Peptic ulcer

Peptic ulcer

1. Peptic ulcer ( Duodenal ulcer + Gastric Ulcer) Peptic ulcer are the open sores that occurs in the lining of the stomach or small intestine. It is the erosion of mucosal layer and break in the lining of the stomach. Peptic ulcer results from imbalance of protective factors (bicarbonate & mucus) and damaging factors (acid & pepsin). Incidence of duodenal ulcer is more common than gastric ulcer. Risk Factors: Smoking Alcohol intake Spicy Food Prolong use of NSAIDS ( e.g : Paracetamol , Ibuprofen, etc) H. Pylori Stress like major injuries, illness, tumor, etc

2. Symptoms Epigastric pain Nausea Vomiting Dyspepsia Bloating B elching Pain after food intake Diagnosis Endoscopy Barium swallow Lab test for H. pylori infection

3. DRUGS FOR PEPTIC ULCER A. Reduction of gastric acid secretion 1. H 2 antihistamines: Cimetidine , Ranitidine, Famotidine 2. Proton Pump Inhibitors (PPI): Pantoprazole , omeprazole , rabeprazole , lansoprazole , esomeprazole 3. Anticholinergics : Pirenzepine , propantheline , oxyphenonium 4. Prostaglandin analogues: Misoprostol , e nprostil , rioprostil B. Antacids 1. Systemic: sodium bicarbonate, sodium citrate 2. Non-systemic: magnesium hydroxide, magnesium trisilicate , aluminium hydroxide, magaldrate , calcium carbonate C. Ulcer proctectives : sucralfate , colloidal bismuth subcitrate D. Anti H. Pylori Drugs : Amoxicillin, Metronidazole , Tetracycline, Clarithromycin

4. Mechanism of Gastric acid secretion

5. H 2 ANTIHISTAMINES MOA : D rugs act on H 2 receptors as antagonist & blocks histamine mediated gastric release. Cimetidine H 2 receptor antagonist Blocks histamine induced gastric secretion Well absorbed orally, bioavailability 60-80% Ranitidine : 5 times more potent than cimetidine Famotidine : 5-8 times more potent than ranitidine & longer duration of action Roxatidine : twice potent & longer acting than ranitidine Nizatidine : high bioavailability

6. Indications Duodenal ulcer Gastric ulcer Stress ulcer & Gastritis Zollinger Ellision Syndrome (ZES): It is a gastric hypersecretory state due to tumor secreting gastrin . Gastroesophageal reflux disease (GERD): It is a recurrent reflex of gastric contents into the esophagus that produces symptoms of heartburn or causes esophageal injury. Prophylaxis of aspiration pneumonia: preanaesthetic medicine before surgery

7. Adverse effects reduced gastric acid production. headache, dizziness, diarrhoea, and muscular pain. confusion and hallucinations occur primarily in elderly patients and after intravenous administration. gynecomastia and galactorrhea (continuous release/discharge of milk). Reduce absorption of drugs such as ketoconazole Contraindications Concurrent use with drugs like metronidazole , phenytion will inhibit their metabolism Coadminstration with drugs like antacids will decrease their absorption

8. PROTON PUMP INHIBITORS (PPI) MOA : Drug inactivates H + K + ATPase enzyme in parietal cells & suppress the secretion of gastric acid. It is very effective inhibition of gastric acid secretion. Omeprazole : Potent & prolong action PPI that irreversibly inhibit H + K + ATPase enzyme & inhibit gastric acid secretion. (Dose: 20-40 mg OD) Pantoprazole : high bioavailability & available as i.v . (Dose: 40 mg OD) Rabeprazole : high Pka , fast suppression of gastric acid secretion (Dose: 20-40 mg OD) Lansoprazole : more potent, higher bioavailability, faster action (Dose: 30 mg OD) Esomeprazole : s- enantiomer of omeprazole , have higher bioavailabilty (Dose: 20-40 mg OD)

