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PEPTIC ULCER Definitions: Stomach or duodenal mucosal lesions

PEPTIC ULCER Definitions: Stomach or duodenal mucosal lesions Occurrence: due to imbalance between aggressive factors and mucosal protective mechanisms. PEPTIC ULCER Aggressive factors Pepsin secretion - acid secretion Protective factors Prostaglandins (E2 & I2 )

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PEPTIC ULCER Definitions: Stomach or duodenal mucosal lesions

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  1. PEPTIC ULCER Definitions: Stomach or duodenal mucosal lesions Occurrence: due to imbalance between aggressive factors and mucosal protective mechanisms.

  2. PEPTIC ULCER Aggressive factors Pepsin secretion - acid secretion Protective factors Prostaglandins (E2 & I2 ) Mucus/bicarbonate secretion Mucosal blood flow Rapid turnover of gastric mucosa

  3. Risk factors • H Pylori infections • Alcohol • Smoking • Diet • Drugs (NSAIDs, corticosteroids). • Stress • Genetic factors • Diseases (Zollinger Ellison Syndrome).

  4. SYMPTOMS: • Nausea – Vomiting – Anorexia • Upper abdominal pain. • Weight loss. • Heart burn.

  5. COMPLICATIONS: Gastrointestinal hemorrhage Chronic iron deficiency anemia Pyloric stenosis Perforation

  6. Gastric secretions • Pepsinogens (Chief cells). • HCl and intrinsic factor (Parietal cells). • Gastrin (G-cells). • Mucus, bicarbonate (mucus-secreting cells).

  7. Regulation of Gastric secretions Histamine (local hormone) Acetylcholine (neurotransmitter). Gastrin (hormone).

  8. AIMS OF ULCER TREATMENT • Promotion of ulcer healing. • Symptomatic relief of pain. • Prevention of recurrence (relapse). • Prevention of complications

  9. DRUG TREATMENT OF PEPTIC ULCER I. Gastric hyposecretory drugs. • H2 receptor blockers • Muscarinic receptor blockers • Proton pump inhibitors II. Eradication of H. pylori infections To prevent relapse

  10. DRUG TREATMENT OF PEPTIC ULCER III. Mucosal cytoprotective agents. Sucralfate Colloidal bismuth Prostaglandin analogues IV. Neutralizing agents (antacids).

  11. Gastric hyposecretory drugs • H2 receptor blockers • Muscarinic receptor blockers • Proton pump inhibitors • Decreasing gastric acidity can reduce absorption of ketoconazole & iron preparation, digoxin.

  12. Proton Pump Inhibitors Mechanism of action Irreversible inhibition of proton pump (H+/ K+ ATPase) that is responsible for final step in gastric acid secretion from the parietal cell. PP inhibitors include: Omperazole Lansoprazole Pantoprazole

  13. Illustration of Gastric secretion by parietal cells

  14. Pharmacokinetics: They are prodrugs – taken orally. are given as enteric coated capsules They are rapidly absorbed from the intestine. They are activated in the acidic medium of the secretory parietal cell canaliculus. They are inactivated if (combined with H2 receptor blockers).

  15. Have long duration of action (> 12 h-24 h). Once daily dose is sufficient Bioavailability is reduced by food. Given 1 h before meal. Are metabolized in the liver by CytP450. They are more potent than H2 receptor blockers Inhibits basal and stimulated-acid secretion. Dose reduction is required in severe liver failure.

  16. USES 1. Zollinger Ellison syndrome (First choice). 2. Resistant severe peptic ulcer ( 4-8 weeks). 3. Reflux esophagitis. 4. Eradication of H. pylori.

  17. ADVERSE EFFECTS GIT disturbances: nausea, vomiting, diarrhea Achlorhydria. Hypergastrinaemia Gastric hyperplasia. Increased bacterial flora (nitrosamine)

  18. H2 receptor blockers Mechanism of action They competitively and reversibly block to H2 receptors on the parietal cells thus reduce gastric secretion. They include: Cimetidine Ranitidine Famotidine Nizatidine

  19. Pharmacokinetics Good oral absorption Plasma half life (1-3 h). Duration (4-12 h). First pass metabolism (50% Except Nizatidine 100 % bioavailability). Given before meals. Metabolized by liver. Excreted mainly in urine. Cross placenta & excreted in milk

  20. Pharmacological actions: Inhibit histamine, gastrin, cholinergic drug -induced secretions. Reduce basal and food-stimulated gastric secretion. Reduce pepsin activity. Promote mucosal healing & decrease pain

  21. USES: • Duodenal Ulcer (6-8 weeks). • Benign gastric ulcer (8-12 weeks). • Reflux esophagitis • Zollinger Ellison Syndrome (large doses). • Pre-anesthetic medication (To prevent • aspiration pneumonitis). • Eradication of H. pylori infections.

  22. Adverse Effects of H2 blockers: GIT disturbances: nausea, vomiting CNS effects: Headache, dizziness, confusion (elderly – renal or hepatic dysfunction). CVS effects Bradycardia and hypotension (rapid I.V.)

  23. Cimetidine has other adverse effects: • Endocrine effects • Antiandrogenic actions (gynecomasteia – impotence) • Galactorrhea in women. • Cytochrome P450 inhibitor: decrease metabolism of oral anticoagulant, phenytoin, benzodiazepines.

