Drugs that are used for the prevention and treatment ofPeptic Ulcer

Drugs used to treat peptic ulcer

1. Drugs for Peptic Ulcer

2. Peptic ulcer Acid-peptic disease : GERD ( gastroesophageal reflux disease) and Peptic ulcer disease (PUD) It can be duodenal ulcer or gastric ulcer. due to an imbalance between the aggressive factors(acid, pepsin , bile and H. pylori infection, use of NSAIDs) and defensive (gastric mucus and bicarbonate secretion, prostaglandins, nitric oxide, high mucosaI blood flow, innate resistance of the mucosal cells.

3. 6 Regulatory molecules involved in release of HCl : 1)Histamine (secreted by ECL ( Enterochromaffin -like cells); binds with H2-R on parietal cells; Facilitatory ) 2)Acetylcholine (secreted by postganglionic vagal nerves; binds with M3-R on G, ECL and parietal cells; Facilitatory ) 3) Gastrin (secreted by G cells of gastric antrum ; binds with G or CCK2 (CCKB)-R on ECL and parietal cells; Facilitatory )

4. 4)Prostaglandins (PG) : PGE2 and PGI2 (secreted by most cells of gastric mucosa; binds eith EP receptors on parietal cells; Inhibitory) 5) Somatostatin (secreted by D cells of gastric antrum ; binds with SST-receptor on G cells; Inhibitory)

5. The goals of antiulcer therapy are: 1) Relief of pain 2) Healing of ulcer (-usually 4 to 8 weeks continuous drug admin needed; usually hs ) 3)Prevention of complications (bleeding, perforation) 4) Prevention of relapse (most of non-infected cases may need continous (for years) mainatainence daily dose to prevent relapse; relapse minimal if antiinfective agents used)

6. Classification of drugs used in peptic ulcer Antacids: 1)Sodium bicarbonate 2)Sodium citrate 3)Calcium carbonate 4)Magnesium hydroxide 5)Magnesium trisilicate 6) Aluminium hydroxide gel 7) Magaldrate 8)Antacid combinations

7. II ) Prostaglandin analogue: 1) Misoprostol III) H 2 –histaminic receptor antagonists: 1) Cimetidine 2)Ranitidine 3) Nizatidine 4) Famotidine

8. IV) Proton pump inhibitors (PPI): 1) Omeprazole 2) Esomeprazole 3) Lansoprazole 4) Dexlansoprazole 5) Pantoprazole 6) Rabeprazole

9. V) Antimuscarinic agents: 1) Dicyclomine 2) Pirenzepine VI)Mucosal protective agents: 1) Sucralfate 2)Colloidal bismuth subcitrate (CBS)

10. VII) Antimicrobial agents: 1) Clarithromycin 2)Amoxicillin 3) Metronidazole 4)Tetracycline 5) Colloidal b ismuth subcitrate (CBS)

11. ANTACIDS Are weak bases Reacts with HCl to neautralize it and reduce gastric acidity (increase intragastric pH) Increase in pH also inhibits pepsin activity. Usually for symptomatic relief only.

12. Acid neutralizing capacity (ANC): is defined as number of mEq of 1N HCl that are brought to pH 3.5 in 15 min (or 60 min in some tests) by a unit dose of the antacid preparation. (eg 1 g of antacid). 1 N HCl contains 1 Eq (=1000 mEq) ( 6.023x1023 H and the same no. Of Cl atoms) indicates potency of antacids

13. After meal, approx 45 mEq /h of HCl is secreted. A single dose of 156 mEq of an antacid given 1 hour after meal will effectively neutralize HCl for up to 2 hours.

