MCQ Quiz: Pharmacology of Aldosterone Antagonists

Aldosterone antagonists, also known as Mineralocorticoid Receptor Antagonists (MRAs), are a vital class of drugs in cardiovascular and renal pharmacotherapy. They play a crucial role in managing conditions such as heart failure, hypertension (particularly resistant hypertension), and primary hyperaldosteronism by counteracting the deleterious effects of aldosterone. For PharmD students, a comprehensive understanding of the pharmacology of these agents—including their mechanisms of action at the mineralocorticoid receptor, pharmacokinetic profiles, therapeutic benefits, potential adverse effects like hyperkalemia, and important drug interactions—is essential for optimizing patient care and ensuring medication safety. This MCQ quiz will test your knowledge on the pharmacological principles governing aldosterone antagonists.

1. Aldosterone antagonists exert their primary pharmacological effect by competitively blocking the binding of aldosterone to which receptor?

• A. Angiotensin II AT1 receptor
• B. Beta-1 adrenergic receptor
• C. Mineralocorticoid Receptor (MR)
• D. Glucocorticoid receptor

Answer: C. Mineralocorticoid Receptor (MR)

2. The physiological effects of aldosterone binding to mineralocorticoid receptors in the renal distal tubules and collecting ducts include:

• A. Increased sodium and water excretion, and potassium retention
• B. Increased sodium and water retention, and potassium and hydrogen ion excretion
• C. Vasodilation and decreased blood pressure
• D. Inhibition of cardiac fibrosis

Answer: B. Increased sodium and water retention, and potassium and hydrogen ion excretion

3. Spironolactone is classified as a(n):

• A. Selective aldosterone antagonist
• B. Non-selective aldosterone antagonist with activity at androgen and progesterone receptors
• C. Loop diuretic
• D. ACE inhibitor

Answer: B. Non-selective aldosterone antagonist with activity at androgen and progesterone receptors

4. Eplerenone differs from spironolactone in that eplerenone is:

• A. A more potent diuretic at equivalent doses.
• B. A non-selective aldosterone antagonist.
• C. A more selective aldosterone antagonist with lower affinity for androgen and progesterone receptors.
• D. Administered intravenously only.

Answer: C. A more selective aldosterone antagonist with lower affinity for androgen and progesterone receptors.

5. Finerenone is a newer aldosterone antagonist characterized by its:

• A. Steroidal chemical structure similar to spironolactone
• B. Non-steroidal chemical structure and selective mineralocorticoid receptor antagonism
• C. Primary action on beta-adrenergic receptors
• D. Requirement for hepatic activation to an active metabolite

Answer: B. Non-steroidal chemical structure and selective mineralocorticoid receptor antagonism

6. The primary therapeutic benefit of aldosterone antagonists in patients with Heart Failure with reduced Ejection Fraction (HFrEF) is:

• A. Primarily symptomatic relief of acute congestion
• B. Reduction in morbidity and mortality by attenuating adverse cardiac remodeling, fibrosis, and neurohormonal dysregulation
• C. Significant increase in ejection fraction within days of initiation
• D. Prevention of atrial fibrillation only

Answer: B. Reduction in morbidity and mortality by attenuating adverse cardiac remodeling, fibrosis, and neurohormonal dysregulation

7. Which of the following is a common and potentially life-threatening adverse effect of aldosterone antagonist therapy?

• A. Hypokalemia
• B. Hyperkalemia
• C. Hyponatremia
• D. Hypocalcemia

Answer: B. Hyperkalemia

8. Gynecomastia and menstrual irregularities are adverse effects more commonly associated with which aldosterone antagonist due to its non-selectivity?

• A. Eplerenone
• B. Finerenone
• C. Spironolactone
• D. All are equally likely to cause these effects.

