An alcoholic patient treated with disulfiram ingests a small quantity of alcohol and develops severe flushing, palpitations, nausea, and hypotension. The biochemical mechanism of this reaction involves accumulation of which compound?

• A Acetate
• B Acrolein
• C Acetone
• D Acetaldehyde ✓

Explanation

Disulfiram inhibits aldehyde dehydrogenase (ALDH), blocking the conversion of acetaldehyde to acetate. Alcohol is normally metabolised: ethanol → acetaldehyde (by alcohol dehydrogenase) → acetate (by ALDH). When ALDH is inhibited, acetaldehyde accumulates, causing the disulfiram-ethanol reaction (DER): vasodilation, flushing, tachycardia, nausea, vomiting, and hypotension. Acetate is the non-toxic downstream product that cannot be formed. The aversive conditioning from the DER deters further alcohol use.

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

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