GI Drugs Flashcards
When we talk about ulcers, what is the overlying pathophysiology? What induces acid production? In treating ulcers, what are the three goals we have? What are the four criteria by which we judge treatment? Outline the strategies we use to accomplish each treatment goal.
Ulcers: 1 - Too much acid, 2 - Loss of mucosal protection. Acid: Gastrin (chief cells in the antrum), Acetylcholine (vagus), Histamine (stimulated by Ach & gastrin), Parietal cell H/K ATPase (final common pathway). Three treatment goals: Neutralize acid, Decrease acid production, Increase mucosal resistance. Rating treatment: Relief of symptoms (pain!), Promotion of healing, Prevention of complications (perforation, hemorrhage, scar), Prevention of recurrence.
1 - Neutralize acid:
__Antacid therapy: Relieves pain & achieves ulcer healing, but requires extremely high doses to do so, and probably does not treat or prevent relapse. Have been relegated to a “use as needed” basis in addition to therapy.
__Decrease acid production: Anticholinergic agents, H2 blockers, H/K ATPase inhibitors.
__Improve mucosal resistance: Mechanical protectors, Prostaglandin E2 analog, Eradication of H. pylori via combination therapy.
Anticholinergics used in GI? MOA? Use? Side effects? Contraindications?
Atropine sulfate, Propantheline, Metantheline bromide. MOA: Reduce acid secretion & reduce spasm. Use: Ulcer treatment (for propantheline &metantheline take 15-30 minutes before meals and before bed). Side effects: Anticholinergic. Contraindications: known pyloric obstruction, hiatal hernia, or peptic esophagitis (not used much).
Histamine H2 blockers? MOA? Use? Side effect? Which interfere with P450? Is one dose as effective as multiple?
Cimetidine, Ranitidine, Nizatidine, Famotidine. MOA: Inhibit 50-80% of 24 hour acid production. Use: Ulcer treatment (first class to satisfy all 4 requirements); prophylactically for stress ulcers; GERD. Side effect: Rebound acidity if stopped suddenly, Uncommon: headache, lethargy, confusion, depression, and hallucination. P450 interference: Cimetidine, Ranitidine. One dose is as effective as multiple.
Prostaglandin E analog? Use? Side effects? Is this effective?
Misoprostol. MOA: Decrease acid production, increase mucous and bicarbonate secretion. Use: Ulcer treatment when prostaglandin production decreased – thus, this is the ONLY FDA-approved drug for the prevention of NSAID-induced gastric ulcers!! – Not very effective elsewise because endogenous prostaglandin levels are already high in duodenal ulcer patients.
H/K ATPase inhibitors? MOA? Uses? Which can be used best for H. pylori? Side effects? Which interferes with P450 the most? Which have “some” interference? Which has no interference? Which has lowest bioavailability? Which has greatest bioavailability?
Omeprazole, Lansoprazole, Rabeprazole, Pantoprazole, Esomeprazole. MOA: Inhibit >90% of 24 hour acid secretion (better than H2 antagonists); requires acid
environment to activate (don’t take with antacids). Use: Ulcer, GERD. For H. pylori: Omeprazole, Lansoprazole. Side effects: Headache, gynecomastia, gastric hyperplasia in humans and carcinoid tumors in rats long
term (do not use long-term). Omeprazole has the greatest P450 interferenc, Lansoprazole & Esomeprazole have “some” P450 interference. Rabeprazole has moderate P450 interference. Pantoprazole has no P450 interference. Omeprazole has lowest bioavailablity. Lansoprazole has greatest bioavailability.
Mechanical protectors? MOA? Side effects? Which turns bowel movements and tongue black?
Sucralfate, Bismuth salts. MOA: Increase mucosal resistance by coating the ulcer crater. MOA: Mostly used as an adjunct in ulcer treatment, treatment for H. pylori. Aluminum toxicity possible in renal failure. Black: bismuth salts.
Ok, so what about eradicating H. pylori? What drugs and combinations of drugs do we use? Are the combinations different in terms of efficacy?
Bismuth salts & antibiotics. “TRITEC” triple therapy = PPI or ranitidine bismuth citrate + 2 antibiotics (amoxicillin, clarithromycin, metronidazole). Quadruple therapy: PPI + Tetracycline + Metronidazole + Bismuth subsalicylate or subcitrate. There probably is no difference between the two therapies, unless resistant H. pylori is preseent, in which case the triple therapies may be better.
