Which medication produces long-acting ACTIVE metabolites, prolonging its clinical effect?

Correct answer: D. Diazepam

• A. ❌ Lidocaine's metabolites are largely inactive, though they contribute to CNS toxicity at high plasma levels.
• B. ❌ Lisinopril is unusual among ACE inhibitors precisely BECAUSE it is not a prodrug and is excreted unchanged — enalapril and ramipril are the ones requiring hepatic activation.
• C. ❌ Midazolam's principal metabolite, 1-hydroxymidazolam, has minimal clinical activity in normal renal function, which is why midazolam is preferred for short procedures.
• D. ✅ CORRECT — DIAZEPAM is metabolized to desmethyldiazepam (nordiazepam), oxazepam and temazepam, all pharmacologically active. Desmethyldiazepam has a half-life approaching 100 hours, which explains diazepam's prolonged and cumulative sedation, especially in elderly patients.

Note: Benzodiazepines with NO active metabolites — safer in the elderly and in liver disease: Lorazepam, Oxazepam, Temazepam (mnemonic: LOT).