PSA Adverse Drug Reactions 3 — Questions and Answers
Question 1: A patient develops a persistent dry cough 3 weeks after starting ramipril for hypertension. What is the most appropriate management?
- Add a cough suppressant and continue ramipril
- Switch to an angiotensin receptor blocker (Correct answer)
- Reduce the ramipril dose by half
- Switch to a beta-blocker
Correct answer: Switch to an angiotensin receptor blocker
ACE inhibitor-induced cough is caused by bradykinin accumulation and does not resolve with dose reduction; switching to an ARB avoids bradykinin-related effects entirely.
Question 2: Metformin should be withheld in patients with an eGFR below which threshold due to the risk of lactic acidosis?
- 60 mL/min/1.73m²
- 45 mL/min/1.73m²
- 30 mL/min/1.73m² (Correct answer)
- 15 mL/min/1.73m²
Correct answer: 30 mL/min/1.73m²
Metformin is contraindicated when eGFR falls below 30 mL/min/1.73m² because impaired renal clearance leads to drug accumulation and risk of potentially fatal lactic acidosis.
Question 3: A patient on simvastatin 40 mg starts clarithromycin for a chest infection and develops severe myalgia with dark urine. What is the most likely mechanism?
- Clarithromycin directly damages skeletal muscle
- Clarithromycin inhibits CYP3A4, raising simvastatin plasma levels (Correct answer)
- The simvastatin dose was independently too high
- Clarithromycin induces CYP3A4, increasing statin conversion to toxic metabolites
Correct answer: Clarithromycin inhibits CYP3A4, raising simvastatin plasma levels
Clarithromycin is a potent CYP3A4 inhibitor that markedly increases simvastatin exposure, precipitating statin-induced myopathy and potentially rhabdomyolysis.
Question 4: NSAIDs precipitate acute kidney injury primarily through which mechanism?
- Direct tubular cytotoxicity
- Inhibition of prostaglandin-mediated afferent arteriolar vasodilation (Correct answer)
- Immune complex-mediated glomerulonephritis
- Increased uric acid precipitation in renal tubules
Correct answer: Inhibition of prostaglandin-mediated afferent arteriolar vasodilation
NSAIDs inhibit prostaglandin synthesis, abolishing the afferent arteriolar vasodilation that maintains glomerular filtration rate when renal perfusion pressure is reduced.
Question 5: A patient on warfarin has their INR rise from 2.5 to 5.8 after starting trimethoprim for a UTI. What is the primary mechanism of this interaction?
- Trimethoprim displaces warfarin from plasma protein binding sites
- Trimethoprim inhibits CYP2C9, reducing S-warfarin metabolism (Correct answer)
- Trimethoprim increases gastrointestinal absorption of warfarin
- Trimethoprim inhibits intestinal vitamin K absorption
Correct answer: Trimethoprim inhibits CYP2C9, reducing S-warfarin metabolism
Trimethoprim inhibits CYP2C9, the primary enzyme metabolizing the more potent S-warfarin enantiomer, leading to drug accumulation and supratherapeutic anticoagulation.
Question 6: Which monitoring parameter is most important when prescribing aminoglycosides to prevent nephrotoxicity and ototoxicity?
- Peak serum levels alone
- Trough serum levels and renal function (Correct answer)
- Liver function tests
- Full blood count weekly
Correct answer: Trough serum levels and renal function
Aminoglycoside toxicity is concentration-time dependent, with sustained elevated trough levels predicting nephrotoxicity and ototoxicity; dose intervals are adjusted based on trough and eGFR.
Question 7: Clozapine requires mandatory full blood count monitoring primarily because of which serious adverse drug reaction?
- Severe thrombocytopenia
- Agranulocytosis (Correct answer)
- Aplastic anaemia
- Haemolytic anaemia
Correct answer: Agranulocytosis
Clozapine causes agranulocytosis in approximately 1% of patients, necessitating weekly FBC monitoring for the first 18 weeks then at minimum every 4 weeks thereafter.
PSA Adverse Drug Reactions 3
A patient develops a persistent dry cough 3 weeks after starting ramipril for hypertension.
What is the most appropriate management?