CAOP Drug Interactions and Contraindications 1 — Questions and Answers
Question 1: A patient on warfarin is prescribed ibuprofen for pain. What is the primary concern with this combination?
- Reduced anticoagulant effect of warfarin
- Increased bleeding risk due to additive anticoagulation and GI mucosal damage (Correct answer)
- Ibuprofen accelerates warfarin metabolism via CYP2C9 induction
- Warfarin increases ibuprofen plasma levels causing toxicity
Correct answer: Increased bleeding risk due to additive anticoagulation and GI mucosal damage
NSAIDs like ibuprofen inhibit platelet aggregation and damage the GI mucosa, and can also displace warfarin from protein binding, increasing bleeding risk.
Question 2: Which combination of antihypertensive agents poses the greatest risk of dangerous hyperkalaemia?
- ACE inhibitor + calcium channel blocker
- ACE inhibitor + potassium-sparing diuretic (Correct answer)
- Beta-blocker + thiazide diuretic
- ARB + calcium channel blocker
Correct answer: ACE inhibitor + potassium-sparing diuretic
ACE inhibitors reduce aldosterone secretion and potassium excretion; combining with potassium-sparing diuretics (e.g., spironolactone) can cause life-threatening hyperkalaemia.
Question 3: A patient taking a monoamine oxidase inhibitor (MAOI) is started on sertraline. What potentially fatal interaction can occur?
- Hypertensive crisis due to norepinephrine accumulation
- Serotonin syndrome due to excessive serotonergic activity (Correct answer)
- Neuroleptic malignant syndrome due to dopamine blockade
- Severe anticholinergic toxidrome
Correct answer: Serotonin syndrome due to excessive serotonergic activity
Combining MAOIs with SSRIs can cause serotonin syndrome, a life-threatening condition characterised by hyperthermia, agitation, tremor, and clonus.
Question 4: Amiodarone is added to a patient's regimen that includes digoxin. What is the expected pharmacokinetic outcome?
- Amiodarone induces P-glycoprotein, reducing digoxin levels
- Amiodarone inhibits P-glycoprotein and CYP, increasing digoxin plasma levels (Correct answer)
- Digoxin inhibits amiodarone metabolism, causing amiodarone toxicity
- No clinically significant interaction between these two agents
Correct answer: Amiodarone inhibits P-glycoprotein and CYP, increasing digoxin plasma levels
Amiodarone inhibits P-glycoprotein-mediated renal excretion of digoxin and reduces its volume of distribution, typically doubling digoxin levels and requiring a dose reduction.
Question 5: Metformin should be withheld before and after administration of iodinated contrast media primarily because of the risk of:
- Hypoglycaemia due to altered carbohydrate metabolism
- Contrast-induced nephropathy leading to metformin accumulation and lactic acidosis (Correct answer)
- Allergic cross-reaction between metformin and iodine
- QT prolongation due to the combination
Correct answer: Contrast-induced nephropathy leading to metformin accumulation and lactic acidosis
Contrast media can impair renal function; reduced renal clearance allows metformin to accumulate, increasing the risk of potentially fatal lactic acidosis.
Question 6: Concomitant use of a statin and gemfibrozil significantly increases the risk of:
- Hepatotoxicity leading to fulminant hepatic failure
- Rhabdomyolysis due to increased statin plasma concentrations (Correct answer)
- Severe hypoglycaemia by inhibiting gluconeogenesis
- Prolonged QT interval and torsades de pointes
Correct answer: Rhabdomyolysis due to increased statin plasma concentrations
Gemfibrozil inhibits CYP2C8 and OATP1B1, markedly increasing statin exposure and the risk of myopathy and rhabdomyolysis, particularly with cerivastatin (withdrawn) and simvastatin.
Question 7: Which of the following medications is most commonly associated with QT interval prolongation and torsades de pointes when combined with other QT-prolonging agents?
- Metoprolol
- Domperidone (Correct answer)
- Omeprazole
- Metformin
Correct answer: Domperidone
Domperidone blocks hERG potassium channels, prolonging the QT interval; combining it with other QT-prolonging drugs (e.g., azithromycin, antifungals) markedly increases the risk of torsades de pointes.
CAOP Drug Interactions and Contraindications 1
A patient on warfarin is prescribed ibuprofen for pain.
What is the primary concern with this combination?