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1 DRUGS USED IN ULCERS AND GIT DISORDERS A peptic ulcer, also known as PUD or peptic ulcer disease is an ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. 80% of ulcers are associated with Helicobacter pylori, a spiral-shaped bacterium that lives in the acidic environment of the stomach. A history of heartburn, gastroesophageal reflux disease (GERD) and use of certain forms of medication can raise the suspicion for peptic ulcer. Medicines associated with peptic ulcer include NSAID (non-steroid anti-inflammatory drugs) that inhibit cyclooxygenase, and most glucocorticoids (e.g. dexamethasone and prednisolone). A gastric ulcer would give epigastric pain during the meal, as gastric acid is secreted, or after the meal, as the alkaline duodenal contents reflux into the stomach. Symptoms of duodenal ulcers would manifest mostly before the meal when acid (production stimulated by hunger) is passed into the duodenum. An esophagogastroduodenoscopy (EGD), a form of endoscopy, also known as a gastroscopy, is carried out on patients in whom a peptic ulcer is suspected. Signs and symptoms are bloating and abdominal fullness, N/V, hematemesis and melena (tarry, foul-smelling feces due to oxidized iron from hemoglobin). The goals of PUD therapy include healing the ulcer and eliminating the cause of the ulcer. Nonpharmacological Treatment: Life style modifications should be continued throughout treatment. Before sleeping: elevate the head of bed to increase esophageal clearance avoid fats, chocolate, alcohol and spearmint avoid spicy foods, orange juice, coffee and excessive tea eat small meals and avoid eating immediately prior sleeping (2 3 hours) lose weight and stop smoking avoid tight fitting clothes Pharmacological Treatment: Antacids and alginic acid: effective in GERD Name Efficacy/Dosage Side Effects Interactions Monitoring/Comments Al(OH) 3 CaCO 3 Only effective for immediate symptomatic relief Not effective for ulcer bleeding or prevention Calcium containing antacid cause rebound acidy and constipation Magnesium containing Decrease bioavailability of digoxin, quniolones, tetracyclines, FQs, Alginate and sodium antacids contain amount of sodium. Alginates form a viscous solution that floats on the surface of the gastric content. Copy right protected Page 1
2 Mg(OH) 2 Na(HCO) 3 30 ml PRN or pc and hs or 2 tabs pc and HS Gaviscon is not a potent acid neutralizing agent. Frequent administration and treatment time is antacids cause diarrhea Aluminum containing antacids cause diarrhea Sodium may be a concern for hypertensive Hypophosphetemia is a concern on long term use of aluminum containing antacids H 2 Receptor Antagonists: block secretion of histamine 2 receptors on parietal cells. Cimetidine (Tegamet) anticholinerigcs and others Separate drugs two hours before or 3 hours after antacids. Magnesium and aluminum antacid are preferred agents. Sodium bicarbonate is contraindicated in HF, severe renal disease, HTN and edema Avoid magnesium containing antacids in renal failure. Alginic acids and aluminum antacids are safe in pregnancy. Higher doses and prolonged Gynecomastia CYP 450 courses are frequently required Impotence inhibitors Effective in mild GERD and gastric ulcer 300 mg BID PO 400 mg OD PO Famotidine (Pepcid) 10, 20 mg tab Nizatidine (Axid) Short-term treatment of active duodenal ulcer, active benign gastric ulcer and GERD up to 4 6 weeks. The most potent agent 20 mg OD BID PO HS Axid is indicated for up to 8 weeks for the treatment of active duodenal ulcer. Axid is indicated for up to 12 weeks for the treatment of endoscopically diagnosed esophagitis Axid is indicated for up to 8 Cimetidine inhibits metabolism of theophylline, warfarin, phenytoin, nifetidine and propranolol Can be used in pregnancy in lower dose Ranitidine should be used cautiously in hepatic impairment Treatment time is 2 8 weeks for all agents despite healing. The plasma half-life of ranitidine is prolonged and total clearance is reduced in the elderly population due to a decrease in renal function. Copy right protected Page 2
