Drug Interactions MCQ — NEET PG Practice Question | NEETPGAI
Drug Interactions
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pill Pharmacology
A 58-year-old man with atrial fibrillation on warfarin (INR 2.5) presents to the clinic. He was recently started on fluconazole 400 mg daily for oral candidiasis. Two weeks later, his INR is 4.8 and he reports spontaneous bruising on his arms. What is the mechanism of this drug interaction?
A. Fluconazole inhibits CYP2C9, reducing warfarin metabolism and increasing its anticoagulant effect
B. Fluconazole inhibits vitamin K synthesis in the gut, potentiating warfarin's effect
C. Fluconazole induces CYP3A4, increasing warfarin clearance and reducing its efficacy
D. Fluconazole displaces warfarin from plasma protein binding, increasing free drug concentration
Explanation
Drug Interaction Mechanism
Key Point
Fluconazole is a potent inhibitor of CYP2C9, the primary enzyme responsible for warfarin metabolism. This inhibition leads to decreased warfarin clearance, elevated plasma concentrations, and increased anticoagulant effect.
Warfarin Metabolism & CYP2C9
Warfarin is metabolized via two pathways:
S-warfarin (more potent): CYP2C9 → major route (~90% of anticoagulant effect)
R-warfarin (less potent): CYP2C8, CYP3A4, CYP1A2
Fluconazole's selective inhibition of CYP2C9 disproportionately affects S-warfarin elimination.
Clinical Presentation in This Case
Table
Finding
Explanation
INR rise from 2.5 → 4.8
Increased warfarin bioavailability due to reduced metabolism
CYP2C9 inhibition develops over days; warfarin half-life is 36–42 hours, so steady-state elevation occurs by week 2
Management
High-YieldNEET PG
When CYP2C9 inhibitors are co-prescribed with warfarin:
1.
Monitor INR closely (every 3–5 days initially)
2.
Reduce warfarin dose by 20–30%
3.
Consider alternative antifungal (e.g., nystatin for oral candidiasis, which is not absorbed and has no interaction)
Clinical Pearl
Other CYP2C9 inhibitors that interact with warfarin include amiodarone, NSAIDs, sulfonamides, and metronidazole — all require INR monitoring and dose adjustment.
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