A 35-year-old woman with alcohol use disorder has been abstinent for two months. She is started on a medication that causes severe flushing, palpitations, nausea, and vomiting if she consumes any alcohol. Which enzyme does this drug inhibit?

• A Alcohol dehydrogenase
• B CYP2E1
• C Monoamine oxidase
• D Aldehyde dehydrogenase ✓

Explanation

Disulfiram inhibits aldehyde dehydrogenase, blocking the second step of alcohol metabolism. Acetaldehyde, which is normally oxidised to acetate, accumulates and produces the disulfiram-ethanol reaction: flushing, nausea, tachycardia, and hypotension. This aversive reaction is the therapeutic mechanism. Alcohol dehydrogenase catalyses the first step (ethanol to acetaldehyde) and is not inhibited by disulfiram. Naltrexone (opioid antagonist) and acamprosate (glutamate/GABA modulator) are other approved maintenance treatments for alcohol use disorder.

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

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