14. a)Sodium bicarbonate (baking soda, NaHCO3) Reacts with HCl instantaneously (very rapid) Water soluble Short duration of action Potent neutralizer of HCl : 1g  12 mEq HCl ; Increases pH upto 7 NaCl and CO2 are formed

15. Uses: 1) only for symptomatic relief of dyspepsia : due to its short duration of axn and requirement of frequent ingestion (every 2 hrs): inconvenient for long-term healing of ulcers. 2) alkalinization of urine 3)treatment of acidosis

16. A/E: 1)Metabolic alkalosis : if high dose of NaHCO3 taken or if pt is having renal insufficiency. due to unreacted NAHCO3 which are systemically absorbed from GIT. 2)Abdominal distention, discomfort, belching 3)increase fluid reetention

17. 4)Acid rebound: raise the antral pH to > 4 evoke reflex gastrin release → more acid is secreted, especially in patients with hyperacidity and duodenal ulcer. occurs for short period only.

18. Interactions: With milk and other dairy products: Excess NAHCO3 + Ca2+ in milk  “Milk alkali syndrome” ( hypercalcaemia , metabolic alkalosis and renal insufficiency)

19. b) Sodium citrate: Properties similar to sod. bicarbonate; 1 g neutralizes 10 mEq HCl ; CO2 is not evolved.

20. c) Calcium carbonate: a potent rapidly acting acid neutralizer (1 g → 20 mEq HCl ), but ANC of commercial preparations is less and variable due to differing particle size and crystal structure.

21. Though it liberates CO2 in the stomach at a slower rate than NaHCO3, it can cause distention and discomfort. The Ca2+ ions are partly absorbed.

22. Ca2+ ions diffuse into the gastric mucosa—increase HCl production directly by parietal cells as well as by releasing gastrin . Acid rebound occurs. Mild constipation or rarely loose motions may be produced. The absorbed calcium can be dangerous in renal insufficiency. Milk alkali syndrome

23. d) Magnesium hydroxide has low water solubility: its aqueous suspension (milk of magnesia) has low concentration of OH¯ ions and thus low alkalinity. However, it reacts with HCl promptly and is an efficacious antacid (1 g → 30 mEq HCl ). Rebound acidity is mild and brief.

24. Osmotic laxative e) Magnesium trisilicate has low solubility and reactivity; 1 g can react with 10 mEq acid, but in clinical use only about 1 mEq is neutralized. About 5% of administered Mg is absorbed systemically—may cause problem if renal function is inadequate.

25. All Mg salts have a laxative action by generating osmotically active MgCl2 in the stomach and through Mg2+ ion induced cholecystokinin release. Soluble Mg salts are used as osmotic purgatives.

26. f) Aluminium hydroxide gel: It is a bland, weak and slowly reacting antacid. On keeping it slowly polymerizes to variable extents into still less reactive forms. Thus, the ANC of a preparation gradually declines on storage.

27. Al3+ ions relax smooth muscle. Thus, it delays gastric emptying. Alum. hydrox . frequently, causes constipation due to its smooth muscle relaxant and mucosal astringent action.

28. Alum. hydrox . binds phosphate in the intestine and prevents its absorption— hypophosphatemia occurs on regular use. This may: (a) cause osteomalacia (b) be used therapeutically in hyperphosphatemia and phosphate stones.

29. Small amount of Al3+ that is absorbed is excreted by kidney. This is impaired in renal failure— aluminium toxicity (encephalopathy, osteoporosis) can occur.

30. have differing ANCs; usually it varies from 1–2.5 mEq /g. Thus, 5 ml of its suspension may neutralize just 1 mEq HCl .

31. f) Magaldrate : It is a hydrated complex of hydroxymagnesium aluminate that initially reacts rapidly with acid and releases alum. hydrox . which then reacts more slowly. The freshly released alum. hydrox . is in the unpolymerized more reactive form. Thus, magaldrate cannot be equated to a physical mixture of mag. and alum. hydroxides.

