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Buprenorphine mechanism — MRCPsych Paper A MCQ

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ModeratePsychopharmacologyBuprenorphine mechanismMRCPsych Paper A

A 31-year-old woman with heroin dependence is due to start sublingual buprenorphine. She is advised not to take the first dose until objective signs of mild-to-moderate opioid withdrawal are present, because administering it earlier can precipitate withdrawal. Which pharmacological property of buprenorphine best explains this risk?

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Correct answer: A — High-affinity partial agonism at μ-opioid receptors

Buprenorphine is a high-affinity partial agonist at μ-opioid receptors. If administered while heroin or another full μ-agonist is still exerting an effect, buprenorphine displaces it but produces less intrinsic receptor activation, causing a rapid net reduction in opioid effect and precipitated withdrawal. Induction should therefore occur once objective withdrawal is established. Low-affinity full agonism would not explain displacement and resembles neither buprenorphine nor its induction risk. A high-affinity pure μ-antagonist could precipitate withdrawal, but buprenorphine is not a pure antagonist. Its clinically relevant κ action is antagonism rather than partial agonism, while irreversible δ-receptor antagonism does not describe its mechanism.

Reference: Electronic Medicines Compendium. Buprenorphine 8 mg sublingual tablets, Summary of Product Characteristics (sections 4.2, 4.4, 5.1). https://www.medicines.org.uk/emc/product/2050/smpc