9. Indications Peptic ulcer Bleeding peptic ulcer Stress ulcer Zollinger Ellision Syndrome (ZES): It is a gastric hypersecretory state due to tumor secreting gastrin . Gastroesophageal reflux disease (GERD): It is a recurrent reflex of gastric contents into the esophagus that produces symptoms of heartburn or causes esophageal injury. Aspiration pneumonia: preanaesthetic medicine before surgery to avoid aspiration of gastric contents

10. Adverse effects nausea, loose stools, headache, abdominal pain, muscle and joint pain, dizziness are complained by 3–5%. rashes (1.5% incidence), leucopenia & hepatic dysfunction atrophic gastritis, hypergastrinemia on prolonged use. gynaecomastia & erectile dysfunction in some patients accelerated osteoporosis among elderly patients Contraindications PPI inhibits metabolism of diazepam, phenytoin and warfarin . Reduced gastric acidity decreases absorption of ketoconazole and iron salts.

11. ANTICHOLINERGICS Drugs block the muscarinic receptor in parietal cell that cause decreased intracellular ca ++ level & decreases gastric acid secretion. Pirenzepine : selective M1 anticholinergic with fewer side effects (Dose 100-150 mg OD) PROSTAGLANDIN ANALOGUES Drugs stimulate secretion of mucus & bicarbonate ion for protection of stomach lining & inhibit secretion of gastric acid. Misoprostol : longer acting & inhibit acid output dose dependently (Dose 200 µg QID) Contrainication : Pregnancy (may cause abortion)

12. ANTACIDS Drugs that neutralize gastric acid & raise pH of gastric contents . e.g :-magnesium hydroxide, magnesium trisilicate , aluminium hydroxide, magaldrate , calcium carbonate, sodium bicarbonate, sodium citrate Acid Neutralizing Capacity: Number of mEq of 1N HCl that are brought to pH 3.5 in 15 min by unit dose of antacid (1g). Functions of antacids: Neutralization of gastric acidity Inactivate pepsin due to increase pH (>4.0) Reduce peptic activity Reduction of helicobacter pylori Stimulation of PG synthesis

13. NEUTRALIZATION REACTION WITH ANTACIDS

14. Adverse effects Systemic alkalosis Distension, discomfort and belching Sodium overload (edema) Constipation & diarrhoea Contraindications Antacids decrease the absorption of many drugs, especially tetracyclines , iron salts, fluoroquinolones , ketoconazole , H2 blockers, diazepam, phenothiazines , indomethacin , phenytoin , isoniazid , ethambutol and nitrofurantoin .

15. ULCER PROTECTIVES Drugs enhance mucosal protection and prevent mucosal injury, reducing inflammation, and healing existing ulcers. Sucralfate : It binds to proteins of mucosa and forms complex which creates a physical barrier between acid and stomach. It also stimulates prostaglandin release as well as mucus and bicarbonate output, and it inhibits peptic digestion. Since it requires an acidic pH for activation, sucralfate should not be administered with PPIs, H2 antagonists, or antacids. Colloidal Bismuth subsitrate : CBS have anti H. Pylori actions, inhibit the activity of pepsin, increase secretion of mucus, and interact with glycoproteins in mucosal to coat and protect the ulcer.

16. H. pylori is a Gram negative bacteria associated with gastritis, gastric & duodenal ulcers, gastric adenocarcinoma . ANTI H. PYLORI DRUGS Triple therapy (3 drug regimen) for 1 or 2 weeks PPI, Amoxicillin, Clarithromycin , Metronidazole / Tinidazole Quadruple therapy (4 drug regimen) CBS 120 mg QID + Tetracycline 500 mg QID + metronidazole 400 mg TDS + omeprazole 20 mg BD

17. Miscellaneous Drugs Simethicone : antifoaming agent that reduces surface tension, breaks bubble formation and prevents reflux Alginates : Forms a layer of foam on top of gastric contents & reduce reflux Oxethazaine : Surface anaesthetic