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Precipitated Withdrawal Mechanism — MRCPsych Paper B MCQ

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HardSubstance MisusePrecipitated Withdrawal MechanismMRCPsych Paper B

A man with established heroin dependence receives his first dose of sublingual buprenorphine 2 hours after injecting heroin. At that point he is mildly sedated with pinpoint pupils and has no objective signs of withdrawal. Within 30 minutes he develops marked agitation, sweating, piloerection, mydriasis, abdominal cramps and diarrhoea. Which receptor-level mechanism best explains this reaction?

Educational content. Not a substitute for clinical judgement or local policy.

Reveal the answer and explanation

Correct answer: A — High-affinity partial mu-opioid agonism displaces the full agonist and abruptly lowers net receptor activation

Explanation lettering: B = shown as A · C = shown as B · D = shown as C · E = shown as D · A = shown as E

Buprenorphine is a high-affinity partial agonist at the mu-opioid receptor. Given while heroin-derived full agonists still substantially occupy and activate the receptor, buprenorphine displaces them but supplies lower intrinsic activity, so net mu signalling falls abruptly and precipitated withdrawal follows — hence B. A is wrong because buprenorphine is not a full agonist and increased mu activation would deepen intoxication, not withdrawal. D overstates the pharmacology: buprenorphine has appreciable, not zero, mu intrinsic efficacy. C inverts the affinity relationship — buprenorphine's affinity exceeds heroin's metabolites, which is why displacement occurs. E is a real property (kappa antagonism) but does not mediate precipitated withdrawal. Induction should await objective withdrawal signs rather than elapsed time alone.

Reference: NICE TA114, Methadone and buprenorphine for the management of opioid dependence, section 3 'The technologies' (2007, current published guidance): https://www.nice.org.uk/guidance/ta114/chapter/3-the-technologies