RH Herb-Drug Interaction Pharmacology 2 — Questions and Answers
Question 1: Which CYP450 enzyme is most significantly induced by St. John's Wort, leading to reduced plasma levels of many drugs?
- CYP1A2
- CYP2D6
- CYP3A4 (Correct answer)
- CYP2C9
Correct answer: CYP3A4
St. John's Wort potently induces CYP3A4, which metabolizes roughly 50% of all drugs, causing therapeutic failure.
Question 2: A patient on cyclosporine for organ transplant begins taking St. John's Wort. What is the primary clinical concern?
- Increased cyclosporine toxicity
- Organ rejection due to subtherapeutic cyclosporine levels (Correct answer)
- Additive immunosuppression
- Elevated serum creatinine unrelated to cyclosporine
Correct answer: Organ rejection due to subtherapeutic cyclosporine levels
St. John's Wort induces CYP3A4 and P-glycoprotein, dramatically lowering cyclosporine levels and risking acute organ rejection.
Question 3: Goldenseal (Hydrastis canadensis) inhibits which CYP450 enzyme, potentially increasing toxicity of drugs metabolized by it?
- CYP3A4
- CYP2D6 (Correct answer)
- CYP1A2
- CYP2E1
Correct answer: CYP2D6
Goldenseal's berberine and hydrastine inhibit CYP2D6, slowing metabolism of drugs like codeine, dextromethorphan, and some antidepressants.
Question 4: P-glycoprotein (P-gp) is an efflux transporter important in herb-drug interactions. Which herb is a known inducer of P-gp?
- Kava
- Ginger
- St. John's Wort (Correct answer)
- Valerian
Correct answer: St. John's Wort
St. John's Wort induces P-gp efflux transport, reducing intestinal absorption and increasing renal/biliary elimination of substrate drugs.
Question 5: Which pharmacokinetic phase is primarily affected when a herb inhibits intestinal CYP3A4?
- Distribution
- First-pass metabolism / absorption (Correct answer)
- Renal excretion
- Protein binding
Correct answer: First-pass metabolism / absorption
Inhibiting intestinal CYP3A4 reduces first-pass metabolism, increasing oral bioavailability of substrate drugs.
Question 6: Grapefruit juice is commonly cited as a CYP3A4 inhibitor. Which constituent is responsible for this effect?
- Naringenin glycosides
- Furanocoumarins (e.g., bergamottin) (Correct answer)
- Flavonoids like quercetin
- Limonene
Correct answer: Furanocoumarins (e.g., bergamottin)
Furanocoumarins in grapefruit juice irreversibly inhibit intestinal CYP3A4, increasing levels of many drugs.
Question 7: A patient taking warfarin starts high-dose vitamin E supplementation. The expected interaction involves:
- Induction of CYP2C9 reducing warfarin levels
- Additive anticoagulant effect increasing bleeding risk (Correct answer)
- Competitive binding at vitamin K receptors reducing anticoagulation
- Displacement of warfarin from albumin causing toxicity then rapid clearance
Correct answer: Additive anticoagulant effect increasing bleeding risk
High-dose vitamin E inhibits platelet aggregation and may interfere with vitamin K-dependent clotting factors, adding to warfarin's anticoagulant effect.
RH Herb-Drug Interaction Pharmacology 2
Which CYP450 enzyme is most significantly induced by St.
John's Wort, leading to reduced plasma levels of many drugs?