Disulfiram (Antabuse) for alcohol use disorder works by inhibiting which enzyme, leading to accumulation of acetaldehyde?

• A Alcohol dehydrogenase
• B CYP2E1
• C Catalase
• D Aldehyde dehydrogenase (ALDH) ✓

Explanation

Disulfiram irreversibly inhibits aldehyde dehydrogenase (ALDH), the enzyme responsible for oxidizing acetaldehyde (a toxic metabolite of ethanol) to acetate. When a patient on disulfiram drinks alcohol, acetaldehyde accumulates, producing flushing, nausea, vomiting, tachycardia, and hypotension—the disulfiram-ethanol reaction (DER), which creates an aversive deterrent to drinking. Alcohol dehydrogenase converts ethanol to acetaldehyde (first step); CYP2E1 is an alternative oxidation pathway for ethanol; catalase plays a minor role in ethanol metabolism.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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Written and medically reviewed by the StethoPrep medical team.