Peptic Ulcers Notes PDF

& Gastrooesophageal Reflux Disease  K+ H+K+ATP ase H+  Muscarinic antagonists  H2 antagonists  Prostaglandin analogues  Antacids  Proton pump inhibitors 7/1/2024 2 ...

& Gastrooesophageal Reflux Disease  K+ H+K+ATP ase H+  Muscarinic antagonists  H2 antagonists  Prostaglandin analogues  Antacids  Proton pump inhibitors 7/1/2024 2  Superficial Epithelial Cell  PGE2  PGI2  Mucus EP3  EP3  HCO3 Cytoprotection  Sucrafalate, Carbenoxolone 7/1/2024 3 1. Reduction of gastric acid secretion  H2 antihistamines: Cimetidine, Ranitidine, Famotidine, Roxatidine  Proton Pump Inhibitors: Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole, Esomeprazole  Anticholinergics: Pirezepine, Propantheline, Oxyphenonium  Prostaglandin analogue: Misoprostol 7/1/2024 4 2. Neutralization of gastric acid (Antacids)  Systemic: Sodium Bicarbonate, Sod. Citrate  Non Systemic: Magnesium Hydroxide, Mag. Trisilicate, Aluminium Hydroxide Gel, Magaldrate, Calcium Carbonate 3. Ulcer Protectives: Sucralfate, Colloidal Bismuth subcitrate (CBS) 4. Anti-H. Pylori Drugs: Amoxycillin, Clarithromycin, Metronidazole, Tinidazole, Tetracycline 7/1/2024 5  Cimetidine: (Prototype)  All phases: basal, psychic, neurogenic, gastric secretion suppressed  Basal nocturnal secretion suppressed more completely  60-70% reduction of 24hr acid output  Antiulcerogenic effect, ulceration due to stress, drugs is prevented 7/1/2024 6  60-80% bioavailability, first pass hepatic metabolism  Crosses placenta  2/3 excreted unchanged in urine & bile  T1/2: 2-3hrs 7/1/2024 7  Headache, dizziness, bowel upset, dry mouth, rashes  Confused state, restlessness, convulsions & coma  Bolus I.V: Releases histamine resulting in bradycardia, arrhythmia, cardiac arrest  Cimetidine displaces dihydrotestosterone from its cytoplamic receptor, prolactin levels, (-)s degradation of estradiol by liver  Transient rise in aminotransferases 7/1/2024 8  (-)s CYP 450 enzymes  Interactions with: warfarin, phenobarbitone, theophylline, phenytoin  Antacids reduce absorption of H2 blockers  H2 blockers reduce absorption of ketoconazole 7/1/2024 9  5x more potent  Longer duration of action (> 24hrs of suppression)  Little effect outside GIT, less permeability into brain  Does not (-) hepatic metabolism  Overall incidence of adverse effects lower 7/1/2024 10  Longer duration of action  T1/2: 2.5-3.5 hrs  5-8 x more potent than ranitidine  Low affinity for CYP-450  40-50% bioav.  70% excreted in unchanged form  Roxatidine: twice as potent & longer acting than ranitidine 7/1/2024 11  Duodenal ulcers: Rapid & marked pain relief in 2-3 days  60-85% heal at 4 weeks; 70-95% at 8 weeks  About ½ the patients relapse, maintenance therapy with bed time dose reduces relapse rate by 15-20%/year  Gastric ulcers: healing rates somewhat lower ( 50-75% at 8 weeks)  Can heal NSAID associated ulcers  Less effective than PPIs & Misoprost 7/1/2024 12  Acute stressful conditions: Hepatic coma, severe burns, trauma. Prolonged intensive care, asphyxia neonatorum etc: I.V. infusion of H2 blockers prevent gastric lesions & hemorrhage  Zollinger- Ellison Syndrome: Gastrin secreting tumour. H2 blockers in high doses control hyperacidity but relief incomplete. PPI’s drug of choice. Definitive treatment is surgical 7/1/2024 13 GERD: Afford symptomatic relief & facilitate healing of oesophageal erosions by reducing reflux of gastric contents. 2-3 divided doses  Prophylaxis of aspiration pneumonia: Preoperatively 7/1/2024 14  Omeprazole: prototype  (-) final common step in gastric acid secretion  Overtaken H2 blockers for acid-peptic disorders  Dose dependant suppression of gastric acid secretion, no anticholinergic or H2 blocking action  Can totally abolish HCl secretion both resting & stimulated 7/1/2024 15  Active at ph < 5  Inactivates H+K+ATPase enzyme irreversibly  Acid secretion resumes only when new H+K+ATPase molecules are synthesized  Also inhibits gastric mucosal carbonic anyhydrase  P.K.:  Absorption 50%, reduced with food 7/1/2024 16  Best taken empty stomach  Highly plasma protein bound  Rapidly metabolized in liver  No dose adjustment