Famotidine differs from cimetidine in that it lacks which property that makes cimetidine a problematic choice for long-term use in elderly patients?

Explanation

## H₂ Receptor Antagonists: Cimetidine vs. Famotidine **Key Point:** Cimetidine is a potent inhibitor of hepatic cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2D6, CYP3A4), leading to significant drug–drug interactions. Famotidine lacks this property, making it safer for polypharmacy. ### Mechanism of CYP450 Inhibition Cimetidine contains an imidazole ring that coordinates with the heme iron of cytochrome P450, forming a stable complex that inhibits enzyme activity. This leads to: 1. **Increased plasma concentrations** of drugs metabolized by CYP450 (warfarin, theophylline, propranolol, phenytoin) 2. **Prolonged drug half-lives** and risk of toxicity 3. **Clinically significant interactions** requiring dose adjustment of co-medications ### Comparison of H₂ Blockers | Property | Cimetidine | Famotidine | Ranitidine | Nizatidine | | --- | --- | --- | --- | --- | | **CYP450 Inhibition** | **Yes (potent)** | No | Minimal | Minimal | | **Drug Interactions** | High | Low | Low | Low | | **Renal Clearance** | Moderate | Requires dose adjustment in renal failure | Moderate | Moderate | | **Gynecomastia/Sexual Dysfunction** | Yes (antiandrogenic) | No | No | No | | **CNS Effects (elderly)** | Yes (confusion, delirium) | Rare | Rare | Rare | | **Preferred in Elderly** | No | **Yes** | Yes | Yes | **High-Yield:** Cimetidine is contraindicated or requires extreme caution in: - Elderly patients (CNS effects, drug interactions) - Patients on warfarin, theophylline, or other CYP450-metabolized drugs - Patients with hepatic or renal impairment **Clinical Pearl:** Famotidine has largely replaced cimetidine in clinical practice due to its superior safety profile. Cimetidine is now reserved for specific situations where its unique properties (e.g., antiandrogenic effect in certain conditions) are therapeutically desired. **Mnemonic:** **"Cimetidine = Cytochrome killer"** — Remember that cimetidine potently inhibits CYP450, whereas famotidine does not.