffusion of HCL Sucralfate should not be administered with antacids, H2-antagonists or PPIs

S/Es: Constipation

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2.Misoprostol MOA Stable analogue of PGE1, it inhibit gastric acid secretion It is used to prevent gastric damage that can occur with chronic use of NSAIDs

S/Es: Diarrhea,Uterine contraction may occur

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Anti-emetic Agents Nausea & vomiting may occur in variety of conditions, for examples:
1. Motion sickness 2. Hepatitis 3. Chemotherapeutic agents 4. Pregnancy

Uncontrolled vomiting can produce dehydration, metabolic imbalance & nutrients depletion

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Receptors mediate emesis:

1. Histamine receptors [H1] 2. Dopamine receptors [D2] 3. 5-HT3 (serotonin) receptors 4. Muscarinic receptors

Anti-emetic classified as antihistamine, anticholinergic, anti-dopaminergic, anti-5-HT3 drugs

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Drug class
D2-receptor antagonists

example
Metoclopramide

Histamine [H1] Receptor Antagonists

Cyclizine

5-HT3 Receptor Antagonists

Ondansetron

Antimuscarinic Agents

Hyoscine

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Antidiarrheal Agents Diarrhea: frequent passage of liquid feces Pathophysiology of diarrhea 1. motility of GIT 2. secretion of fluid into GIT lumen 3. fluid absorption in the intestine Causes of diarrhea 1. Infections 2.Toxins 3.Drugs

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Treatment 1.Maintenance of fluid & electrolyte balance Oral rehydration is the 1st priority

2. Use of Anti-infective agents

3. Use of Non-antimicrobial Antidiarrheal agents (Antimotility) a. Antimuscarinic agents

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b. Opiates 1. Codeine 2. Loperamide

S/Es of antimotility agents: constipation.

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Purgatives (laxatives) Constipation: refers to bowel movements that are infrequent and/or hard to pass Causes: 1. Pregnancy 2. Drugs 3. Elderly patients 4. Diet contents

Treatment: 1. Remove the cause 2. Accelerate the movement of food through GIT by several methods:

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The routine use of laxatives is discouraged, as having bowel movements may come to be dependent upon their use.
Classes
Bulk laxatives

Examples
Methylcellulose

Osmotic laxatives Lactulose Fecal softener Stimulant Purgatives Glycerin suppositories Bisacodyl
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