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Morphine Metabolites — FRCA Primary MCQ

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ModeratePharmacology - AnalgesicsMorphine MetabolitesFRCA Primary

A patient with stage 5 chronic kidney disease develops delayed and prolonged respiratory depression after repeated doses of morphine. Which statement about morphine glucuronide metabolites best explains this?

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Correct answer: B — M6G is an active opioid-receptor agonist that accumulates when renal clearance is reduced

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

A is correct. Morphine is glucuronidated principally to M3G and, to a lesser extent, M6G. M6G is an active opioid-receptor agonist, acting predominantly through μ receptors, and contributes to analgesia and respiratory depression. Morphine glucuronides are eliminated mainly by the kidneys; therefore reduced renal clearance permits M6G accumulation and can cause delayed, prolonged CNS and respiratory depression. M3G lacks clinically useful analgesic opioid activity, although high concentrations may contribute to neuroexcitatory effects. Consequently, B and E incorrectly describe M6G as inactive, while C and D incorrectly attribute potent opioid analgesia to M3G. Toxicity in renal failure cannot be attributed solely to accumulation of unchanged morphine.

Reference: Wockhardt UK Ltd. Morphine Sulfate 10mg/5ml Oral Solution, Summary of Product Characteristics, sections 4.4 and 5.2; revised 11 October 2023. https://www.medicines.org.uk/emc/product/2629/smpc