Treatment of peptic ulcer
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Treatment of peptic ulcer

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Treatment of peptic ulcer Treatment of peptic ulcer Presentation Transcript

  • ANTACIDS Systemic ANC Sodium bicarbonate- 1-12 mEq HCl sodium citrate- 1- 10 mEq HCl
  • Non-Systemic ANC Magnesium Hydroxide 1- 30 mEq HCl Magnesium trisilicate 1- 10 mEq HCl Aluminium Hydroxide gel 1- 2.5 mEq HCl Magaldrate 1- 28 mEq HCl Calcium carbonate 1- 20 mEq HCl
  • Treatment of Peptic Ulcer
  • ACh PGE 2 Histamine Gastrin Adenyl cyclase ATP cAMP Protein Kinase (Activated) Ca ++ Ca ++ Proton pump K K + H + Gastric acid Parietal cell Lumen of stomach H 2 M PGE receptor Gastrin receptor Proglumide _ + + Antacid Omeprazole _ _ _ _ + + + + + + Misoprostol Ranitidine Pirenzepine _
    • Reversible competitive inhibitors of H 2 receptor
    • Highly selective, No action on H 1 or H 3 receptors
    • Very effective in inhibiting nocturnal acid secretion ( as it depends largely on Histamine )
    • Modest impact on meal stimulated acid secretion (As it depends on gastrin, acetyl choline and histamine)
    Histamine H 2 Receptor Antagonist
  • Bioavailability 80 50 40 >90 Relative Potency 1 5 -10 32 5 -10 Half life (hrs) 1.5 - 2.3 1.6 - 2.4 2.5 - 4 1.1 -1.6 Duration of 6 8 12 8 action (hrs) Inhibition of 1 0.1 0 0 CYP 450 Dose mg(bd) 400 150 20 150 Cimetidine Ranitidine Famotidine Nizatidine
  • H 2 Blockers- Uses 1. Duodenal ulcer 2. Gastric ulcer 3. Stress ulcers and gastritis 4. Zollinger-Ellison syndrome 5. Gastroesophageal reflux disease (GERD)
  • H 2 Blockers–Side effects & Interactions
    • Extremely safe drugs
    • Cimetidine causes gynecomastia, galactorrhea
    • ( as it is antiandrogenic & increases orolactin level )
    • Cimetidine inhibits CYP450 & increases conc. of Warfarin, Theophylline, Phenytoin, Ethanol.
  • Proton Pump Inhibitors (PPIs)
    • Most effective drugs in antiulcer therapy
    • Irreversible inhibitor of H + K + ATPase
    • Prodrugs requiring activation in acid environment
    • Weakly basic drugs & so accumulate in canaliculi of parietal cell
    • Activated in canaliculi & binds covalently to extracellular domain of H + K + ATPase
    • Acid secretion resumes only after synthesis of new molecules
  • Drugs Omeprazole 20 mg o.d. Esomeprazole 20 - 40 mg o.d. Lansoprazole 30 mg o.d. Pantoprazole 40 mg o.d. Rabeprazole 20 mg o.d.
  • Proton Pump Inhibitors – Kinetics
    • Given as enteric coated granules in capsule or enteric coated tablets
    • Pantoprazole also given intravenously
    • Half life – 1.5 hrs
    • Since it requires acid for activation - given 1 hr before meals
    • Other acid suppressing agents not coadministered
  • Uses 1. Gastric ulcer 2. Zollinger-Ellison syndrome 3. Gastroesophageal reflux disease (GERD) Note : drug of choice for NSAID induced gastric/duodenal ulcer
  • P.P.I. – Side effects & Interactions
    • Extremely safe drugs
    • Causes hypergastrinemia which leads to carcinod tumor in rats
    • But no evidence of such tumors in man
    • Inhibit CYP 450 & hence metabolism of warfarin, phenytoin, etc
    • Pantoprazole & Rabeprazole have no significant interactions
  • Prostaglandin Analogues
    • Misoprostil, Enprostil, Rioprostil.
    • Inhibit acid secretion
    • ↑ mucus and HCO 3 - secretion
    • Short duration of action
  • Misoprostol
    • PGE 1 analogue
    • Modest acid inhibition
    • Stimulate mucus & bicarbonate secretion
    • Enhance mucusal blood flow
    • Approved for prevention of NSAID induced ulcer
    • Diarrhoea & cramping abd. pain – 20 %
    • Not so popular as P.P.I are more effective & better tolerated
  • Uses 1. NSAID associated GI disease 2. Patients not responding to H 2 blocker 3. Ulcer Patients who continue to smoke Side effects Diarrhoea Abdominal cramps Abortion
  • Anticholinergics Pirenzipine - M 1 selective Propantheline Oxyphenonium Atropine ↓ volume of gastric juice
  • Mucosal Protective Agents/Ulcer protectives
    • Sucralfate
    • Colloidal Bismuth compounds
  • Sucralfate
    • Salt of sucrose complexed to sulfated aluminium hydroxide
    • In acidic pH polymerises to viscous gel that adheres to ulcer crater
    • Taken on empty stomach 1 hr. before meals
    • Concurrent antacids, H 2 antagonist avoided
    • ( as it needs acid for activation )
  • Colloidal Bismuth Compounds
    • Coats ulcer, stimulates mucus & bicarbonate secretion
    • Direct antimicrobial activity against H.pylori
    • May cause blackening of stools & tongue
    • Not used for long periods – bismuth toxicity
    • Available compounds :
    • Bismuth subsalicylate – in USA
    • Bismuth sobcitrate – in Europe
    • Bismuth dinitrate
  • Ulcer Healing Drugs
    • Carbenoxolone sodium
    • Steroid
    • Derivative of glycyrrhetinic acid
    • Augmentation of mucus production
    • Prolongation of lifespan of gastric epithelial cells
    • Prevention of bile reflux
    • Slowing of PG degradation in gastric mucosa
    • Side effect
    • Mineralocorticoid action
  • Eradication of H.pylori (Anti-H.Pylori Drugs) Triple Therapy Omeprazole / Lansoprazole - 20 / 30 mg bd Clarithromycin - 500 mg bd Amoxycillin / Metronidazole - 1gm / 500 mg bd
    • Given for 14 days followed by P.P.I for 4 – 6 weeks
    • Short regimens for 7 – 10 days not very effective
  • Some other Triple Therapy Regimens are
    • Bismuth subsalicylate – 2 tab qid
    • Metronidazole - 250 mg qid
    • Tetracycline - 500 mg qid
    • Ranitidine Bismuth citrate - 400 mg bd
    • Tetracycline - 500 mg bd
    • Clarithromycin / Metronidazole - 500 mg bd
  • Quadruple Therapy
    • Given when Triple Therapy fails
    • Omeprazole / Lansoprazole - 20 / 30 mg bd
    • Bismuth subsalycilate - 2 tabs qid
    • Metronidazole - 250 mg qid
    • Tetracycline - 500 mg qid
  • Thank You