Antacids? Used for? Side effects? Which can be used in renal failure? Which should be avoided in renal failure?
Calcium carbonate (Milk-alkali syndrome,
nephrocalcinosis, “rebound” acidity,
digitalis antagonism, constipating), Sodium bicarbonate (systemic alkalosis, enhanced effects of
amphetamine, quinidine, and
cinchophen), Magnesium hydroxide/Magnesium carbonate (diarrhea – laxative effect, Hypokalemia,
hypermagnesemia, iron deficiency), Aluminum hydroxide (Phosphate depletion and sequelae – weakness, anemia, tetany, apnea; constipation). Ulcer treatment & GERD. Aluminum hydroxide is safe for use in renal failure (and helps eliminate phosphate). Magnesium drugs cannot be used in renal failure.
In GERD, what two pathophysiological variables play a role? Outline the treatment strategies we use.
1 - LES inappropriate relaxation + Low resting tone + Anatomical alterations, 2 - Acid hypersecretion. Treatment:
Lifestyle
W/O Esophagitis: Alginc acid antacids, Promotility drugs, H2 Blockers. (and/or)
W/ Esophagitis: H2 bockers (possibly @ an increased dose), H2 blocker + Promotility agent, PPI, Antirefluz surgery. (or)
Promotility agents? MOA? Which can also be used as an anti-emetic? All can be used for ____, but __ & __ can also be used for ____. Side effects?
Metochlopramide, Cisapride, Domeperidone. M & C are dopamine antagonists. MOA: M - Increase motor tone in lower esophageal sphincter (prevent reflux) and stomch (esp. antrum: improves gastric emptying); peripheral (stomach) and CNS (vomiting, via CRTZ) dopamine antagonist, C - Increase motor tone in lower esophageal
sphincter and stomch, D - Improves gastric tone. All for gastroparesis, M & C also for GERD. Side effects: M - Hand tremor if used 4X/day (optimum use); possible extrapyramidal symptoms, but not so severe, C - Sudden cardiac death.
Anti-emetics? Which are the phenothiazines (nueroleptics)? Which is the benzamide derivative? Which are seretonin (5HT3) receptor antagonists? Give MOA. Side effects? Which is safest in young children?
Prochlorperazine Promethazine Trimethobenzamide Tetrahydrocannabino Ondansetron Granesitron Dolasetron. Phenothiazines: Prochlorperazine & Promethazine. Benzamide derivative: Trimethobenzamide. 5HT3 antagonists, Ondansetron, Gransitron, Dolasetron. Phenothiazines: Probable CNS interaction with dopaminergic receptor-antagonist (leading to reduction of stimulation in the CRTZ in the medulla) + Antihistaminic (H1 receptor), anticholinergic. Benzamide: Unknown effect on CRTZ. THC: Suppress CRTZ via anticholinergic properties. 5HT3 blocks: Block CRTZ. Prochl: Largely extra-pyramidal (torticollis!). Prometh: Somnolence (especially in the
elderly). THC: Munchies. Trimeth: Low-side effect profile; possible extra-pyramidal symptoms, but not so severe. 5HT3 blocks: Headache, dizziness, somnolence. Young children: Ondansetron.
Opioids used for diarrhea? MOA? Which are contraindicated in children? Which is used in combo with atropine?
Loperamide, Codeine, Diphenoxylate. MOA: Less penetration to CNS; stimulates μ receptors in GI tract; increased rectal tone leading to segmentation of colon and disruption of peristalsis, leading to increased absorption time. Contraindication: children (narcotic
will cause respiratory suppression). Lomotil = diphenoxylate + atropine.
Anti-cholinergic used to treat diarrhea?
Atropine sulfate – Anti-cholinergic –
Relax all bowel smooth muscle (because
most innervation of the bowel is cholinergic).
Drugs that treat diarrhea by absorbing water? Will these drugs prevent from dehydration?
Metamucil (Colloid) & Bismuth subsalicylate (Pectin). Will not prevent from dehydration.
Irritant/stimulants used to treat constipation?
Castor oil; Cascara sagrada; senna extract; Bisacodyl;
phenolphthalein – Irritate lumen of the colon, causes peristaltic contractions.
