Disulfiram Mechanism — MRCPsych Paper B MCQ

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EasySubstance MisuseDisulfiram MechanismMRCPsych Paper B

A 50-year-old man with alcohol dependence starts disulfiram following successful alcohol withdrawal. If he consumes alcohol, he develops flushing, nausea, palpitations and hypotension. Which pharmacological mechanism most directly produces this reaction?

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Correct answer: D — Irreversible aldehyde dehydrogenase inhibition

Disulfiram irreversibly inhibits hepatic aldehyde dehydrogenase. If alcohol is consumed, ethanol is converted to acetaldehyde but its further metabolism is impaired, causing acetaldehyde accumulation. This produces the aversive disulfiram–alcohol reaction, characterised by flushing, nausea, vomiting, headache, palpitations and hypotension; severe reactions may include arrhythmias, cardiovascular collapse or convulsions. NMDA receptor modulation is associated with acamprosate, while μ-opioid receptor antagonism is the principal mechanism of naltrexone. GABA-A receptor agonism describes the action of benzodiazepines used during assisted alcohol withdrawal rather than disulfiram. Serotonin reuptake inhibition is the mechanism of SSRIs and does not account for this alcohol-triggered reaction.

Reference: Brown & Burk UK Ltd. Disulfiram 200 mg tablets, Summary of Product Characteristics, sections 4.8 and 5.1. Updated 17 October 2025. https://www.medicines.org.uk/emc/product/11168/smpc