General pharmacology and pharmacokinetics: CYP2D6 ultra-rapid metabolisers: practice question

A Pharmacology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pharmacology · General pharmacology and pharmacokinetics: CYP2D6 ultra-rapid metabolisers

Sample item

A breastfeeding mother who is an ultra-rapid CYP2D6 metaboliser takes codeine for post-caesarean pain. Her infant becomes lethargic with slow breathing. What is the likely mechanism?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

D. Excess O-demethylation of codeine to morphine

CYP2D6 converts codeine to morphine, which accounts for most of its analgesia. Ultra-rapid metabolisers form unusually large amounts of morphine, which passes into breast milk and can depress the infant's respiration. Codeine is avoided in such mothers.

Option by option

  • A. Accumulation of inactive norcodeine in milk

    Norcodeine is a minor and weakly active metabolite that does not cause respiratory depression.

  • B. Reduced glucuronidation of codeine in the infant

    Codeine itself is weakly active, and impaired glucuronidation would not explain this picture in the context of the mother's genotype.

  • C. Inhibition of CYP3A4 by codeine in the mother

    Codeine does not inhibit CYP3A4 to a clinically relevant extent.

  • D. Excess O-demethylation of codeine to morphine (correct)

    Correct. Rapid conversion to morphine gives a high morphine load in the milk.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is D, Excess O-demethylation of codeine to morphine. CYP2D6 converts codeine to morphine, which accounts for most of its analgesia.

Why is "Accumulation of inactive norcodeine in milk" not the answer?

Norcodeine is a minor and weakly active metabolite that does not cause respiratory depression.

Why is "Reduced glucuronidation of codeine in the infant" not the answer?

Codeine itself is weakly active, and impaired glucuronidation would not explain this picture in the context of the mother's genotype.

Why is "Inhibition of CYP3A4 by codeine in the mother" not the answer?

Codeine does not inhibit CYP3A4 to a clinically relevant extent.

What concept does this question test?

It tests General pharmacology and pharmacokinetics: CYP2D6 ultra-rapid metabolisers in Pharmacology. Ultra-rapid metabolisers form unusually large amounts of morphine, which passes into breast milk and can depress the infant's respiration. Codeine is avoided in such mothers.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study General pharmacology and pharmacokinetics: CYP2D6 ultra-rapid metabolisers?

Learn drugs as classes, then the exception in each class that an examiner would pick. Then use the flashcards and the other Pharmacology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.