SPEX SPEX Pharmacology 4 — Questions and Answers
Question 1: A patient on warfarin begins taking trimethoprim-sulfamethoxazole for a UTI. What is the most likely effect on warfarin's anticoagulant activity?
- Decreased anticoagulation due to enzyme induction
- Increased anticoagulation due to enzyme inhibition (Correct answer)
- No significant interaction expected
- Decreased anticoagulation due to reduced absorption
Correct answer: Increased anticoagulation due to enzyme inhibition
TMP-SMX inhibits CYP2C9, the primary enzyme metabolizing warfarin's S-enantiomer, leading to elevated INR and increased bleeding risk.
Question 2: Which mechanism best explains tachyphylaxis to nitrate therapy used for angina?
- Downregulation of nitrate receptors
- Depletion of sulfhydryl groups needed for nitric oxide formation (Correct answer)
- Increased hepatic first-pass metabolism
- Development of antibodies against the nitrate molecule
Correct answer: Depletion of sulfhydryl groups needed for nitric oxide formation
Continuous nitrate exposure depletes sulfhydryl (–SH) groups required for conversion to nitric oxide, resulting in diminished vasodilatory response.
Question 3: A 68-year-old with stage 3 CKD is prescribed metformin. Which concern is most clinically relevant?
- Severe hypoglycemia
- Lactic acidosis due to reduced renal clearance (Correct answer)
- QT prolongation
- Hepatotoxicity from active metabolite accumulation
Correct answer: Lactic acidosis due to reduced renal clearance
Metformin is renally cleared, and accumulation in CKD raises plasma levels that promote anaerobic metabolism and life-threatening lactic acidosis.
Question 4: Which pharmacokinetic parameter best predicts the risk of drug accumulation in a patient receiving multiple doses?
- Volume of distribution
- Bioavailability
- Half-life (Correct answer)
- Protein binding percentage
Correct answer: Half-life
Half-life determines the time to reach steady state and the extent of accumulation; drugs with long half-lives accumulate more with repeated dosing.
Question 5: A physician prescribes fluconazole to a patient already taking cisapride. Why is this combination contraindicated?
- Fluconazole reduces cisapride absorption
- Fluconazole inhibits CYP3A4, raising cisapride levels and risking torsades de pointes (Correct answer)
- Cisapride induces fluconazole metabolism
- Combined use causes severe hepatotoxicity
Correct answer: Fluconazole inhibits CYP3A4, raising cisapride levels and risking torsades de pointes
Fluconazole is a potent CYP3A4 inhibitor; cisapride relies on CYP3A4 for clearance, so co-administration elevates cisapride concentrations and prolongs QT, potentially causing fatal arrhythmia.
Question 6: The concept of 'therapeutic index' is best described as:
- The ratio of the effective dose to the lethal dose (TD50/ED50)
- The ratio of the toxic dose to the effective dose (TD50/ED50) (Correct answer)
- The minimum effective concentration divided by the maximum tolerated concentration
- The dose required to produce a response in 50% of the population
Correct answer: The ratio of the toxic dose to the effective dose (TD50/ED50)
Therapeutic index = TD50/ED50; a higher value indicates a safer drug with a wider margin between therapeutic and toxic doses.
Question 7: Which drug class directly inhibits the Na+/K+-ATPase pump to exert its pharmacological effect?
- Beta-blockers
- ACE inhibitors
- Cardiac glycosides (Correct answer)
- Loop diuretics
Correct answer: Cardiac glycosides
Cardiac glycosides (e.g., digoxin) inhibit Na+/K+-ATPase, increasing intracellular sodium, which indirectly raises intracellular calcium and enhances myocardial contractility.
SPEX SPEX Pharmacology 4
A patient on warfarin begins taking trimethoprim-sulfamethoxazole for a UTI.
What is the most likely effect on warfarin's anticoagulant activity?