  24. Precautions Maintenance dose (Relapse may occur). Dose reduction in severe renal or hepatic failure and elderly.

  25. ANTICHOLINERGIC DRUGS 1. Non selective muscarinic blockers: Oxyphenonium, dicyclomine • Decreased gastric motility • Delayed gastric emptying - Heart burn - Atropine like side effects.

  26. 2. Selective muscarinic blockers: Pirenzepine - Telenzepine • Blocks M1 receptors on the parietal cells. • Selectively inhibit gastric acid secretion • No effect on gastric motility • Less side effects of cholinergic blockade. • No effect on CNS. • Dose : 50 mg bid for 4-6 weeks Uses 1.Adjuvants to H2 receptor blockers. 2. decrease nocturnal pain in peptic ulcer.

  27. Eradication Of H Pylori • Is a bacteria that causes chronic inflammation of the inner lining of the stomach. • Produce enzymes (tissue damage), inflammation – ulcer. • Duodenal ulcer - Gastric ulcer • Risk factor for esophagus and stomach cancers. • Eradication is important to prevent recurrence of ulcer.

  28. Helicobacter pylori in association with gastric mucosa

  29. Treatment • Combined therapy is usually used. • Clarithromycin, tetracycline, amoxicillin • Proton pump inhibitors or H2 receptor blockers. • Bismuth compounds • Metronidazole. • Resistance may develop to antibiotics. • Better eradication is obtained using proton pump inhibitors & clarithromycin.

  30. Treatment The standard first-line therapy is "triple therapy" consisting of proton pump inhibitors as omeprazole and the antibiotics clarithromycin and amoxicillin.

  31. Mucosal protective agents. Sucralfate Prostaglandin analogues. Colloidal bismuth

  32. Sucralfate Sucrose octaphosphate + aluminium hydroxide Mechanism of action In acidic pH, sucralfate dissociates into its components. The negatively charged sucrose octaphosphate binds with positively charged protein molecules found in damaged mucosa (Coat over the ulcer). Promote ulcer healing. Inhibition of pepsin.

  33. Stimulation of mucosal protective mechanisms (mucous and bicarbonates secretion). Kinetics Orally, poor systemic absorption. Duration (6 h). Excreted in feces. Avoid co-administration of antacid or H2 blocker. Bette taken on empty stomach.

  34. Therapeutic Uses Benign gastric and duodenal ulcer. Chronic gastritis. Adverse effects Constipation and dry mouth. Interferes with absorption of some drugs tetracycline, theophyline, Tricyclic antidepressant.

  35. 2. Misoprostol Prostaglandin Analogues (PGE1 )  HCL secretion. Promote tight junction of gastric cells prevent back diffusion of HCL.  mucous and bicarbonate secretion. blood flow of mucosa improve healing of ulcer. Kinetics Orally, 30 min. is converted into active metabolite. Excreted in urine- must be taken 3-4 times/day.

  36. Therapeutic uses Prevention of NSAIDS-induced peptic ulcer. Adverse Effects Abdominal cramps (sever colicky pain). Diarrhea. Uterine contraction dysmenorrhea or abortion. Vaginal bleeding.

  37. 3. Colloidal Bismuth compounds Bismuth subcitrate Tripotassium dicitrato bismuthate. Mechanism of Action It forms a precipitate with mucous cover the ulcer with a protective coat that prevent effect of HCl. Promote healing of ulcer. Bactericidal effect against campylobacter pylori . Decrease activity of pepsin  Mucous & bicarbonate secretion.

  38. Adverse Effects Black stool. Teeth discoloration. Encephalopathy (in renal dysfunction). USES Triple therapy for eradication of H. pylori. Benign gastric & duodenal ulcer. Traveller’s diarrhea

  39. Drugs That Neutralize HCL (Antacids) Drugs used to relief gastric pain associated with hypersecretion of HCL. Mechanism of Action • Neutralization of HCL. • Inhibition of pepsin (inactive at PH 5). Therapeutic Uses • relief pain of peptic ulcer. • Dyspepsia.

  40. I - Systemic Antacids Sodium bicarbonate NaHCO3 + HCL  NaCL + CO2. Disadvantages 1. Rebound hyperacidity. • Stomach distension due to CO2 liberation  pain sensation. 3. Sodium load  salt and water retention ( # in cardiac patients). 4. Systemic alkalosis.

  41. Calcium Carbonate CaCO3+HCL  CaCl2 + H2O + CO2 Disadvantages 1. Liberation of CO2  stomach distension 2. 10% is absorbed  hypercalcemia. 3. Rebound hyperacidity. 4. Milk alkali syndrome (hypercalcemia, renal failure).

  42. II – Non Systemic Antacids 1. Aluminum Hydroxide Gel 2. Magnesium Trisilicate Al (OH)3 + HCL  HCL3 + H2O. Advantages • Longer duration of action. • Gradual neutralization of HCL  No rebound hyperacidity. • Adsorbs pepsin. • Minimal change in acid base balance. • No stomach distention

  43. Disadvantages Al (OH)3 • Constipation. • Drug interaction:  absorption of tetracycline, digoxin, iron. Magnesium Trisilicate • Diarrhea • CNS depression (renal failure).

  44. Alginates (Gaviscon) Combine with antacids in reflux esophagitis to increase adherence of mucus to esophageal mucosa.

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