Codeine CYP2D6 Metabolism — MFDS Part 1 MCQ

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ModeratePharmacologyCodeine CYP2D6 MetabolismMFDS Part 1

An adult develops marked somnolence and miosis after taking a standard therapeutic dose of codeine for acute postoperative dental pain. Genotyping subsequently identifies a CYP2D6 ultra-rapid-metaboliser phenotype. Which mechanism best explains this response?

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Correct answer: D — Increased hepatic conversion of codeine to morphine

The correct answer is D. Codeine has relatively low affinity for μ-opioid receptors, and its analgesic and toxic opioid effects depend substantially on hepatic CYP2D6-mediated conversion to morphine. A CYP2D6 ultra-rapid metaboliser can therefore generate higher-than-expected morphine concentrations from a standard codeine dose, producing features such as somnolence, miosis and potentially respiratory depression. Conversely, patients with deficient CYP2D6 activity may obtain inadequate analgesia. Direct receptor binding by unchanged codeine contributes little compared with morphine formation. Codeine does not act by inhibiting cyclo-oxygenase, modulating GABA receptors or blocking voltage-gated sodium channels; these mechanisms are associated with other classes of analgesic or centrally acting medicines.

Reference: Electronic Medicines Compendium, Codeine Phosphate Tablets BP 30mg, Summary of Product Characteristics, sections 4.4 and 5.2 (current version). https://www.medicines.org.uk/emc/product/2616/smpc