Peptic ulcer drugs

overview of peptic ulcer with detailed information on their drugs used in treatment peptic ulcer , pharmacological action, mechanism, uses and adverse effect for both medical and dental students.

1. Peptic ulcer disease By : bibi umeza

2. What is PEPTIC ULCER????? Breaks in mucosal surface > 5mm in size Depth till submucosa In any part of GI tract exposed to aggressive action of acid pepsin juices. Can be acute or chronic Both can penetrate muscularis mucosae..

3. SITES Gastric and duodenal – 98 % Ratio of 1:4 Duodenum:1st part >95% :ant & post walls Gastric : junction b/w antrum &acid secr . mucosa :lesser curvature

4. Why Peptic ulcer occurs ? Imbalance between Aggressive factors and Defensive factors

5. Regulation of gastric acid secretion

6. ETIOLOGY Predisposing factors – Age :young in DU and GU . – Sex :GU commoner in males Causes – H.Pylori – NSAID – Infection: herpes simplex,etc .. – Other drug/toxin: bisphosphonates ,glucocorticoids

7. Pathogenetic factors not related to h.pylori & NSAID Smoking Genetic : blood group O Stress Diet : alcohol and caffeine

8. Associations Systemic mastocytosis Nephrolithiasis Hyperparathyroidism Cirrhosis Alpha antitrypsin deficiency Pancreatitis , polycythaemia vera

9. Pathogenesis Related with NSAIDs Topical NSAIDs .

10. Figure shows machanisms by which NSAIDs may induce mucosal injury :

11. Risk factors for NSAID – induced Gastroduodenal ulcers Established Advanced age. History of ulcer. Concomitant use of glucocorticoids. High dose of NSAIDs. Multiple NSAIDs. Concomitant use of anticoagulants serious or multi system disease. Possible Concomitant infection with H. pylori. smoking . Alcohol consumption.

12. Phathogenesis of H.pylori

13. Types of peptic ulcer Acute peptic ulcer Chronic peptic ulcers - Gastric ulcers - Duodenal ulcer

14. Acute peptic ulcer Ingestion of Aspirin or butazolidin . By stress (Stress ulcer):- May be following endotoxic shock : -Hypotension , -Hemorrhage or -Cardiac infarction

15. Acute peptic ulcer Sepsis. After trauma or neurosurgical operations (Curling’s ulcers). After burns (curling’s ulcers). Patient on steroids The size of peptic ulcer (Steroids ulcers).

16. CHRONIC PEPTIC ULCERS GASTRIC ULCERS . Decrease mucosal resistance. . Pyloroduodenal reflex. . Deficient mucous barriers. . Mucosal trauma. . Local Ischaemia . . Antral stasis. . NSAIDs. . Helicobacter pylori.

17. DUODENAL ULCER Acid hyper secretion. . Genetics factor. . Endocrine organ dysfunction. . Liver abscess. . Emotional factors. . Diet & smoking. . Helicobacter pylori. . Decrease in bicarbonate production.

18. Pathophysiology Gastric ulcer Duodenal ulcer Major causes H.pylori & NSAID H.pylori & NSAID Gastric acid decreased increased Gastric emptying delayed rapid Abnormal resting & stimulated Pyloric sphincter pressure Bicarbonate secretion remarkably decreased

19. Clinical features Abdominal pain* • Epigastric • Burning or discomfort •Awakes from sleep Nausea Weight loss Dyspepsia if not relieved by antacids —penetrating ulcer

20. Treatment ?

21. H2 ANTAGONISTS

22. Mechanism of action Competitively block H2 receptors on parietal cell & inhibit gastric acid production Suppress secretion of acid in all phases but mainly nocturnal acid secretion Also reduce acid secretion stimulated by Ach, gastrin, food, etc.

