PSA Drug Interactions 3 — Questions and Answers
Question 1: A patient on ramipril is prescribed spironolactone for heart failure. What electrolyte abnormality is the primary concern?
- Hypokalemia from combined natriuresis
- Hyperkalemia from dual potassium-retaining mechanisms (Correct answer)
- Hyponatremia from combined diuretic effects
- Hypercalcemia from altered calcium reabsorption
Correct answer: Hyperkalemia from dual potassium-retaining mechanisms
Both ACE inhibitors and potassium-sparing diuretics independently reduce renal potassium excretion; their combination creates additive hyperkalemia risk, particularly in those with renal impairment.
Question 2: Which drug combination carries the highest risk of serotonin syndrome?
- SSRI with a beta-blocker
- SSRI with a proton pump inhibitor
- SSRI with a monoamine oxidase inhibitor (Correct answer)
- SSRI with a thiazide diuretic
Correct answer: SSRI with a monoamine oxidase inhibitor
MAOIs prevent serotonin degradation while SSRIs block its reuptake; together they cause massive serotonergic excess, presenting as hyperthermia, tremor, clonus, and autonomic instability.
Question 3: A patient on digoxin 125 mcg daily starts amiodarone for atrial fibrillation. Which mechanism best explains the increased digoxin toxicity risk?
- Amiodarone induces renal CYP3A4, producing toxic digoxin metabolites
- Amiodarone displaces digoxin from tissue binding sites, increasing free levels
- Amiodarone inhibits P-glycoprotein, reducing renal and biliary digoxin elimination (Correct answer)
- Pharmacodynamic synergism at the Na+/K+-ATPase pump doubles the inotropic effect
Correct answer: Amiodarone inhibits P-glycoprotein, reducing renal and biliary digoxin elimination
Amiodarone inhibits P-glycoprotein-mediated secretion of digoxin in the kidney and bile duct, causing plasma digoxin concentrations to approximately double.
Question 4: Which drug combination constitutes the renal 'triple whammy' associated with acute kidney injury?
- NSAIDs + ACE inhibitors + potassium-sparing diuretics
- NSAIDs + ACE inhibitors (or ARBs) + loop or thiazide diuretics (Correct answer)
- Aspirin + statins + beta-blockers
- Metformin + ACE inhibitors + loop diuretics
Correct answer: NSAIDs + ACE inhibitors (or ARBs) + loop or thiazide diuretics
NSAIDs reduce efferent arteriolar dilation, ACE inhibitors blunt angiotensin II-mediated efferent constriction, and diuretics cause hypovolemia — together these mechanisms collapse glomerular filtration pressure.
Question 5: Which drug combination creates the greatest additive risk of QT prolongation and torsades de pointes?
- Metformin and linagliptin
- Amoxicillin and ibuprofen
- Amiodarone and sotalol (Correct answer)
- Atorvastatin and ezetimibe
Correct answer: Amiodarone and sotalol
Both amiodarone and sotalol independently prolong the cardiac action potential by blocking potassium channels; combining them markedly amplifies QT prolongation and arrhythmia risk.
Question 6: Naloxone reverses opioid-induced respiratory depression via which interaction mechanism?
- Pharmacokinetic inhibition of CYP3A4-mediated opioid metabolism
- Pharmaceutical incompatibility forming inactive opioid-naloxone complexes in blood
- Competitive pharmacodynamic antagonism at mu-opioid receptors (Correct answer)
- Allosteric modulation of the kappa-opioid receptor reducing opioid binding affinity
Correct answer: Competitive pharmacodynamic antagonism at mu-opioid receptors
Naloxone has very high affinity for mu-opioid receptors and rapidly displaces opioid agonists by competitive antagonism, reversing analgesia, sedation, and respiratory depression.
Question 7: A patient prescribed an opioid analgesic is also taking a benzodiazepine for anxiety. The most dangerous pharmacodynamic interaction produces:
- Serotonin syndrome from combined monoamine effects
- Neuroleptic malignant syndrome from dopaminergic disruption
- QT prolongation from additive ion channel blockade
- Additive CNS and respiratory depression with risk of fatal apnea (Correct answer)
Correct answer: Additive CNS and respiratory depression with risk of fatal apnea
Opioids and benzodiazepines both suppress central respiratory drive through distinct but complementary mechanisms; their combination multiplicatively increases the risk of fatal respiratory arrest.
PSA Drug Interactions 3
A patient on ramipril is prescribed spironolactone for heart failure.
What electrolyte abnormality is the primary concern?