GI, Renal & Urology

Proton pump inhibitors (omeprazole, pantoprazole, esomeprazole, lansoprazole, rabeprazole, dexlansoprazole) irreversibly inhibit the H+/K+-ATPase (gastric proton pump) on the apical membrane of parietal cells, blocking the final common step of acid secretion. They are prodrugs activated in the acidic secretory canaliculus, so they work best taken 30-60 min before a meal when pumps are active.

Long-term/high-dose PPI use is associated with hypomagnesemia (check Mg with prolonged use), vitamin B12 deficiency, decreased calcium absorption with increased fracture risk, hypochlorhydria-related infections (C. difficile, community-acquired pneumonia), acute interstitial nephritis, and possible rebound hyperacidity on discontinuation. Use lowest effective dose for shortest duration.

PPIs are metabolized by and can inhibit CYP2C19. Omeprazole and esomeprazole most strongly inhibit CYP2C19, reducing conversion of clopidogrel to its active metabolite and potentially blunting antiplatelet effect; pantoprazole has the least interaction and is preferred with clopidogrel. PPIs also reduce absorption of pH-dependent drugs (atazanavir, ketoconazole/itraconazole, oral iron, certain TKIs).

H2RAs (famotidine, cimetidine, nizatidine) competitively block histamine H2 receptors on parietal cells, reducing basal and nocturnal acid secretion. Less potent than PPIs; useful for mild GERD, nocturnal acid breakthrough, and on-demand use. Tolerance (tachyphylaxis) can develop within 2 weeks. Doses require renal adjustment.

Cimetidine is a potent inhibitor of multiple CYP enzymes (1A2, 2C19, 2D6, 3A4), raising levels of warfarin, phenytoin, theophylline, and others. It also has antiandrogenic effects causing gynecomastia and can cause confusion in the elderly/renal impairment. Famotidine is preferred because it lacks these significant interactions.

Preferred first-line is bismuth quadruple therapy (PPI + bismuth subsalicylate + metronidazole + tetracycline) for 14 days, especially with prior macrolide exposure or high clarithromycin resistance. Alternative is clarithromycin triple therapy (PPI + clarithromycin + amoxicillin) only where resistance <15% and no prior macrolide use. Rifabutin-based and levofloxacin regimens are salvage options.