32. . It is a good antacid with prompt and sustained neutralizing action. Its ANC is estimated to be 28 mEq HCl /g

33. Antacid combinations: A combination of two or more antacids is frequently used

34. (a) Fast (Mag. hydrox .) and slow (Alum. hydrox .) acting components yield prompt as well as sustained effect. (b) Mag. salts are laxative, while alum. salts are constipating: combination may annul each other’s action and bowel movement may be least affected. (c) Gastric e

35. Other additives: 1) alginate : increases adherence on mucosal surface e.g. Of lower esophagus  protects the surface 2) simethicone: Antifoaming agent ; Prevents flatulance.

36. Interactions: tetracyclines , iron salts, fluoroquino lones , ketoconazole , H2 blockers, diazepam, phe nothiazines , indomethacin , phenytoin , isoniazid , ethambutol and nitrofurantoin : By raising gastric pH and by forming complexes, the non-absorbable antacids decrease the absorption of many drugs, especially. given after 2 hours.

37. 2) Nitrofurantoin : The efficacy of nitrofurantoin is also reduced by alkalinization of urine. 3)With dairy products: Milk-alkalosis syndrome with NAHCO3 and CaCO3.

38. S/P 1) Some antacids formulations contain high Na content  can worsen CHP.

39. Misoprostol Synthetic analogue of PG E1 Is methylPGE1 ester is a longer acting possess “ cytoprotective ” effects on gastroduodenal mucosa.

40. MOA: 1) inhibits release of H+: by binding with PGE receptor located on basolateral membrane of parietal cell (↓ cAMP ) 2) stimulates release of mucin and bicarbonate by mucosal cells 3) inhibit gastrin release 3) increase mucosal blood flow by causing vasodilation .

41. shorter duration of action (~3 hr) when compared to H2-antagonists – requires multiple daily doses.

42. Uses: 1) Peptic ulcer : esp those caused buy NSAIDs (since NSAID ↓ PG synthesis  increases risk of bleeding and ulcers) PPIs are preferred as they more effective, more convenient, better tolerated and cheaper.

43. A/E: 1) misoprostol is poorer in relieving ulcer pain. Some patients may even complain of increased pain during the first week of therapy. 2) Nausea, diarrhoea , abdominal cramps 3) uterine bleeding C/I: 1) in pregnancy : contraction of uterus  termination of pregnancy

44. H 2 receptor antagonists (H 2 antihistamines Introduction: These are the first class of highly effective drugs for acid-peptic disease, but have been surpassed by proton pump inhibitors (PPIs). These act selectively on H2 histamine receptors. Histamine is implicated in secretion of H+ from parietal cells.

45. Includes drugs like Cimetidine , Ranitidine Nizatidine Famotidine Roxatidine

46. Cimetidine : first H2 blocker to be introduced clinically ; prototype, though other H2 blockers are more commonly used now; hydrophilic; low potency (800mg od hs ); greater interactions; sexual A/E Ranitidine: moderate potency Nizatidine : moderate potency Famotidine : High potency

47. Pharmacological Effects ( Cimetidine as prototype) are highly selective: have no effect on H1 mediated responses. blocks histamine-induced gastric secretion and cardiac stimulation (at high doses). the basal nocturnal acid secretion is suppressed more effectively.

48. The volume of gastric juice, pepsin content and intrinsic factor secretion are reduced, but the most marked effect is on acid. However, normal vit B12 absorption is not interfered. The usual ulcer healing doses produce 60–70% inhibition of 24 hr acid output.

49. Mechanism of action Gastric acid secretion is stimulated by acetylcholine, histamine, and gastrin. The receptor-mediated binding of acetylcholine, histamine, or gastrin results in the activation of protein kinases, which in turn stimulates the H+/K+-adenosine triphosphatase (ATPase) proton pump to secrete hydrogen ions in exchange for K+ into the lumen of the stomach. By competitively blocking the binding of histamine to H2 receptors, these agents reduce the secretion of gastric acid.

50. competitive antagonist for H2-receptor present on basolateral surface of gastric parietal cells.

