PSA Pharmacology Principles 3 — Questions and Answers
Question 1: Rifampicin is a potent inducer of CYP3A4. A patient on long-term warfarin starts rifampicin for tuberculosis. What is the most likely clinical consequence?
- Increased INR due to higher warfarin levels
- No change in INR
- Decreased INR due to increased warfarin metabolism (Correct answer)
- Increased risk of warfarin-induced hepatotoxicity
Correct answer: Decreased INR due to increased warfarin metabolism
CYP3A4 induction by rifampicin accelerates warfarin metabolism, reducing plasma warfarin levels and anticoagulant effect, leading to a sub-therapeutic INR.
Question 2: Fluoxetine inhibits CYP2D6. A patient taking fluoxetine is prescribed codeine for pain. What is the expected pharmacological outcome?
- Enhanced analgesic effect due to more morphine conversion
- Reduced analgesic effect due to impaired conversion of codeine to morphine (Correct answer)
- No change as codeine does not rely on CYP2D6
- Increased codeine toxicity due to reduced renal clearance
Correct answer: Reduced analgesic effect due to impaired conversion of codeine to morphine
Codeine requires CYP2D6-mediated conversion to morphine for its analgesic effect; CYP2D6 inhibition by fluoxetine reduces morphine production, diminishing analgesia.
Question 3: Amiodarone inhibits CYP2C9. A patient stabilised on warfarin starts amiodarone. What monitoring and action is required?
- No monitoring needed as the interaction is not clinically significant
- Increase warfarin dose to compensate for reduced absorption
- Reduce warfarin dose and increase INR monitoring frequency (Correct answer)
- Switch to aspirin to avoid the interaction
Correct answer: Reduce warfarin dose and increase INR monitoring frequency
Amiodarone's CYP2C9 inhibition increases warfarin plasma levels, raising bleeding risk; warfarin dose reduction and close INR monitoring are required.
Question 4: Which type of drug interaction describes two drugs producing an effect greater than the sum of their individual effects?
- Additive interaction
- Synergistic (supra-additive) interaction (Correct answer)
- Antagonistic interaction
- Competitive interaction
Correct answer: Synergistic (supra-additive) interaction
A synergistic interaction occurs when combined drug effects exceed the arithmetic sum of individual effects, as seen with some antibiotic combinations.
Question 5: A patient on digoxin is started on erythromycin. Erythromycin inhibits P-glycoprotein (P-gp) intestinal efflux transporter. What is the clinical implication?
- Reduced digoxin absorption and lower plasma levels
- Increased digoxin absorption and risk of toxicity (Correct answer)
- Accelerated digoxin renal excretion
- Reduced digoxin protein binding
Correct answer: Increased digoxin absorption and risk of toxicity
P-glycoprotein normally limits digoxin intestinal absorption; inhibition by erythromycin increases digoxin bioavailability and plasma levels, raising toxicity risk.
Question 6: ACE inhibitors and potassium-sparing diuretics (e.g., spironolactone) prescribed together risk which clinically dangerous interaction?
- Pharmacokinetic — reduced renal clearance of ACE inhibitor
- Pharmacodynamic — additive hyperkalemia (Correct answer)
- Pharmacokinetic — enzyme inhibition of both drugs
- Pharmacodynamic — additive hypotension only
Correct answer: Pharmacodynamic — additive hyperkalemia
Both ACE inhibitors (reduce aldosterone) and potassium-sparing diuretics (block aldosterone) independently raise serum potassium, producing additive hyperkalemia when combined.
Question 7: Grapefruit juice inhibits intestinal CYP3A4. A patient drinks grapefruit juice with their simvastatin. What is the expected effect?
- Decreased simvastatin bioavailability and reduced efficacy
- Increased simvastatin bioavailability and increased risk of myopathy (Correct answer)
- No clinically significant effect on simvastatin levels
- Accelerated simvastatin hepatic metabolism
Correct answer: Increased simvastatin bioavailability and increased risk of myopathy
Grapefruit juice inhibits intestinal CYP3A4 via furanocoumarins, reducing simvastatin first-pass metabolism and significantly increasing plasma levels and myopathy risk.
PSA Pharmacology Principles 3
Rifampicin is a potent inducer of CYP3A4.
A patient on long-term warfarin starts rifampicin for tuberculosis.
What is the most likely clinical consequence?