3 Ranitidine (Zantec) 75, 150 and 300 mg weeks for the treatment of active benign gastric ulcer. 150 mg OD BID PO The elimination half-life is 3 to 4 hours. The recommended oral dose for the treatment of active duodenal and gastric ulcers is 300 mg/day. 150 mg OD BID PO Proton Pump Inhibitors: block gastric acid secretion by inhibiting H + /K + ATPase in gastric parietal cells. Omeprazole (Losec) Lansoprazole (Prevacid) Pantoprazole (Pantoloc) Rabeprazole (Pariet) Esomeprazole (Nexium) Most effective agents All agents are taken 30 minutes before breakfast in the morning Effective for gastric ulcers, GERD (heart burn) and Zollinger Ellison Syndrome Omeprazole: mg OD PO Pantaprazole: 40 mg/d PO Lansoprazole: 30 mg/d PO Esomperazole: mg/d PO Rabeprazole: mg/d PO Omeprazole is approved in children ages 2 16 years Lansoprazole is approved in children ages 1 11 years Treatment time is 4 8 weeks despite healing Very safe but occasionally cause Dizziness Constipation Not very significant PPIs degraded in acidic environments and are formulated in delayed release caps or tabs. Patients are advised not to chew or crush. Lansoprazole and omeprazole are in granules in capsule and can be mixed in applesauce or placed in orange juice. Pantoprazole is available IV for immediate relief and who can t take oral form If PPIs are dosed twice daily then second dose should be taken 12 hr apart before snack or meal PPIs can be taken concomitantly with antacids. Among PPIs omeprazole is the most potent. Gastric Mucosal Protectant: Copy right protected Page 3
4 Sucralfate PG Analog: It is a nonabsorable aluminum salt of sucrose octasulfate Use for stress ulcer Taken on empty stomach 1 g BID to QID Well tolerated Constipation Antacids bind sucralfate Ketoconazole Warfarin Digoxin Theophylline binds to sucralfate Very limited value is GERD Should be spaced 2 hr apart from other medications Protects ulcerated tissue by forming a barrier or coating Misoprostol (Cytotec) PGE 1 analog Most effective prophylaxis for both gastric and duodenal ulcers Has both antisecreotry and mucosal protective property Given for NSAIDs induced ulcers mcg QID PO with meals Abdominal cramps Absolute contraindicated in pregnancy Motility Agents: Domperidone (Motilium) DA antagonist GIT: Suppress nausea and vomiting 10 mg TID ac & hs Prescribed for the treatment of gastroparesis Lactation: Domperidone, by acting as an antidopaminergic, results in increased prolactin secretion, and thus promotes lactation 10 mg TID QID after breastfeeding Poor CNS penetration Dry mouth MAO Inhibitors Anticholinergics Abdominal cramps Prolactinoma Safe in breastfeeding Obstruction of bowel or perforation Onset of action is in few days Copy right protected Page 4
5 Metoclopramide (Reglan) Tab, injection Prokinectic agent GERD & gastroparesis Chemotherapy induced vomiting Metoclopramide acts on D 2 receptors and in the higher doses enters CTZ in the brainstem, thus blocking nausea/vomiting, enhances the response to ACh to tissues in upper GIT causing enhanced motility, increase gastric emptying and lower esophageal sphincter tone GIT: 5 10 mg TID ac & hs continue for 2 8 weeks PRN Drowsiness Dizziness EPS (Parkinson s symptoms) GI upset Combination therapy to eradicate H. pylori H. pylori is a gram negative bacterium. For diagnosis noninvasive tests (breath test and serology) and invasive test (endoscopy) are used. Drug Combination Dose and Frequency Duration Efficacy Lansoprazole Amoxicillin Clarithromycin 30 mg BID 1 g TID 500 mg BID Esomeprazole Amoxicillin Clarithromycin Bismuth subsalicylate Metronidazole Tetracycline Omeprazole 40 mg qd 1 g BID 500 mg BID 525 mg QID 250 mg QID 500 mg QID 20 mg BID Epilepsy Obstruction or bowel perforation Avoid alcohol Watch dystonic reactions Pheochromocytoma Caution is seizures Avoid with alcohol and CNS agents Copy right protected Page 5
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