Anti-ulcer drugs

1. Anti-ulcer drugs Mr. YASAR QAZI Y. B. CHAVAN COLLEGE OF PHARMACY

2. Peptic Ulcer • An Ulcer is … • Erosion in the lining of the stomach or the first part of the small intestine, an area called the duodenum. • Ulcers damage the mucosa of the alimentary tract, which extends through the muscularis mucosa into the sub mucosa or deeper.

3. Ulcers that form in the stomach are called gastric ulcers; in the duodenum, they are called duodenal ulcers. Both types are referred to as peptic ulcers.

4. Peptic Ulcer

5. Pathogenesis of peptic ulcer diseaseimbalance: AGGRESSIVE FACTORS DEFENSIVE FACTORS • Acid • Pepsin • Helicobacter pylori • NSAIDS • Prostaglandins • Mucosal blood flow • Mucous gel layer • HCO3 • Epithelial junctions • Regeneration of the epithelial layer • Epidermal growth factor

6. Helicobacter pylori • 1981 - Robin Warren, M.D., an Australian pathologist, discovered numerous bacteria living in tissue taken during a stomach biopsy. • Spiral urease-producing, Gram-negative bacteria always accompanied changes in the stomach lining

7. Gram negative, Spiral bacilli • Spirochetes • Do not invade cells – only mucous • Breakdown urea - ammonia • Break down mucosal defense • Chronic Superficial inflammation Helicobacter pylori

8. Symptoms of H. pylori • Abdominal pain • Feeling of Fullness • Indigestion • Feeling very hungry 1 to 3 hours after eating • Mild nausea • Pain Starts 2/3 hours after meals, or in the middle of the night

9. Physiology of gastric acid secretion • Gastric acid secretion is a complex, continuous process in which multiple central and peripheral factors contribute to a common endpoint secretion of H⁺ by parietal cells. • Neuronal(acetylcholine,Ach),paracrine(histamine), and endocrine (gastrin) factors all regulate acid secretion. • Their specific receptors (M3,H2,and CCK2 receptors, respectively)are on the basolateral membrane of parietal cells in the body and fundus of the stomach.

10. The H2 receptor is a GPCR that activates the Gs- adenyl cyclase –cyclic AMP-PKA pathway. • Ach and gastrin signal through GPCRs that couple to the Gq-PLC-IP3-Ca2+ pathway in parietal cells . • In parietal cells , the cyclic AMP and the Ca2+ dependant pathways activate H+,K+-ATPase (the proton pump), which exchanges hydrogen and potassium ions across the parietal cell membrane

11. PATHOPHYSIOLOGY

12. symptoms • Burning abdominal pain • Haematemesis • Melena • Nausea or vomiting • Unexplained weight loss • Anorexia • Abdominal fullness

13. diagnosis • Endoscopy: Flexible tube fitted with camera is threaded down the esophagus in to stomach to see the ulcer by physician • Barium meal: Bariumliquid is drunk making ulcer visible on X-ray

14. Test for diagnosing H.pylori • Breath test :by measuring the amount of co2 in exhaled breath. • Blood test: by identifying H.pylori antibodies by ELISA test. • Stool test :stool sample tested with H.pylori antigen.

15. Life-style modification in PUD • Doubtful efficacy • REST • RELAXATION • GOOD SLEEP • DIETINDICATION • Balanced diet • Frequent small meal • fiber • vitamin E and dietary fatty acids • fat diet • CONTRAINDICATION • caffeine-containing beverages • spices • Alcohol

16. ANTI ULCER DRUGS A) REDUCTION OF GASTRIC ACID SECRETION • Histamine antagonist: Cimetidine, ranitidine • Proton pump inhibitors: omeprazole, pantaprazole • Acetyl choline antagonist: pirenzepine, propantheline • Prostaglandin analogue: misoprostol

17. ANTIULCER DRUGS B) Neutralization of gastric acid(antacids) Systemic: Sodium bicarbonate, Sodium citrate Nonsystemic : Magnesium hydroxide , Aluminium hydroxides C) Ulcer protectives : Sucralfate D) Anti helicobacter pylori: amoxicillin, clarithromycin etc

