General pharmacology: CYP2D6 and tamoxifen: 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: CYP2D6 and tamoxifen

Sample item

A woman with oestrogen receptor positive breast cancer on tamoxifen develops depression and is started on paroxetine. Why might tamoxifen efficacy fall?

AParoxetine blocks oestrogen receptors competitivelyBParoxetine induces CYP3A4 and speeds tamoxifen clearanceCParoxetine displaces tamoxifen from albuminDParoxetine inhibits CYP2D6, reducing formation of the active metabolite endoxifen

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

The answer and the reasoning

D. Paroxetine inhibits CYP2D6, reducing formation of the active metabolite endoxifen

Tamoxifen is a prodrug converted largely by CYP2D6 to endoxifen, its most active metabolite. Strong CYP2D6 inhibitors such as paroxetine and fluoxetine, or poor metaboliser genotypes, lower endoxifen and may reduce benefit.

Option by option

A. Paroxetine blocks oestrogen receptors competitively
Paroxetine has no oestrogen receptor blocking action.
B. Paroxetine induces CYP3A4 and speeds tamoxifen clearance
Paroxetine is an inhibitor, not an inducer, of drug metabolising enzymes.
C. Paroxetine displaces tamoxifen from albumin
Protein-binding displacement does not reduce efficacy in this way.
D. Paroxetine inhibits CYP2D6, reducing formation of the active metabolite endoxifen (correct)
Correct. CYP2D6 inhibition reduces activation of the prodrug.

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.

Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is D, Paroxetine inhibits CYP2D6, reducing formation of the active metabolite endoxifen. Tamoxifen is a prodrug converted largely by CYP2D6 to endoxifen, its most active metabolite.

Why is "Paroxetine blocks oestrogen receptors competitively" not the answer?

Paroxetine has no oestrogen receptor blocking action.

Why is "Paroxetine induces CYP3A4 and speeds tamoxifen clearance" not the answer?

Paroxetine is an inhibitor, not an inducer, of drug metabolising enzymes.

Why is "Paroxetine displaces tamoxifen from albumin" not the answer?

Protein-binding displacement does not reduce efficacy in this way.

What concept does this question test?

It tests General pharmacology: CYP2D6 and tamoxifen in Pharmacology. Strong CYP2D6 inhibitors such as paroxetine and fluoxetine, or poor metaboliser genotypes, lower endoxifen and may reduce benefit.

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: CYP2D6 and tamoxifen?

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.