Answer: C. Spironolactone

9. Which laboratory parameters must be closely monitored before and during therapy with aldosterone antagonists?

• A. Liver function tests and lipid panel
• B. Serum potassium and renal function (serum creatinine and eGFR)
• C. Complete blood count and coagulation profile
• D. Serum uric acid and glucose levels

Answer: B. Serum potassium and renal function (serum creatinine and eGFR)

10. Aldosterone antagonists are often used in the management of resistant hypertension, which is defined as blood pressure remaining above goal despite treatment with:

• A. One antihypertensive agent
• B. Two antihypertensive agents from different classes
• C. Three or more antihypertensive agents from different classes, ideally including a diuretic, at optimal doses
• D. Only a beta-blocker and an ACE inhibitor

Answer: C. Three or more antihypertensive agents from different classes, ideally including a diuretic, at optimal doses

11. Spironolactone is metabolized in the liver to active metabolites, including:

• A. Eplerenone
• B. Canrenone
• C. Finerenone
• D. Aldosterone itself

Answer: B. Canrenone

12. Eplerenone is a substrate for which major cytochrome P450 enzyme, leading to potential drug interactions?

• A. CYP2D6
• B. CYP2C9
• C. CYP3A4
• D. CYP1A2

Answer: C. CYP3A4

13. Co-administration of aldosterone antagonists with which of the following drug classes significantly increases the risk of severe hyperkalemia?

• A. Loop diuretics
• B. ACE inhibitors, ARBs, or potassium supplements
• C. Calcium channel blockers
• D. Beta-blockers

Answer: B. ACE inhibitors, ARBs, or potassium supplements

14. In which of the following conditions is the use of aldosterone antagonists generally contraindicated or requires extreme caution?

• A. Mild hypertension
• B. Significant pre-existing hyperkalemia (e.g., K+ > 5.0-5.5 mEq/L) or severe renal impairment
• C. Ischemic heart disease
• D. Dyslipidemia

Answer: B. Significant pre-existing hyperkalemia (e.g., K+ > 5.0-5.5 mEq/L) or severe renal impairment

15. Finerenone has shown benefits in patients with chronic kidney disease (CKD) and type 2 diabetes by:

• A. Primarily lowering blood glucose.
• B. Reducing the risk of CKD progression and cardiovascular events.
• C. Significantly increasing glomerular filtration rate in all patients.
• D. Promoting weight loss.

Answer: B. Reducing the risk of CKD progression and cardiovascular events.

16. The diuretic effect of aldosterone antagonists is generally considered to be:

• A. Very potent and rapid in onset, similar to loop diuretics.
• B. Relatively weak, as they act on the distal nephron where only a small fraction of sodium reabsorption occurs.
• C. Most effective when serum potassium is low.
• D. Independent of aldosterone levels.

Answer: B. Relatively weak, as they act on the distal nephron where only a small fraction of sodium reabsorption occurs.

17. Besides the kidneys, mineralocorticoid receptors are also found in which other tissues where aldosterone can exert detrimental effects in HF?

• A. Lungs and skeletal muscle only
• B. Heart, blood vessels, and brain
• C. Liver and pancreas only
• D. Adipose tissue exclusively

Answer: B. Heart, blood vessels, and brain

18. What is the primary mechanism by which aldosterone contributes to cardiac fibrosis?

• A. By directly inhibiting collagen synthesis
• B. By promoting inflammation and stimulating fibroblast activity and collagen deposition
• C. By causing vasodilation and reducing wall stress
• D. By increasing nitric oxide availability

Answer: B. By promoting inflammation and stimulating fibroblast activity and collagen deposition

19. Which landmark clinical trial first demonstrated a significant mortality benefit with spironolactone in patients with severe HFrEF already on ACE inhibitors and diuretics?

• A. EPHESUS
• B. RALES (Randomized Aldactone Evaluation Study)
• C. EMPHASIS-HF
• D. PARADIGM-HF

Answer: B. RALES (Randomized Aldactone Evaluation Study)

20. The EPHESUS trial demonstrated the benefit of eplerenone in which specific patient population post-myocardial infarction?

• A. Patients with normal LVEF and no HF symptoms
• B. Patients with LVEF ≤ 40% and either symptomatic HF or diabetes mellitus
• C. All patients post-MI regardless of LVEF or symptoms
• D. Patients with severe renal impairment post-MI

Answer: B. Patients with LVEF ≤ 40% and either symptomatic HF or diabetes mellitus

21. A patient on spironolactone complains of painful breast enlargement. This is most likely due to spironolactone’s action on:

• A. Mineralocorticoid receptors in breast tissue
• B. Androgen and/or progesterone receptors
• C. Estrogen receptors directly
• D. Dopamine receptors

Answer: B. Androgen and/or progesterone receptors

22. When initiating an aldosterone antagonist in a HFrEF patient already on an ACE inhibitor or ARB, the starting dose should generally be:

• A. High, to achieve rapid therapeutic effects
• B. Low, with careful upward titration based on potassium levels, renal function, and tolerance
• C. The same for all patients regardless of other medications
• D. Administered intravenously

Answer: B. Low, with careful upward titration based on potassium levels, renal function, and tolerance

23. What is the primary indication for aldosterone antagonists in the management of primary hyperaldosteronism (Conn’s syndrome)?

