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Enzyme Induction — FRCA Primary MCQ

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ModeratePharmacology - General PrinciplesEnzyme InductionFRCA Primary

A patient stabilised on long-term oral medication is started on rifampicin, a potent inducer of drug-metabolising enzymes. Which of the following statements about enzyme induction is correct?

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Correct answer: BIt reflects increased gene transcription and de novo synthesis of cytochrome P450 protein, chiefly CYP3A4

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

Enzyme induction is a transcriptional event: rifampicin activates the nuclear pregnane X receptor, increasing CYP3A4 mRNA and hence synthesis of new enzyme protein (the UK SmPC lists CYP1A2, 2B6, 2C8, 2C9, 2C19 and 3A4 as induced). Because new protein must be made and enzyme pools turn over, the clinical effect develops over days to weeks, not minutes — so E is wrong; E also over-states the outcome, since increased metabolism usually reduces substrate exposure and effect (it increases effect or toxicity only when an active or toxic metabolite is formed). B describes an active-site interaction, the mechanism of competitive inhibition, not induction. C is wrong: CYP2D6 is not among the rifampicin-inducible isoforms and is essentially non-inducible. D confuses enzyme induction with perfusion-limited clearance; moreover, reduced flow would lower, not raise, clearance of high-extraction drugs.

Reference: Rifampicin 300 mg Capsules — Summary of Product Characteristics, section 4.5 (Induction of drug metabolising enzymes and transporters), electronic Medicines Compendium (eMC), current version. https://www.medicines.org.uk/emc/product/8789/smpc