Disulfiram is prescribed to a motivated patient with alcohol use disorder along with supervised administration. Its deterrent effect depends on which mechanism?

• A Blockade of mu-opioid receptors, abolishing alcohol-induced euphoria
• B Inhibition of aldehyde dehydrogenase, causing acetaldehyde accumulation with flushing, vomiting and hypotension if alcohol is consumed ✓
• C Partial agonism at GABA-A receptors, substituting for alcohol's sedative effect
• D Inhibition of alcohol dehydrogenase, preventing ethanol metabolism entirely

Explanation

Disulfiram irreversibly inhibits aldehyde dehydrogenase, the enzyme converting acetaldehyde to acetate. Alcohol ingestion then produces the disulfiram-alcohol reaction: flushing, throbbing headache, nausea, vomiting, palpitations and hypotension, mediated by accumulated acetaldehyde. This aversive consequence underlies its use only in adherent, motivated patients. Naltrexone works by opioid receptor blockade, killing option A, and acamprosate acts on glutamate and GABA systems, killing option C. Inhibiting alcohol dehydrogenase would raise blood ethanol, not deter drinking.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

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