18. Histamine antagonist • Cimetidine • .Histamine antagonists inhibit the action of histamine on the acid-producing cells of the stomach and reduce stomach acid

19. CIMETIDINE SIDE EFFECTS; it include constipation, diarrhea, fatigue, headache, insomnia, muscle pain, and vomiting. Major side effects include confusion and hallucinations, gynacomastia (enlargement of the breasts); impotence. • USES: it is used in treatment of duodenal ulcer, Gastric ulcer, stress ulcer, GERD, zollinger ellison syndrome

20. PROTON PUMP INHIBITORS • Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system of the gastric parietal cells. • The proton pump is the terminal stage in gastric acid secretion

21. PROTON PUMP INHIBITORS OMEPRAZOLE • Omeprazole is inactive at neutral pH, but at pH<5 rearranges to two charged cationic forms(a sulphenic acid and a sulphenamide configurations)that react covalently with SH groups of the H+ K+ ATPase enzyme and inactivate it irreversibly, especially when two molecules of omeprazole react with one molecule of the enzyme • SIDE EFFECTS Stomach pain, Diarrhea,Constipation,Dizziness,Pain,Hives, Itching,seizures

22. ACETYL CHOLINE ANTAGONIST PIRENZEPINE 11-[(4-methylpiperazin-1-yl)acetyl]-5,11- dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin- 6-one • MECHANISM: • It selectively block M1 muscaranic recptors and inhibits gastric secretion. • Because of their relatively poor efficacy, side effects, and risk of blood disorders, they are rarely used today

23. AGENTS THAT ENHANCE MUCOSAL DEFENSE Prostaglandin Analogs: prostaglandins are produced in the gastric mucosa and appear to serve a protective role by inhibiting acid secretion and promoting mucus and bicarbonate secretion. In addition, PGs inhibits gastrin production, increase mucosal blood flow and probably have an ill defined cytoprotective action. DRUGS:Misoprostol

24. MISOPROSTOL MECHANISM: Misoprostol acts upon gastric parietal cells, inhibiting the secretion of gastric acid via G-protein coupled receptor-mediated inhibition of adenylatecyclase, which leads to decreased intracellular cyclic AMP levels and decreased pump activity at the apical surface of the parietal cell • Side effects Diarrhea. Other common side effects include: abdominal pain, nausea, flatulence, headache, dyspepsia, vomiting, and constipation.

25. ULCER PROTECTIVES SUCRALFATE MECHANISM: • Sucralfate is a locally acting substance that in an acidic environment (pH < 4), reacts with hydrochloric acid in the stomach to form a cross-linking, viscous, paste-like material capable of acting as an acid buffer for as long as 6 to 8 hours after a single dose. It also attaches to proteins on the surface of ulcers, such as albumin and fibrinogen, to form stable insoluble complexes. These complexes serve as protective barriers at the ulcer surface, preventing further damage from acid, pepsin, and bile.

26. Side effects The most common side effects seen are constipation. Less commonly reported include flatulence, cephalalgia (headache), xerostomia (dry mouth). • USES: It is used in treatment of Gastritis, Stress ulcers.

27. Sodium bicarbonate (antacid) It is water soluble, acts instantaneously, but duration of action is short. It is a potent neutralizer, pH may raises above 7. Adverse reactions It causes systemic alkalosis, gastric distention, rebound acidity and milk-alkali syndrome Uses It is restricted to casual treatment of heartburn and to treat acidosis

28. ANTI H.PYLORI DRUGS • Anti microbials that have been found clinically effective against H.pylori are: amoxicillin, clarithromycin, tetracycline and metronidazole. • A combination regimen is preferred, using gastric acid inhibitors and antibiotics. Example: • A proton pump inhibitor or H2 blocker + amoxicillin + clarithromycin or metronidazole

29. CONCLUSION

30. Avoid stress • Avoid contamination

31. THANKYOU