Match each clinical scenario describing a pharmacokinetic drug interaction to the primary underlying molecular mechanism responsible for the altered drug levels.
- Rifampin is prescribed to a patient stabilized on warfarin, leading to a gradual decrease in the international normalized ratio (INR).Increased transcription and expression of hepatic cytochrome P450 enzymes
- Probenecid is administered alongside cephalexin, significantly increasing the half-life and serum concentration of the cephalosporin.Competitive inhibition of organic anion transporters (OAT) in the renal proximal tubule
- Verapamil is initiated in a patient taking digoxin, precipitating nausea, visual changes, and a prolonged PR interval.Inhibition of intestinal and renal P-glycoprotein (P-gp) efflux transporters
- A patient stabilized on felodipine begins drinking grapefruit juice daily, presenting subsequently with symptomatic hypotension and peripheral edema.Mechanism-based (irreversible) inhibition of intestinal cytochrome P450 enzymes
Answer
Rifampin decreases warfarin levels via CYP450 induction; Probenecid increases cephalexin levels via OAT inhibition; Verapamil increases digoxin levels via P-glycoprotein inhibition; Grapefruit juice increases felodipine levels via intestinal CYP3A4 inhibition.
Each clinical scenario describes a classic pharmacokinetic interaction. Rifampin induces CYP450 enzymes, lowering warfarin levels. Probenecid inhibits renal OATs, raising beta-lactam levels. Verapamil inhibits P-gp, raising digoxin levels. Grapefruit juice inhibits intestinal CYP3A4, raising felodipine levels.
Step-by-Step Solution
Key Concept
Understanding the pharmacokinetic mechanisms of major drug-drug interactions is essential for predicting and preventing adverse clinical outcomes.
Estimated Time:1m 30s