51. Pharmacokinetics Available dosage forms: both oral and parenteral . adequately absorbed bioavailability is 60–80% due to first pass hepatic metabolism. Absorption is not interfered by presence of food in stomach.

52. crosses placenta and reaches milk, but penetration in brain is poor because of its hydrophilic nature. M&E: 2/3 of a dose is excreted unchanged in urine and bile, the rest as oxidized metabolites. The elimination t½ is 2–3 hr.

53. Indications 1 ) Duodenal ulcer 2) Gastric ulcer 3) Stress ulcers and acute gastritis 4) Zollinger -Ellison syndrome 5) Gastroesophageal reflux disease ( GERD) 6) Nonulcerative dyspepsia 7 ) Prophylaxis of aspiration pneumonia 8 ) Others

54. Duodenal ulcer: rapid and marked pain relief (within 2–3 days). Ulcers heal at 4 to 8 weeks continuosly , but relapse within 1 year of healing, hence maintenance therapy with bed time dose needed as long as required.

55. 2) Gastric ulcer Lower healing rates (when compared to duodenal ulcers). less effective than PPIs or misoprostol in NSAID associated ulcers.

56. 3) Stress ulcers and gastritis As a prophylaxis against acute stress ulcers: in patients undergoing prolonged surgery or prolonged intensive care. Where mucosal ischaemia along with acid is causative. -intravenous infusion given.

57. 4) Zollinger -Ellison syndrome: It is a gastric hypersecretory state due to a rare tumour secreting gastrin . However PPIs are the drugs of choice. Definitive treatment is surgical.

58. 5) Gastroesophageal reflux disease (GERD): indicated only in mild cases of GERD. afford symptomatic relief and facilitate healing of esophageal erosions, but are less effective than PPIs.

59. 6) Prophylaxis of aspiration pneumonia Can be used as a preanaesthetic medication. given preoperatively (preferably evening before surgery) reduce the risk of aspiration of acidic gastric contents during anaesthesia and surgery.

60. 7) Other uses: as an adjuvant drug in certain cases of urticaria which do not respond adequately to an H1 antagonist alone.

61. Interactions 1) Cimetidine inhibits several cytochrome P-450 isoenzymes theophylline , phenytoin , carbamazepine , phenobarbitone , sulfonylureas , metronidazole , warfarin , imipramine , lidocaine , nifedipine , quinidine  raised Cp

62. 2) Antacids reduce absorption of all H2 blockers. When used concurrently a gap of 2 hr should be allowed. 3) Ketoconazole absorption is decreased by H2 blockers due to reduced gastric acidity.

63. A/E well tolerated. Headache, dizziness, bowel upset, dry mouth, rashes. Transient elevation of plasma aminotransferases ; but hepatotoxicity is rare

64. 3) Cimetidine (but not other H2 blockers) has antiandrogenic action (displaces dihydrotestosterone from its cytoplasmic receptor), increases plasma prolactin and inhibits degradation of estradiol by liver. High doses given for long periods have produced gynaecomastia , loss of libido, impotence and temporary decrease in sperm count, galactorrhoea in females.

65. 4) CNS (confusion, delirium, hallucinations, slurred speech, and headaches), which occur primarily at high doses with intravenous administration of the drugs or in elderly subjects.

66. S/P Dose reduction is needed in renal insufficiencies.

67. Ranitidine: a non- imidazole (has a furan ring in place of imidazole ring) preferred over cimetidine because: i ) higher potency (300mg qd hs ): About 5 times more potent than cimetidine . A longer duration of action with greater 24 hr acid suppression is obtained clinically because of higher potency.