• A. To reduce blood glucose levels
• B. To control hypertension and hypokalemia by blocking aldosterone’s effects
• C. To increase aldosterone production
• D. To prevent cardiac arrhythmias only

Answer: B. To control hypertension and hypokalemia by blocking aldosterone’s effects

24. Strong inhibitors of CYP3A4 (e.g., ketoconazole, clarithromycin) can significantly increase the plasma concentrations and risk of adverse effects of which aldosterone antagonist?

• A. Spironolactone
• B. Eplerenone
• C. Canrenone
• D. Finerenone (also a CYP3A4 substrate, but eplerenone is a classic example for this interaction)

Answer: B. Eplerenone

25. What is the mechanism behind NSAID-induced increased risk of hyperkalemia when co-administered with aldosterone antagonists?

• A. NSAIDs directly increase potassium reabsorption.
• B. NSAIDs can impair renal function and reduce renal prostaglandin synthesis, which can decrease potassium excretion and blunt the effects of diuretics.
• C. NSAIDs inhibit the metabolism of aldosterone antagonists.
• D. NSAIDs displace aldosterone from its receptor.

Answer: B. NSAIDs can impair renal function and reduce renal prostaglandin synthesis, which can decrease potassium excretion and blunt the effects of diuretics.

26. The onset of action for the diuretic and blood pressure-lowering effects of spironolactone is typically:

• A. Very rapid (within hours)
• B. Gradual, taking several days to a few weeks to become fully manifest
• C. Immediate upon IV administration
• D. Dependent on dietary sodium intake only

Answer: B. Gradual, taking several days to a few weeks to become fully manifest

27. Finerenone is described as a “non-steroidal” MRA. This structural difference from spironolactone and eplerenone may contribute to:

• A. Increased binding to androgen receptors.
• B. A different binding mode to the MR and potentially a different profile of gene regulation, possibly leading to different renal and cardiovascular effects or side effect profiles.
• C. Faster onset of action.
• D. Requirement for metabolic activation.

Answer: B. A different binding mode to the MR and potentially a different profile of gene regulation, possibly leading to different renal and cardiovascular effects or side effect profiles.

28. In patients with HFrEF, aldosterone antagonists are typically added to which background therapies?

• A. Only diuretics
• B. An ACE inhibitor (or ARB or ARNI) and a beta-blocker
• C. Only digoxin
• D. Calcium channel blockers

Answer: B. An ACE inhibitor (or ARB or ARNI) and a beta-blocker

29. What is the effect of aldosterone on endothelial function that is counteracted by MRAs?

• A. It promotes nitric oxide production and vasodilation.
• B. It can cause endothelial dysfunction, reduce nitric oxide availability, and promote vascular inflammation.
• C. It enhances endothelial repair mechanisms.
• D. It has no significant effect on the endothelium.

Answer: B. It can cause endothelial dysfunction, reduce nitric oxide availability, and promote vascular inflammation.

30. Which condition represents an absolute contraindication for initiating spironolactone or eplerenone based on renal function, according to many guidelines?

• A. eGFR > 60 mL/min/1.73m²
• B. eGFR < 30 mL/min/1.73m² or serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women (specific cutoffs can vary)
• C. Mild proteinuria
• D. History of a single kidney stone

Answer: B. eGFR < 30 mL/min/1.73m² or serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women (specific cutoffs can vary)

31. How do aldosterone antagonists affect magnesium levels?

• A. They cause significant hypermagnesemia.
• B. They can promote magnesium retention (magnesium-sparing effect), similar to potassium.
• C. They cause significant hypomagnesemia.
• D. They have no effect on magnesium levels.

Answer: B. They can promote magnesium retention (magnesium-sparing effect), similar to potassium.

32. For a patient starting spironolactone for HFrEF, when should the first follow-up for potassium and renal function typically occur?

