H2 Receptor Blockers

PPIs get all the attention, but H2 blockers remain a key option for stress ulcer prophylaxis — especially when C. difficile risk makes PPIs less desirable — and are the go-to when PPIs are contraindicated. Know when each one wins.

H2 receptor blockers — famotidine (Pepcid) is the prototype — work by competitively blocking histamine-2 receptors on gastric parietal cells. This reduces both basal and meal-stimulated acid secretion, but does not shut down the proton pump itself. That distinction matters: H2 blockers produce moderate acid suppression with faster onset (within 1 hour oral, 15-30 minutes IV) compared to PPIs, but less total acid reduction over 24 hours. Common famotidine side effects include headache, dizziness, and constipation. Indications include GERD, duodenal and gastric ulcers, Zollinger-Ellison syndrome (adjunct — dosing is much higher than standard), and stress ulcer prophylaxis in critically ill patients. Famotidine is given 20 mg PO or IV twice daily for active ulcers, 20 mg at bedtime for maintenance. Dose reduction is required in renal impairment (CrCl <50 mL/min: reduce dose by 50% or extend the interval). IV famotidine is commonly used perioperatively and in NPO patients. Unlike older H2 blockers, famotidine has minimal drug interactions because it does not significantly inhibit cytochrome P450 enzymes. Cimetidine (Tagamet), the first-generation H2 blocker, is rarely preferred now because it inhibits CYP450, causes gynecomastia and anti-androgenic effects, and crosses the blood-brain barrier causing confusion in older adults. Ranitidine (Zantac) was withdrawn from the U.S. market due to NDMA contamination concerns. Famotidine is the safest and most commonly tested H2 blocker.

Key Distinctions

Don't confuse H2 blockers (block histamine receptors, moderate suppression, fast onset) with PPIs (irreversibly block the proton pump, maximal suppression, delayed peak effect of 2-5 days). Don't confuse H2 blockers (reduce acid production, onset ~1 hour PO) with antacids (neutralize existing acid immediately, no effect on production). Students mix up cimetidine's anti-androgenic side effects with famotidine — famotidine does NOT cause gynecomastia. Remember ranitidine is no longer available; NCLEX won't expect you to recommend it, but may test why it was removed.

Clinical Pearl

Think of H2 blockers as dimming the acid lights; PPIs flip the switch off entirely. Famotidine dims fast — use it when you need quick, moderate relief.