Is Spironolactone a Diuretic?
Yes, spironolactone is definitively a potassium-sparing diuretic that acts as an aldosterone receptor antagonist in the distal convoluted renal tubule. 1
Mechanism of Diuretic Action
Spironolactone functions as a diuretic through competitive binding at aldosterone-dependent sodium-potassium exchange sites in the distal convoluted renal tubule. 1 This mechanism causes:
- Increased sodium and water excretion while simultaneously retaining potassium, distinguishing it from loop and thiazide diuretics that cause potassium loss. 1
- Natriuresis and diuresis that typically begins 3-5 days after treatment initiation, reflecting the lag time for full pharmacologic effect. 2
- Aldosterone antagonism that is particularly effective in conditions with elevated aldosterone levels, such as heart failure, cirrhosis, and primary hyperaldosteronism. 1
Classification Among Diuretics
Spironolactone belongs to the potassium-sparing diuretic class, which also includes triamterene and amiloride. 3 However, it differs from these agents because:
- It is the most potent mineralocorticoid receptor antagonist currently used in clinical practice. 2
- Unlike triamterene and amiloride, which directly block sodium channels, spironolactone works through aldosterone receptor antagonism. 1
- It can be used alone or combined with loop diuretics (furosemide, bumetanide) or thiazides that act more proximally in the renal tubule to enhance overall diuretic efficacy. 1
FDA-Approved Diuretic Indications
The FDA recognizes spironolactone as a diuretic for:
- Congestive heart failure with edema and fluid retention. 4, 1
- Hepatic cirrhosis with ascites, where it is the first-line diuretic with a 95% response rate compared to 52% for furosemide alone. 2
- Primary hyperaldosteronism and conditions with secondary aldosteronism. 1
- Nephrotic syndrome and other edematous states. 1
Critical Distinction: Potassium-Sparing Properties
A crucial caveat is that spironolactone's potassium-sparing effect creates significant hyperkalemia risk, particularly when combined with:
- ACE inhibitors or angiotensin receptor blockers. 1
- Potassium supplements or other potassium-sparing diuretics. 1
- NSAIDs, heparin, or trimethoprim. 1
- In patients with renal insufficiency, diabetes, or advanced age. 2
Potassium monitoring is mandatory at baseline, 1 week, 4 weeks, then at 1,2,3, and 6 months, and every 6 months thereafter. 2 If potassium exceeds 5.5 mmol/L, reduce the dose; if it reaches ≥6.0 mmol/L, stop spironolactone immediately. 2
Beyond Diuresis: Additional Pharmacologic Effects
While spironolactone is unequivocally a diuretic, it also possesses anti-androgenic properties that lead to off-label uses in acne treatment (particularly in women) and other androgen-mediated conditions. 3, 4 These anti-androgenic effects cause common side effects including gynecomastia in men (10% in major trials), decreased libido, and menstrual irregularities in women (15-30% of patients). 3, 4