Drugs used in acid-peptic diseases |
Proton pump inhibitors (PPIs; eg, omeprazole) Irreversible blockade of | H+/ K+ ATPase in active gastric parietal cells | Peptic ulcer, GERD, erosive gastritis | Half-lives much shorter than duration of action | Low toxicity • reduction of stomach acid may reduce absorption of some drugs and increase that of others |
Other PPIs: esomeprazole, dexlansoprazole, lansoprazole, pantoprazole, rabeprazole H2-receptor blockers: cimetidine, famotidine, nizatidine, ranitidine reduce nocturnal acid but less effective than PPIs against stimulated secretion; very safe, available over the counter (OTC). Cimetidine, but not other H2blockers, is a weak antiandrogenic agent and a potent CYP enzyme inhibitor Sucralfate: polymerizes at site of tissue damage and protects against further damage; very insoluble with no systemic effects; must be given 4 times daily Antacids: popular OTC medication for symptomatic relief of heartburn; not as useful as PPIs and H2blockers in peptic diseases |
Prokinetic agents |
Metoclopramide | D2receptor blocker • increases gastric emptying and intestinal motility | Gastric paresis (eg, in diabetes) • antiemetic | Oral and parenteral formulations | Parkinsonian symptoms due to block of CNS D2receptors |
Domperidone: like metoclopramide but less CNS effect; not available in United States Cholinomimetics: neostigmine used for colonic pseudo-obstruction in hospitalized patients Macrolides: erythromycin useful in diabetic gastroparesis but tolerance develops |
Laxatives |
Magnesium hydroxide, other nonabsorbable salts and sugars | Osmotic agents increase water content of stool | Simple constipations • bowel prep for endoscopy (especially PEG solutions) | Oral | Magnesium may be absorbed and cause toxicity in renal impairment |
Bulk-forming: methylcellulose, psyllium, etc; increase volume, stimulate evacuation Stool surfactants: docusate, mineral oil; lubricate stool, ease passage Stimulants: senna, cascara; stimulate activity; may cause cramping Chloride channel activator: lubiprostone, prostanoic acid derivative, stimulates chloride secretion into intestine, increasing fluid content Opioid receptor antagonists: alvimopan, methylnaltrexone, block intestinal μ opioid receptors but do not enter CNS, so analgesia is maintained |
Antidiarrheal drugs |
Loperamide | Activates μ opioid receptors in enteric nervous system and slows motility with negligible CNS effects | Nonspecific, noninfectious diarrhea | Oral | Mild cramping but little or no CNS toxicity |
Diphenoxylate: similar to loperamide, but high doses can cause CNS opioid effects and toxicity Colloidal bismuth compounds: subsalicylate and citrate salts available as OTC products; have some value in travelers' diarrhea due to absorption of toxins Kaolin + pectin: adsorbent compounds available OTC |
Drugs for irritable bowel syndrome (IBS) |
Alosetron | 5-HT3receptor antagonist of high potency and duration of binding • reduces smooth muscle activity in GI tract | Severe diarrhea-predominant IBS in women | Oral | Rare but serious constipation; ischemic colitis • bowel infarction |
Anticholinergics: nonselective action on GI activity; associated with typical antimuscarinic toxicity Chloride channel activator: lubiprostone is useful in constipation-predominant IBS in women |
Antiemetics |
5-HT3antagonists (eg, ondansetron) | 5-HT3receptor block in GI and CNS | Prevention of chemotherapy-induced and postoperative nausea and vomiting | Oral and parenteral formulations | May slow colonic transit |
Other 5-HT3antagonist antiemetics: dolasetron, granisetron, palonosetron; see Chapter 16 Corticosteroids: mechanism not known but useful in antiemetic IV cocktails; see Chapter 39 Antimuscarinics (eg, scopolamine): effective in emesis due to motion sickness; not other types; see Chapter 8 Phenothiazines: act primary through block of D2and muscarinic receptors; see Chapter 16 Cannabinoids: dronabinol is available for use in chemotherapy-induced nausea and vomiting, but is associated with CNS marijuana effects (see Chapter 32) Aprepitant: A neurokinin 1 (NK1) antagonist available for use in chemotherapy-induced nausea and vomiting; associated with fatigue, dizziness, diarrhea, and CYP interactions |
Drugs for inflammatory bowel disease (IBD) |
Mesalamine (5-aminosalicylate) | Mechanism uncertain • may be inhibition of eicosanoid inflammatory mediators | Mild to moderately severe Crohn's disease and ulcerative colitis | Various formulations designed to deliver drug to distal ileum and colon | Little or no toxicity |
Azo compounds: dalsalazide, olsalazine, sulfasalazine; colonic bacterial azoreductase enzymes release 5-aminosalicylate in the colon; sulfasalazine can cause sulfonamide toxicity due to absorption of the sulfapyridine moiety Glucocorticoids: see Chapters 30 and 55 Immunosuppressant antimetabolites: see Chapters 54 and 55 Anti-TNF drugs: see Chapters 36 and 55 Natalizumab: antibody that blocks leukocyte integrins; may cause multifocal leukoencephalopathy |
Pancreatic supplements |
Pancrelipase | Replacement enzymes from animal pancreatic extracts that improve digestion of fat, protein, and carbohydrate | Pancreatic insufficiency due to cystic fibrosis, pancreatitis, pancreatectomy | Taken with every meal | May increase incidence of gout |
Pancreatin: similar pancreatic extracts but much lower potency; rarely used |
Bile acid therapy for gallstones |
Ursodiol | Reduces cholesterol secretion into bile | Gallstones in patients refusing or not eligible for surgery | Oral | Little or no toxicity |