Learning Objective

Understand the mechanism, clinical uses, and side effects of potassium-sparing diuretics and how they interact with other diuretics.

Spironolactone

Mechanism

Aldosterone receptor antagonist

Clinical Uses

Hyperaldosteronism, CHF (improves survival), adjunct to K⁺ wasting diuretics, female hirsutism (antiandrogen effect)

Key Side Effects

Hyperkalemia, metabolic acidosis, antiandrogen effects (gynecomastia, menstrual irregularities)

Eplerenone

Mechanism

Selective aldosterone receptor blocker

Clinical Uses

CHF, hyperaldosteronism

Key Side Effects

Hyperkalemia; less antiandrogenic effect than spironolactone

Clinical Notes:

• K⁺-sparing diuretics reduce K⁺ and H⁺ excretion, which can counteract hypokalemia and alkalosis caused by loop or thiazide diuretics.
• Combining with ACE inhibitors or ARBs can lead to dangerous hyperkalemia.
• Spironolactone’s antiandrogenic effects limit its use in men (gynecomastia) but can be beneficial in women with hirsutism.

High-Yield Step 1 Points:

• Collecting duct action: Site of K⁺ and H⁺ regulation; these drugs act “downstream,” so they don’t cause significant diuresis alone.
• Aldosterone blockers vs. Na⁺ channel blockers: Both conserve K⁺, but only aldosterone blockers affect RAAS-mediated processes like cardiac remodeling in CHF.
• Amiloride for lithium-induced NDI: Blocks Li⁺ entry into principal cells, reducing nephrogenic DI.

Activity