required in elderly or renal/hepatic impairment  Secretion resumes gradually over 3-5 days of stopping the drug 7/1/2024 17 1. Peptic Ulcer:  More effective than H2 blockers  Relief of pain is rapid & excellent  Integral component of anti-H-Pylori therapy  Drug of choice for NSAID induced gastric & duodenal ulcers  Bleeding peptic ulcer: Suppression of acid secretion facilitates clot formation  Stress ulcers: Prophylactic ally as active as H 2 blockers 7/1/2024 18 2. Zollinger Ellison syndrome: More effective than H2 blockers for inoperative cases 3. Aspiration Pneumonia: For prophylaxis  Adverse effects:  Nausea, loose stools, headache, abdominal pain, muscle & joint pain  Infrequently rashes, leucopenia & hepatic dysfn. 7/1/2024 19  (-)soxidation of warfarin, phenytoin, diazepam  Clarithromycin inhibits omeprazole metabolism 7/1/2024 20  Esomeprazole:  Higher bioavailability  Better control of intragastric pH in GERD because of longer t1/2  Lansoprazole:  Higher oral bioavailability, faster onset of action, longer t1/2 7/1/2024 21  Pantoprazole:  Higher oral bioavailability  More acid stable  Particularly for bleeding ulcers & for prophylaxis of acute stress ulcers  Lower affinity for CYP 450: minimal drug interactions  S-Pantoprazole: twice as potent 7/1/2024 22  Rabeprazole:  Fastest acid suppression  Aids in gastric mucin secretion 7/1/2024 23  PGE2 & PGI2: produced in gastric mucosa  (-) acid secretion, promote mucus + HCO3 secretion  (-) gastrin production, mucosal blood flow, ill-defined “cytoprotective” action  Most important is their ability to reinforce mucus layer covering gastric & duodenal mucosa  Misoprostol: in 24 hr acid production less than H2 blockers 7/1/2024 24   Short duration of action ( 4, evoke reflex gastrin release, ‘acid rebound’ occurs esp. in pts. with hyperacidity & duodenal ulcers  Systemic Antacids:  Sodium bicarbonate:  Acts instantaneously but duration of action is short  May raise pH > 7 7/1/2024 27  Al(OH)3 gel  Relaxes smooth muscles, delays gastric emptying  May cause constipation  Binds PO4 in intestine & prevents its absorption: Hypophosphotemia  May result in osteomalacia  Used therapeutically for hyperphosphatemia & phosphate stones 7/1/2024 28  Magaldrate: Hydrated complex of hydroxy magnesium aluminate  Initially rapidly reacts with acid & releases alum. hydroxide  Which reacts slowly  CaCO3  Liberates CO2: Distension, discomfort  Ca2+ ions diffuse into gastric mucosa & HCl production directly by parietal cells, also release of gastrin  Constipation, Ca2+ absorbed in renal insufficiency is dangerous 7/1/2024 29  D.I:  absorption of tetracyclines, iron salts, FQs Ketoconazole  Efficacy of nitrofurantoin reduced by alkalinization of urine  Use:  Only for intercurrent pain relief & acidity  Temporary relief in gastrooesophageal reflux 7/1/2024 30  Sucralfate:  Acts as a physical barrier preventing acid, pepsin & bile from contact  Colloidal Bismuth subcitrate:  Prolonged use: osteodystrophy, encephalopathy (bismuth toxicity)  Blackening of tongue, dentures, stools 7/1/2024 31  Recommended in all tested +ve  All cases of failed therapy & relapse cases of ulcers  Triple therapy x 14 days: PPIs + Clarithromycin 500mg+ (Metronidazole 500mg or amoxycillin 1 g) twice a day  Tetracycline can be subsituted for amoxycillin or metronidazole 7/1/2024 32  Quadruple therapy x 14 days:  PPIs twice a day + Metronidazole 500mg thrice a day+ (bismuth subsalicylate 525 mg + tetracycline 500mg) 4 x daily or  H2-receptor antagonist twice a day + (bismuth subsalicylate 525mg + metronidazole 250mg + tetracycline 500mg) 4x daily 7/1/2024 33  Sporadic uncomplicated heart burn  Less than 2-3 episodes/ week  Not chief complaint  Lifestyle modification, diet, weight loss etc.  Antacids &/or H2-receptor antagonists as needed 7/1/2024 34  Frequent symptoms, with or without oesophagitis  > 2-3 episodes / week  PPIs more effective than H2-receptor antagonists 7/1/2024 35  Chronic, unrelenting symptoms  Immediate relapse off therapy  Esophageal complications: Stricture, Barrett’s metaplasia  PPI either once or twice daily 7/1/2024 36