Which of the following statements about H2-receptor antagonists is correct?

Explanation

## H2-Receptor Antagonists — Mechanism and Pharmacokinetics **Key Point:** H2 blockers are **competitive antagonists** at histamine H2 receptors on parietal cells. They are not prodrugs and do not irreversibly inhibit acid secretion. ### Mechanism of Action | Feature | H2 Blockers | PPIs | |---------|-----------|------| | **Receptor target** | Histamine H2 receptor (competitive antagonism) | H^+^/K^+^-ATPase pump (irreversible inhibition) | | **Activation** | Active as administered; no prodrug activation | Prodrug; requires acid-catalyzed activation | | **Binding** | Reversible, competitive | Irreversible, covalent | | **Duration of action** | 8–12 hours (cimetidine, ranitidine, famotidine) | 24–72 hours (despite short plasma half-life) | | **Acid suppression** | ~70% reduction | ~90% reduction | | **Onset** | 30–60 minutes | 3–5 days to steady state | ### H2 Blocker Pharmacology **High-Yield:** H2 blockers: - Block histamine-mediated stimulation of cAMP → reduced acid secretion - Also inhibit acid secretion stimulated by gastrin and acetylcholine (partial effect) - Have shorter duration than PPIs because binding is reversible - Reach steady-state inhibition within 24–48 hours (not 3–5 days) - Can be used for acute symptom relief (faster onset than PPIs) **Mnemonic — H2 Blockers:** **"CRAF"** = Cimetidine, Ranitidine, Famotidine, (and Nizatidine). All are reversible competitive antagonists. **Clinical Pearl:** H2 blockers are less potent than PPIs for severe GERD or peptic ulcer disease, but are useful for mild-to-moderate symptoms and as maintenance therapy. They have fewer drug interactions than older H2 blockers (cimetidine inhibits CYP450; newer agents do not). [cite:Harrison 21e Ch 297]