68. ii)no adverse effects on male and female sexual functions. iii) Lesser permeability into the brain: lower propensity to cause CNS effects. iv) Less marked inhibition of hepatic metabolism of other drugs: lesser clinically significant drug interactions v) Overall incidence of side effects is lower

69. b) Famotidine Contains thiazole ring. Highly potent (40mg qd hs )(binds tightly to H2 receptors) and exhibits longer duration of action. Antiandrogenic action is absent. Minimal CYP inhibition: least interactions excreted by the kidney, 70% in the unchanged form.

70. c) Roxatidine : roxatidine is similar to that of ranitidine, but it is twice as potent and longer acting. It has no antiandrogenic or cytochrome P450 inhibitory action

71. ANTICHOLINERGICS Atropinic drugs reduce the volume of gastric juice without raising its pH unless there is food in stomach to dilute the secreted acid. Stimulated gastric secretion is less completely inhibited. Effective doses (for ulcer healing) of nonselective antimuscarinic drugs (atropine, propantheline , oxyphenonium ) always produce intolerable side effects- hence not preferred.

72. Pirenzepine : It is a selective M1 anticholinergic . Gastric secretion is reduced by upto 50% without producing intolerable side effects, but side effects do occur with slight excess dose.

73. Mucus protective agents Sucralfate Colloidal bismuth subcitrate (CBS)

74. Sucralfate : is a basic aluminium salt of sulfated sucrose. Its action is entirely local. pharmacokinetics: Oral; minimally absorbed delays gastric emptying—its own stay in stomach is prolonged.

75. Mechanism of action: Sucralfate polymerizes at pH < 4 by cross linking of molecules, assuming a sticky gel-like consistency. It preferentially and strongly adheres to ulcer base, especially duodenal ulcer (for upto 6 hours).

76. Surface proteins at ulcer base are precipitated, together with which it acts as a physical barrier preventing acid, pepsin and bile from coming in contact with the ulcer base. Dietary proteins get deposited on this coat, forming another layer.

77. Uses: Gastric and duodenal ulcers: promotes healing of both duodenal and gastric ulcers. Healing efficacy has been found similar to cimetidine . The ulcer healing dose of sucralfate is 1 g taken in empty stomach 1 hour before the 3 major meals and at bed time for 4–8 weeks ( qid , hence inconvenient)

78. 2)Bile reflux 3)Gastritis 4) prophylaxis of stress ulcers: Intragastric sucralfate provides effective prophylaxis of stress ulcers without acid suppression, and is an alternative to i.v . H2 blocker or PPI.

79. 5) stomatitis : Used as a topical suspension (with glycerol) 6) On burns, bedsores, diabetic/ radiation ulcers, excoriated skin, etc: as topical protective agent.

80. A/E: Hypophosphatemia – due to its binding with phosphate ions in the intestine. Constipation, dry mouth and nausea. If used with i.v . or intragastric H2 blocker or PPI (i.e. drugs which ↓ acidity), risk of pneumonia due to overgrowth of bacteria in the stomach. ‘bezoar’ (hard mass of entangled material in stomach) formation

81. Interactions: Antacids should not be taken with sucralfate because its polymerization is dependent on acidic pH  reduces its efficacy Sucralfate adsorbs many drugs and interferes with the absorption of tetracyclines , fluoroquinolones , cimetidine , phenytoin and digoxin .

82. S/P In renal insufficiencies: since Al may get absorbed and are excreted via kidney  long term use may lead to Al toxicity.

83. Colloidal bismuth subcitrate Aka CBS or Tripotassium dicitratobismuthate . is a colloidal bismuth compound water soluble but precipitates at pH < 5. Pharmacokinetics: Most of the ingested CBS passes in the faeces . Small amounts absorbed are excreted in urine.

84. Mechanism of action: Probable mos include: i ) increase gastric mucosal PGE2, mucus and HCO3 ¯ production. ii) precipitation of mucus glycoproteins and cause coating of the ulcer base. iii) May detach and inhibit H.pylori directly.

