Wattle Pharmacy Prep

Metabolism and cytochrome P450
Practice questions with explanations

Metabolism and cytochrome P450 belongs to Pharmacokinetics and pharmacodynamics, which makes up about 10% of the Overseas Pharmacist Readiness Assessment (OPRA®). Answer each question yourself before opening the explanation.

1. Which consequence follows from CYP3A4 being present in the intestinal wall as well as the liver?

  1. It has no effect on oral drugs
  2. Oral bioavailability of substrates is reduced by intestinal first-pass metabolism, and intestinal inhibition alone can raise exposure substantially
  3. Only intravenous drugs are affected
  4. It increases oral bioavailability
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B. Oral bioavailability of substrates is reduced by intestinal first-pass metabolism, and intestinal inhibition alone can raise exposure substantially

Grapefruit acts almost entirely on intestinal CYP3A4, which is why it affects oral but not intravenous administration of the same drug, and why the size of the effect depends on how much first-pass metabolism occurs in the gut. Intestinal P-glycoprotein works alongside it, often on the same substrates.

2. What distinguishes phase I from phase II metabolism?

  1. Phase II always precedes phase I
  2. Phase I always inactivates a drug and phase II always activates it
  3. Phase I occurs in the kidney and phase II in the liver
  4. Phase I introduces or exposes a functional group by oxidation, reduction or hydrolysis; phase II conjugates it to a polar endogenous molecule
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D. Phase I introduces or exposes a functional group by oxidation, reduction or hydrolysis; phase II conjugates it to a polar endogenous molecule

Phase I reactions, mostly cytochrome P450 oxidations, add or unmask a handle such as a hydroxyl group. Phase II attaches glucuronic acid, sulfate, glutathione, acetyl or methyl groups to that handle, producing a water-soluble conjugate for excretion. Either phase can create an active or a toxic metabolite, and a drug that already has a suitable group can go straight to phase II, so the numbering describes chemistry rather than a fixed order.

3. Which enzyme system does St John's wort chiefly affect, and with what result?

  1. It induces CYP2D6 exclusively
  2. It inhibits CYP3A4, raising drug concentrations
  3. It affects only serotonin reuptake and has no metabolic effect
  4. It induces CYP3A4 and P-glycoprotein, lowering concentrations of many drugs including contraceptives, ciclosporin and some antivirals
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D. It induces CYP3A4 and P-glycoprotein, lowering concentrations of many drugs including contraceptives, ciclosporin and some antivirals

Hyperforin activates the pregnane X receptor, inducing CYP3A4 and the efflux transporter P-glycoprotein. The clinical results have included contraceptive failure, transplant rejection through loss of ciclosporin cover, and antiretroviral failure. It can also add to serotonergic effects. Being available without prescription and often unmentioned by patients, it is one of the interactions worth asking about directly.

These are 3 of the 40 questions on metabolism and cytochrome p450 in the app.

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More topics in Pharmacokinetics and pharmacodynamics

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