23. Pharmacokinetics Absorption is not interfered by food Can cross placental barrier and reaches milk, Poor CNS penetration The serum half-lives range from 1.1 to 4 hours; Cleared by a combination of hepatic metabolism, glomerular filtration, and renal tubular secretion. Dose reduction needed in moderate to severe renal insufficiency

24. Comparison of H2 antagonists

25. H2 antagonists - Uses Promote the healing of gastric and duodenal ulcers Duodenal ulcer – 70 to 90% at 8 weeks Gastric Ulcer – 50 to 75% NSAID ulcers induced ulcers Stress ulcer and gastritis GERD Zollinger -Ellison syndrome Prophylaxis of aspiration pneumonia

26. Adverse effects  Headache, dizziness, bowel upset, dry mouth  CNS: Confusion, restlessness  Bolus IV – release histamine – bradycardia , arrhythmia, cardiac arrest  Cimetidine has antiandrogenic actions

27. Proton Pump Inhibitors  Most effective drugs in antiulcer therapy  Prodrugs requiring activation in acid environment  Activated forms binds irreversibly to H+K+ATPase and inhibit it Omeprazole Pantoprazole Lansoprazole Esomeprazole

28. Mechanism of Action  Prodrugs inactive at neutral pH  At pH < 5 rearranges to two charged cationic forms ( sulfenamide + sulphenic acid) that bind covalently with SH groups of H⁺K⁺ ATPase and inactivate it irreversibly  Also inhibits gastric mucosal carbonic anhydrase

29. Pharmacokinetics - PPI  Available as enteric coated tablets  They should be given 30 minutes to 1 hour before food intake  half life is very short and only 1-2 Hrs  Still the action persists for 24 Hrs to 48 hrs after a single dose  Action lasts for 3-4days even after stoppage of the drug

30. Therapeutic uses: 1 . Gastroesophageal reflux disease (GERD) 2 . Peptic Ulcer - Gastric and duodenal ulcers 3 . Bleeding peptic Ulcer 4 . Zollinger Ellison Syndrome 5 . Prevention of recurrence of nonsteroidal antiinflammatory drug (NSAID) - associated gastric ulcers in patients who continue NSAID use. 6 . Reducing the risk of duodenal ulcer recurrence associated with H. pylori infections 7 . Aspiration Pneumonia

31. Adverse Effects  Nausea, loose stools, headache abdominal pain, constipation,  Muscle & joint pain, dizziness, rashes  Rare :  Gynaecomastia , erectile dysfunction  Leucopenia and hepatic dysfunction  Osteoporosis in elderly on prolonged use  Hypergastrinemia

32. Drug interactions  Omeprazole inhibits the metabolism of warfarin, phenytoin, diazepam, and cyclosporine . However, drug interactions are not a problem with the other PPIs.

33. PPI – Dosage schedule  Omeprazole - 20 mg o.d .  Lansoprazole - 30 mg o.d .  Pantoprazole - 40 mg o.d .  Rabeprazole - 20 mg o.d .  Esomeprazole - 20-40 mg o.d

34. Proton Pump Inhibitors  Lansoprazole :  Partly reversible, more potent, slightly more against H.pylori , Higher BA, rapid onset. Pantoprazole:  More acid stable, I.V, CYP450 less affinity Rabeprazole : claimed to most rapid Es -omeprazole  Better intragastric pH , higher healing rates.

35. Antacid - Interactions Absorb drugs and form insoluble complexes that are not absorbed Clinical importance : Interactions can be avoided by taking antacids 2 hrs before or after ingestion of other drugs .

36. Now answer this question Is it rational to combine Aluminium hydroxide and Magnesium hydroxide in antacid preparations ?

37. Systemic antacids • Soluble instant short duration • But cause systemic alkalosis • So other uses – Metabolic acidosis – Alkalinisation of urine – Antipruritic lotion,eye wash,mouth wash

38. Adverse effects constipation , hypophosphatemia • Other uses – Bile reflux Gastritis Stomatitis – Prophylaxis of stress ulcers

39. US FDA Approved Regimen • Lansoprazole 30mg • Amoxicillin 1000mg • Clarithromycin 500mg Twice daily Two weeks

40. Regimen popular in India • Metronidazole 400mg TDS • Amoxicillin 500 mg TDS • Omeprazole 20 mg BD For 1 week

41. Quadruple Therapy Given when Triple Therapy fails CBS - 120 mg qid Omeprazole / Lansoprazole - 20 / 30 mg bd Metronidazole - 400 mg TDS Tetracycline - 500 mg qid

42. Thank You