PSA Drug Interactions 2 — Questions and Answers
Question 1: A patient stabilized on warfarin begins rifampicin for tuberculosis. What is the most likely effect on the INR?
- INR increases due to CYP2C9 inhibition by rifampicin
- INR decreases due to CYP2C9 induction by rifampicin (Correct answer)
- No change because warfarin is not hepatically metabolized
- INR increases due to rifampicin reducing vitamin K synthesis
Correct answer: INR decreases due to CYP2C9 induction by rifampicin
Rifampicin is a potent CYP2C9 inducer that accelerates warfarin metabolism, substantially reducing its anticoagulant effect and lowering the INR.
Question 2: A patient on simvastatin 40 mg is prescribed clarithromycin for a respiratory infection. What is the primary risk?
- Reduced simvastatin efficacy due to enzyme induction
- Decreased clarithromycin absorption due to altered gastric pH
- Increased risk of myopathy or rhabdomyolysis due to elevated simvastatin levels (Correct answer)
- Cardiac arrhythmia from combined QT prolongation
Correct answer: Increased risk of myopathy or rhabdomyolysis due to elevated simvastatin levels
Clarithromycin potently inhibits CYP3A4, the primary enzyme metabolizing simvastatin, causing plasma accumulation and a significantly increased risk of muscle toxicity.
Question 3: A patient receiving standard-dose codeine reports no pain relief. Which CYP enzyme variant most likely explains this pharmacogenomic interaction?
- CYP2C9 poor metabolizer reducing codeine clearance
- CYP3A4 ultra-rapid metabolizer accelerating codeine activation
- CYP1A2 poor metabolizer altering codeine glucuronidation
- CYP2D6 poor metabolizer preventing conversion of codeine to morphine (Correct answer)
Correct answer: CYP2D6 poor metabolizer preventing conversion of codeine to morphine
CYP2D6 converts codeine to its active analgesic metabolite morphine; poor metabolizers (7–10% of Caucasians) derive minimal analgesia from codeine.
Question 4: Fluoxetine (a potent CYP2D6 inhibitor) is started in a patient already taking tramadol. What is the most important risk?
- Reduced tramadol efficacy from blocked O-desmethylation
- Atorvastatin toxicity via shared CYP2D6 competition
- Tramadol accumulation and serotonin syndrome risk due to CYP2D6 inhibition (Correct answer)
- Warfarin potentiation from CYP2C9 cross-inhibition
Correct answer: Tramadol accumulation and serotonin syndrome risk due to CYP2D6 inhibition
Fluoxetine inhibits CYP2D6, which metabolizes tramadol to its active form; inhibition elevates parent tramadol levels and impairs serotonin reuptake clearance, raising serotonin syndrome risk.
Question 5: A patient on combined oral contraceptives starts carbamazepine for epilepsy. What is the pharmacokinetic mechanism of concern?
- CYP3A4 induction by carbamazepine reduces estrogen and progestogen plasma levels (Correct answer)
- CYP3A4 inhibition by carbamazepine increases hormone exposure
- Carbamazepine displaces estrogen from albumin binding sites
- Direct pharmacodynamic antagonism at estrogen receptors
Correct answer: CYP3A4 induction by carbamazepine reduces estrogen and progestogen plasma levels
Carbamazepine is a potent CYP3A4 inducer that accelerates hepatic metabolism of ethinylestradiol and progestogens, reducing contraceptive hormone levels and risking contraceptive failure.
Question 6: Omeprazole co-prescription reduces the antiplatelet efficacy of clopidogrel. What is the mechanism?
- Pharmacodynamic competition at platelet P2Y12 receptors
- CYP2C19 inhibition by omeprazole reduces conversion of clopidogrel to its active thiol metabolite (Correct answer)
- Omeprazole induces P-glycoprotein efflux of clopidogrel from enterocytes
- Alkaline gastric pH from omeprazole reduces clopidogrel dissolution and absorption
Correct answer: CYP2C19 inhibition by omeprazole reduces conversion of clopidogrel to its active thiol metabolite
Clopidogrel is a prodrug requiring CYP2C19 for bioactivation; omeprazole inhibits this enzyme, reducing formation of the active metabolite and diminishing platelet P2Y12 inhibition.
Question 7: A patient on long-term methadone maintenance is started on phenytoin for new-onset seizures. What is the anticipated outcome?
- Phenytoin toxicity from methadone-mediated CYP2C9 inhibition
- Serotonin syndrome from combined opioid and anticonvulsant CNS effects
- Methadone toxicity from decreased hepatic clearance
- Opioid withdrawal symptoms from phenytoin-induced increase in methadone clearance (Correct answer)
Correct answer: Opioid withdrawal symptoms from phenytoin-induced increase in methadone clearance
Phenytoin is a broad enzyme inducer (CYP3A4, CYP2C9) that significantly accelerates methadone metabolism, precipitating opioid withdrawal in dependent patients.
PSA Drug Interactions 2
A patient stabilized on warfarin begins rifampicin for tuberculosis.
What is the most likely effect on the INR?