Codeine CYP2D6 Metabolism — FRCA Primary MCQ

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ModeratePharmacology - AnalgesicsCodeine CYP2D6 MetabolismFRCA Primary

Which active metabolite is formed from codeine by CYP2D6-mediated O-demethylation and accounts for its CYP2D6-dependent analgesic effect?

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Correct answer: E — Morphine

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

C is correct. CYP2D6 O-demethylates codeine to morphine, an active μ-opioid receptor agonist responsible for the CYP2D6-dependent component of codeine analgesia. Poor CYP2D6 metabolisers therefore obtain reduced or inadequate analgesia, whereas ultra-rapid metabolisers can generate unexpectedly high morphine concentrations and develop opioid toxicity. Codeine-6-glucuronide is formed by glucuronidation and may possess some opioid activity, but it is not the CYP2D6 O-demethylation product. Norcodeine is produced predominantly by CYP3A4-mediated N-demethylation and is not the principal active analgesic metabolite. Hydromorphone and dihydrocodeine are separate opioid drugs rather than relevant metabolites of codeine.

Reference: electronic Medicines Compendium, Codeine Phosphate 60 mg Tablets, Summary of Product Characteristics, sections 4.4 and 5.1, updated 11 August 2026. https://www.medicines.org.uk/emc/product/11513/smpc