Potassium-sparing diuretics, especially spironolactone, are essential topics for B. Pharm students. Spironolactone is an aldosterone antagonist acting at the late distal tubule and collecting duct to reduce sodium reabsorption and prevent potassium loss. Understanding spironolactone’s mechanism of action, pharmacokinetics (prodrug with active metabolite canrenone), therapeutic uses (heart failure, cirrhosis with ascites, resistant hypertension), dose considerations, adverse effects (hyperkalemia, gynecomastia, menstrual irregularities), contraindications and drug interactions (ACE inhibitors, ARBs, NSAIDs) is crucial for safe pharmacotherapy. Focus on monitoring serum potassium and renal function during therapy. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which of the following best describes the primary mechanism of action of spironolactone?
- Blockade of epithelial sodium channels (ENaC) in the collecting duct
- Inhibition of carbonic anhydrase in the proximal tubule
- Aldosterone (mineralocorticoid) receptor antagonism in the distal nephron
- Inhibition of the Na+-K+-2Cl- cotransporter in the thick ascending limb
Correct Answer: Aldosterone (mineralocorticoid) receptor antagonism in the distal nephron
Q2. At which renal site does spironolactone principally exert its effect?
- Proximal convoluted tubule
- Thick ascending limb of Henle
- Late distal tubule and collecting duct (principal cells)
- Glomerulus
Correct Answer: Late distal tubule and collecting duct (principal cells)
Q3. Spironolactone can be classified pharmacologically as:
- A loop diuretic
- An aldosterone receptor antagonist (potassium-sparing diuretic)
- A thiazide diuretic
- A carbonic anhydrase inhibitor
Correct Answer: An aldosterone receptor antagonist (potassium-sparing diuretic)
Q4. Which active metabolite is most closely associated with spironolactone’s diuretic activity?
- Canrenone
- Furosemide
- Triamterene
- Amiloride
Correct Answer: Canrenone
Q5. A major clinical indication for spironolactone is:
- Acute pulmonary edema as first-line monotherapy
- Management of ascites due to liver cirrhosis
- Primary treatment for hyperkalemia
- Primary therapy for nephrogenic diabetes insipidus
Correct Answer: Management of ascites due to liver cirrhosis
Q6. Which adverse effect is characteristically linked to spironolactone’s antiandrogenic activity?
- Hypokalemia
- Gynecomastia and sexual dysfunction
- Ototoxicity
- Hyperglycemia
Correct Answer: Gynecomastia and sexual dysfunction
Q7. Combining spironolactone with which of the following increases the greatest risk of hyperkalemia?
- Loop diuretics (e.g., furosemide)
- Thiazide diuretics (e.g., hydrochlorothiazide)
- ACE inhibitors (e.g., lisinopril)
- Calcium channel blockers (e.g., amlodipine)
Correct Answer: ACE inhibitors (e.g., lisinopril)
Q8. Which laboratory tests should be monitored regularly when a patient is taking spironolactone?
- Serum glucose and lipid profile
- Serum potassium and renal function (creatinine/BUN)
- Liver enzymes only
- Thyroid function tests
Correct Answer: Serum potassium and renal function (creatinine/BUN)
Q9. Compared with spironolactone, eplerenone is best described as:
- A nonsteroidal loop diuretic with stronger antiandrogen effects
- A selective mineralocorticoid receptor antagonist with fewer endocrine side effects
- An ENaC blocker with higher risk of gynecomastia
- A thiazide-like diuretic used for edema
Correct Answer: A selective mineralocorticoid receptor antagonist with fewer endocrine side effects
Q10. Which ECG change is an early sign of spironolactone-induced hyperkalemia?
- Peaked T waves
- U waves
- Delta waves
- Prolonged QTc only
Correct Answer: Peaked T waves
Q11. Which of the following is a contraindication to spironolactone therapy?
- Hypokalemia
- Pregnancy due to potential antiandrogenic fetal effects
- Essential hypertension responsive to thiazides
- Osteoporosis
Correct Answer: Pregnancy due to potential antiandrogenic fetal effects
Q12. The diuretic effect of spironolactone is best characterized as:
- Rapid onset and short duration like furosemide
- Slow onset with effect dependent on synthesis blockade of aldosterone-induced proteins
- Immediate ENaC blockade within minutes
- Acting predominantly in the proximal tubule
Correct Answer: Slow onset with effect dependent on synthesis blockade of aldosterone-induced proteins
Q13. Which dosing range is commonly used for oral spironolactone in adults for heart failure or edema?
- 25–100 mg per day
- 500–1000 mg per day
- 0.5–2 mg per day
- 200–400 mg per day only
Correct Answer: 25–100 mg per day
Q14. Spironolactone’s pharmacologic classification as a steroidal compound explains which property?
- Its action as an ACE inhibitor
- Its antiandrogenic and progestogenic effects leading to endocrine adverse effects
- Its renal excretion unchanged exclusively
- Its ability to block carbonic anhydrase
Correct Answer: Its antiandrogenic and progestogenic effects leading to endocrine adverse effects
Q15. Which of the following clinical uses of spironolactone is supported by strong evidence?
- Primary treatment of nephrotic syndrome proteinuria
- Reduction of morbidity and mortality in selected patients with chronic heart failure
- Treatment of acute hypertensive emergency as first-line
- Cure for polycystic kidney disease
Correct Answer: Reduction of morbidity and mortality in selected patients with chronic heart failure
Q16. A student asks why spironolactone causes hyperkalemia. The best explanation is:
- It increases aldosterone production, causing potassium retention
- It blocks aldosterone receptors, reducing sodium reabsorption and decreasing potassium excretion
- It enhances distal sodium reabsorption and increases potassium secretion
- It directly binds potassium ions in the tubule lumen
Correct Answer: It blocks aldosterone receptors, reducing sodium reabsorption and decreasing potassium excretion
Q17. Which drug interaction may reduce the antihypertensive and diuretic efficacy of spironolactone?