85. Uses: Gastric and duodenal ulcers: heals ulcers when given for 4 to 8 weeks. 120 mg (as Bi 2 O 3 ) taken ½ hr before 3 major meals and at bedtime for 4–8 weeks. Can be used as a component of MDT regimen for H. pylori infected cases. 2) traveller’s diarrhoea: since it binds enterotoxin .

86. Interactions: 1) Milk and antacids should not be taken concomitantly. A/E: 1) diarrhoea , headache and dizziness 2) blackening of tongue, dentures and stools

87. Proton-pump inhibitors ( PPls )

88. These are the drugs which show its therapeutic action by preventing the secretion of H+ ions into the gastric lumen. PPI includes drugs like: Omeprazole Esomeprazole Pantoprazole Lansoprazole Dexlansoprazole Rabeprazole Dexrabeprazole llaprazole

89. Omeprazole: racemic mixture Prodrugs, Acid labile Lipophilic Weak bases (pKa 3.9 to 5) ; (O,E,L,D- pKa 4; P- 3.9; R- 5)

90. Omeprazole the prototype member of substituted benzimidazoles . It is a powerful inhibitor of gastric acid, which can totally abolish HCI secretion, both resting as well as that stimulated by food or any of the secretagogues .

91. Pharmacokinetics Available in oral dosage form as i ) enteric coated ( e.c .) tablets or capsules, or ii) with NaHCO3 : as immediate release powder to form suspension. to protect them from molecular transformation in the acidic gastric juice. E, P : in i.v. form

92. Oral bioavailability ~ 50% (Rapid first pass hepatic metabolism) They should be taken in empty stomach (about 1 hr before meal ) 1) F decreases with food. 2) Empty stomach : only 10 % PP active; At the time ppi reaches Cmax (around 1 h), most of pp have been acivated (due to the meal ).

93. highly plasma protein bound rapidly metabolised in liver by CYP2C19 and CYP3A4. It also inhibits CYP2C19 . Plasma t½ of all PPI ~ I to 2 hr but prolonged (24 h) duration of action (due to irreversible binding; hence qd) The metabolites are excreted in urine.

94. Mechanism of action At pH < 5, it gets concentrated in the acidic canaliculi (due to pKa 4 to 5) because the charged forms generated at the acidic pH are unable to diffuse back. it rearranges to two charged cationic forms that react covalently with SH groups of the H + K + ATPase enzyme (the proton pump) and inactivate it irreversibly . Hence, H+ fails to be transported into the gut lumen, leading to decrease formation of HCl and reduced acidity. It also acts by inhibiting carbonic anhydrase enzyme.

95. In canaculi , prodrug  to a reactive thiophilic sulfenamide cation , which forms irreversible covalent disulfide bond with proton pump.

96. Interactions 1) diazepam, phenytoin and warfarin levels may be increased : due to decreased metabolism. 2) Clopidogrel (a prodrug ): efficacy decreased due to decreased activation. (CYP2C19 inhibition; P,R- least interaction)

97. 3) Itraconazole, ketoconazole and iron salts: decreased absorption due to reduced gastric acidity. 4) Clarithromycin: increases plasma concentration of omeprazole.

98. Dose Oral: 20 to 40 mg tab/ Capsules (containing enteric-coated granules) Parenteral : E, P

99. Indications/ Uses Peptic ulcer: more effective in healing ulcers (duodenal and gastric ulcers) than ranitidine. PPls are an integral component of anti-H. pylori therapy. For NSAID induced gastric/duodenal ulcers: Higher dose or twice daily treatment given for longer periods.

100. 2) Bleeding peptic ulcer: which occurs esp. after therapeutic endoscopy. By reducing acid secretion, promotes clot formation and healing. 3) In stress ulcers: in patients undergoing prolonged surgery or prolonged intensive care.