• A. After 6 months
• B. Within 2-3 days, then at 7 days, then monthly for 3 months, then periodically
• C. Only if symptoms of hyperkalemia develop
• D. Annually

Answer: B. Within 2-3 days, then at 7 days, then monthly for 3 months, then periodically (Specific timing varies by guideline, but early and frequent monitoring is key).

33. The EMPHASIS-HF trial primarily investigated the benefits of which aldosterone antagonist in patients with mild HFrEF (NYHA class II)?

• A. Spironolactone
• B. Eplerenone
• C. Finerenone
• D. Canrenone

Answer: B. Eplerenone

34. What is the role of aldosterone in sodium and water homeostasis beyond the kidneys?

• A. It has no effects outside the kidneys.
• B. It can also influence sodium and water transport in other epithelial tissues like the colon and salivary glands.
• C. It primarily causes sodium excretion in the colon.
• D. It blocks vasopressin release.

Answer: B. It can also influence sodium and water transport in other epithelial tissues like the colon and salivary glands.

35. Which of the following is NOT a direct effect of mineralocorticoid receptor blockade by aldosterone antagonists?

• A. Increased sodium excretion
• B. Increased potassium retention
• C. Inhibition of angiotensin II formation
• D. Reduction of aldosterone-induced cardiac and vascular fibrosis

Answer: C. Inhibition of angiotensin II formation (They block aldosterone’s effects, not Ang II formation).

36. The use of finerenone in patients with type 2 diabetes and chronic kidney disease has been shown to reduce the risk of:

• A. Only hypoglycemia
• B. Progression of CKD and cardiovascular events, with potentially less hyperkalemia than traditional MRAs at equipotent doses for these effects.
• C. Developing type 1 diabetes
• D. Weight gain

Answer: B. Progression of CKD and cardiovascular events, with potentially less hyperkalemia than traditional MRAs at equipotent doses for these effects.

37. Which of the following best describes the rationale for using aldosterone antagonists in ascites due to cirrhosis?

• A. To directly increase portal venous pressure.
• B. To counteract the effects of secondary hyperaldosteronism, which contributes to sodium and water retention in cirrhosis.
• C. To improve liver function directly.
• D. To act as a primary antiviral agent.

Answer: B. To counteract the effects of secondary hyperaldosteronism, which contributes to sodium and water retention in cirrhosis.

38. A patient on eplerenone is prescribed itraconazole (a strong CYP3A4 inhibitor). What is the likely consequence?

• A. Decreased eplerenone levels, reducing its efficacy.
• B. Increased eplerenone levels, increasing the risk of hyperkalemia and other adverse effects.
• C. No interaction is expected.
• D. Accelerated metabolism of eplerenone.

Answer: B. Increased eplerenone levels, increasing the risk of hyperkalemia and other adverse effects.

39. Why is eplerenone often preferred over spironolactone if endocrine side effects are a concern?

• A. Eplerenone has a longer half-life.
• B. Eplerenone is significantly more potent as an MRA.
• C. Eplerenone has greater selectivity for the mineralocorticoid receptor and less affinity for androgen and progesterone receptors.
• D. Eplerenone does not require renal dose adjustments.

Answer: C. Eplerenone has greater selectivity for the mineralocorticoid receptor and less affinity for androgen and progesterone receptors.

40. The beneficial effects of aldosterone antagonists on cardiac remodeling include:

• A. Increasing left ventricular chamber size.
• B. Promoting myocyte hypertrophy.
• C. Reducing myocardial fibrosis, ventricular hypertrophy, and improving endothelial function.
• D. Causing direct coronary vasodilation.

Answer: C. Reducing myocardial fibrosis, ventricular hypertrophy, and improving endothelial function.

41. A patient with HFrEF and an eGFR of 25 mL/min/1.73m² and serum K+ of 5.3 mEq/L is being considered for MRA therapy. What is the most appropriate action?

• A. Initiate spironolactone at a high dose.
• B. MRA therapy is likely contraindicated or requires extreme caution and very close monitoring due to severe renal impairment and borderline/high potassium.
• C. Initiate eplerenone without concern.
• D. Initiate finerenone at the standard dose.

Answer: B. MRA therapy is likely contraindicated or requires extreme caution and very close monitoring due to severe renal impairment and borderline/high potassium.