- Concurrent use of NSAIDs due to reduced renal prostaglandin-mediated diuresis
- Concurrent use of loop diuretics
- Concurrent use of potassium supplements
- Concurrent use of eplerenone
Correct Answer: Concurrent use of NSAIDs due to reduced renal prostaglandin-mediated diuresis
Q18. In a patient with renal impairment, spironolactone dosage should be adjusted because:
- It is cleared entirely by the lungs
- Renal impairment increases risk of hyperkalemia due to reduced potassium excretion
- It causes profound hypokalemia in renal failure
- It is ineffective in renal impairment so doses should be increased
Correct Answer: Renal impairment increases risk of hyperkalemia due to reduced potassium excretion
Q19. Which adverse endocrine effect is common in female patients taking spironolactone?
- Hirsutism
- Menstrual irregularities and breast tenderness
- Hyperthyroidism
- Increased ovarian estrogen production
Correct Answer: Menstrual irregularities and breast tenderness
Q20. For pharmacokinetic understanding: spironolactone is best described as:
- An active drug excreted unchanged with no metabolites
- A prodrug metabolized in the liver to active metabolites such as canrenone
- A peptide drug degraded in the GI tract with no oral availability
- Excreted primarily in bile as unchanged compound only
Correct Answer: A prodrug metabolized in the liver to active metabolites such as canrenone
Q21. Which patient population requires extra caution or avoidance of spironolactone?
- Patients with hypokalemia and metabolic alkalosis
- Pregnant women and those with baseline hyperkalemia or severe renal impairment
- Young adults with no comorbidities
- Patients with chronic cough on ACE inhibitors
Correct Answer: Pregnant women and those with baseline hyperkalemia or severe renal impairment
Q22. When used to treat resistant hypertension, spironolactone is often effective because:
- It acts as a potent vasodilator independent of aldosterone
- Aldosterone-mediated sodium retention often contributes to resistant hypertension and spironolactone blocks this effect
- It increases cardiac output significantly
- It acts predominantly in the loop of Henle to remove large fluid volumes
Correct Answer: Aldosterone-mediated sodium retention often contributes to resistant hypertension and spironolactone blocks this effect
Q23. Which of the following is a distinguishing pharmacological difference between spironolactone and amiloride?
- Spironolactone antagonizes aldosterone receptors, whereas amiloride blocks ENaC channels directly
- Both are ACE inhibitors with similar structures
- Amiloride is steroidal and causes gynecomastia, spironolactone does not
- Spironolactone is an ENaC blocker and amiloride is an aldosterone antagonist
Correct Answer: Spironolactone antagonizes aldosterone receptors, whereas amiloride blocks ENaC channels directly
Q24. In the management of cirrhotic ascites, spironolactone is typically combined with which agent for synergistic effect?
- Loop diuretic (e.g., furosemide)
- Beta-blocker (e.g., propranolol)
- ACE inhibitor (e.g., enalapril)
- Calcium supplement
Correct Answer: Loop diuretic (e.g., furosemide)
Q25. Which monitoring parameter helps detect early renal adverse effects during spironolactone therapy?
- Daily weight only
- Serum creatinine and estimated glomerular filtration rate (eGFR)
- Chest X-ray
- Fasting blood glucose
Correct Answer: Serum creatinine and estimated glomerular filtration rate (eGFR)
Q26. Which statement about spironolactone’s effect on acid-base balance is most accurate?
- It commonly causes severe metabolic alkalosis
- It may produce mild metabolic acidosis in some patients due to decreased H+ secretion
- It causes respiratory acidosis by depressing respiration
- It has no effect on acid-base balance ever
Correct Answer: It may produce mild metabolic acidosis in some patients due to decreased H+ secretion
Q27. Regarding therapeutic onset and duration, spironolactone typically:
- Has an immediate diuretic effect within minutes and lasts 2 hours
- Requires several days for maximal effect due to active metabolites and gene expression changes
- Is ineffective when given orally
- Works only when administered intravenously
Correct Answer: Requires several days for maximal effect due to active metabolites and gene expression changes
Q28. A B. Pharm student asks which adverse effect is reversible on stopping spironolactone. The best example is:
- Permanent gynecomastia in all patients
- Hyperkalemia that always persists after stopping
- Menstrual irregularities and breast tenderness which often resolve after discontinuation
- Renal cortical necrosis that reverses
Correct Answer: Menstrual irregularities and breast tenderness which often resolve after discontinuation
Q29. Which statement regarding spironolactone and potassium supplementation is correct?
- Potassium supplements are routinely recommended with spironolactone
- Potassium supplements should be avoided or used cautiously because of hyperkalemia risk
- Spironolactone causes hypokalemia, so supplements are mandatory
- Potassium supplements have no interaction with spironolactone
Correct Answer: Potassium supplements should be avoided or used cautiously because of hyperkalemia risk
Q30. In pharmaceutical education, why is it important to understand spironolactone’s drug interactions?
- Because spironolactone has no clinically significant interactions
- To prevent adverse outcomes like severe hyperkalemia and to optimize combined therapy with ACE inhibitors, ARBs, NSAIDs, and other agents
- Only to decide pill color and packaging
- Because interactions are only theoretical and not seen clinically
Correct Answer: To prevent adverse outcomes like severe hyperkalemia and to optimize combined therapy with ACE inhibitors, ARBs, NSAIDs, and other agents
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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