101. 4) Gastroesophageal reflux disease (GERD): are the drugs of choice. Higher doses or twice daily dosing is generally needed. 5) Nonulcer dyspepsia

102. 5) Zollinger -Ellison syndrome: is a gastric hypersecretory state due to ' gastrinoma ', a rare tumour secreting gastrin . higher doses needed (O 60-120 mg/day) 6) Prophylaxis of aspiration pneumonia: during prolonged anaesthesia .

103. Adverse effects diarrhoea, headache, and abdominal pain. Risk of acute interstitial nephritis and chronic kidney disease with prolonged use. Risk of dementia – with prolonged use Osteoporosis and increased risk of bone fractures (due to reduced absorption of food-bound Ca2+). Severe hypomagnesemia with secondary hypocalcemia – due to decreased gi absorption.

104. 6) Infections like pneumonia and enteric infections like Clostridium difficile. 7) Atrophic gastritis and benign polyps 7) Rebound acid hypersecretion : on discontinuation the drug. Seen as dyspepsia (feeling of hyperacidity and indigestion) or heartburn. Reversible. due to increased gastrin level.

105. Drugs used in the eradication of Helicobacter pylori (H. pylori)

106. H. pylori is a gram negative bacillus uniquely adapted to survival in the highly acidic environment of stomach. important contributing factor to the causation of chronic gastritis, dyspepsia, peptic ulcer, gastric lymphoma and gastric carcinoma Up to 90% patients of duodenal and gastric ulcer have tested positive for H. pylori

107. Antimicrobials that can be used for the eradication of H. pylori infection include: 1) Amoxicillin 2) Clarithromycin 3) Tetracycline 4) Metronidazole 5) Tinidazole 6) Colloidal bismuth subcitrate (CBS).

108. 2 or more anti-Helicobacter pylori antibiotic drugs are used in combination with PPI:

109. Treatment regimens: A)Triple drug regimen: mostly used. It involves simultaneous administration of 3 drugs for 1 to 2 weeks, of which, One is a PPI and other two are antibiotics. a) Omeprazole 40 mg OD + Metronidazole 400 mg TDS + Amoxicillin 500 mg TDS

110. b) In areas of higher prevalence of metronidazole resistance: Lansoprazole 30 mg + Amoxicillin I000 mg + Clarithromycin 500 mg, (all given twice daily for 2 weeks)

111. B) Quadruple drug regimen: In cases of Clarithromycin -resistance: One PPI + two antibiotics + CBS CBS 120 mg QID + tetracycline 500 mg QID + metronidazole 400 mg TDS + omeprazole 20 mg BD (for 1 to 2 weeks)

112. For large ulcers (> 10 mm in diameter) or those complicated by bleeding/perforation, the PPI should be continued beyond the 2 weeks-triple drug regimen till complete healing occurs

113. Rationale of MDT 1) prevention of resistance: Use of 2 or more antimicrobials prevent the development of antimicrobial resistance. Any single antibiotic is ineffective. Resistance develops rapidly, especially to metronidazole / tinidazole and clarithromycin , but amoxicillin resistance is infrequent.

114. 2)bismuth (CBS) is active against H. pylori and resistance does not develop to it, combination regimens including bismuth may be used in case of metronidazole and clarithromycin double resistance.

115. 2)Acid suppression by PPIs/H2 blockers enhances effectiveness of anti-H. pylori antibiotics : increased pH decreases MIC of antibiotics against H pylori.

116. 3)PPIs benefit by altering the acid environment for H. pylori as well as by direct inhibitory effect. 4) Fa ster ulcer healing 5) Minimizes relapse .

117. Common a/e with H. Pylori eradication therapy: 1) diarrhoea Usually mild, But Clostridium difficile associated colitis can occur. 2) Flushing and vomiting (metronidazole + ethanol) 3) Nausea and vomiting 4) Abdominal cramp 5) Headache 6) rash

118. THANK YOU

119. Home assignments List of 20 orally administrable drugs whose absorption is retarded at higher pH of git. Reason for such effect.