42. “Aldosterone escape” can occur during long-term ACE inhibitor therapy. Aldosterone antagonists are beneficial in this setting because they:

• A. Increase the production of ACE.
• B. Directly block the effects of aldosterone that may still be produced despite ACE inhibition.
• C. Inhibit the metabolism of ACE inhibitors.
• D. Convert angiotensin I to angiotensin II.

Answer: B. Directly block the effects of aldosterone that may still be produced despite ACE inhibition.

43. Which of the following is a crucial counseling point for patients starting an aldosterone antagonist?

• A. To increase their intake of potassium-rich foods and salt substitutes.
• B. To be aware of the signs of hyperkalemia (e.g., muscle weakness, palpitations) and the importance of regular blood tests for potassium and kidney function.
• C. That these drugs primarily work by increasing heart rate.
• D. To discontinue their ACE inhibitor or ARB.

Answer: B. To be aware of the signs of hyperkalemia (e.g., muscle weakness, palpitations) and the importance of regular blood tests for potassium and kidney function.

44. The mineralocorticoid receptor is a nuclear hormone receptor. Aldosterone binding to MR leads to:

• A. Rapid opening of ion channels on the cell surface.
• B. Translocation of the receptor-ligand complex to the nucleus and modulation of gene transcription.
• C. Activation of adenylyl cyclase and increased cAMP.
• D. Inhibition of protein synthesis in the cytoplasm.

Answer: B. Translocation of the receptor-ligand complex to the nucleus and modulation of gene transcription.

45. Compared to spironolactone and eplerenone, finerenone’s non-steroidal structure gives it different physicochemical properties which may influence its:

• A. Complete lack of affinity for the mineralocorticoid receptor.
• B. Tissue distribution, receptor binding kinetics, and cofactor recruitment, potentially leading to more balanced effects on sodium/water vs. potassium.
• C. Inability to be administered orally.
• D. Exclusive metabolism by CYP2C9.

Answer: B. Tissue distribution, receptor binding kinetics, and cofactor recruitment, potentially leading to more balanced effects on sodium/water vs. potassium.

46. The primary site of action for the diuretic effect of aldosterone antagonists is the:

• A. Proximal convoluted tubule
• B. Loop of Henle
• C. Distal convoluted tubule and collecting ducts of the nephron
• D. Glomerulus

Answer: C. Distal convoluted tubule and collecting ducts of the nephron

47. What is the main reason spironolactone causes anti-androgenic effects like gynecomastia?

• A. It directly stimulates estrogen receptors.
• B. It binds to androgen receptors, blocking the effects of androgens, and can also inhibit androgen synthesis.
• C. It increases the conversion of testosterone to estrogen.
• D. It inhibits the metabolism of estrogen.

Answer: B. It binds to androgen receptors, blocking the effects of androgens, and can also inhibit androgen synthesis.

48. A patient taking an aldosterone antagonist should be advised to avoid or use with caution which type of common over-the-counter medication?

• A. Acetaminophen
• B. Antihistamines
• C. NSAIDs (e.g., ibuprofen, naproxen) due to risk of renal impairment and hyperkalemia
• D. Vitamin C supplements

Answer: C. NSAIDs (e.g., ibuprofen, naproxen) due to risk of renal impairment and hyperkalemia

49. The term “potassium-sparing diuretic” accurately describes aldosterone antagonists because they:

• A. Increase potassium excretion.
• B. Decrease potassium excretion by inhibiting aldosterone-mediated potassium secretion in the distal nephron.
• C. Have no effect on potassium levels.
• D. Directly block potassium channels.

Answer: B. Decrease potassium excretion by inhibiting aldosterone-mediated potassium secretion in the distal nephron.

50. The overall goal of adding an aldosterone antagonist to the treatment regimen of a selected HFrEF patient already on an ACEi/ARB/ARNI and beta-blocker is to:

• A. Primarily achieve greater blood pressure reduction.
• B. Further reduce the risk of mortality and heart failure hospitalizations by targeting the deleterious effects of aldosterone.
• C. Replace the need for loop diuretics.
• D. Improve exercise capacity as the sole effect.

Answer: B. Further reduce the risk of mortality and heart failure hospitalizations by targeting the deleterious effects of aldosterone.