Spironolactone
Spironolactone is a Potassium-Sparing Diuretic and a Mineralocorticoid Receptor Antagonist (MRA).
It blocks the effects of aldosterone at the collecting duct.
Used in:
- Resistant Hypertension
- Cirrhosis with ascites
- Primary hyperaldosteronism
Mechanism of Action
Spironolactone competitively antagonizes the mineralocorticoid (aldosterone) receptor.
Aldosterone normally:
- ↑ ENaC expression
- ↑ Na⁺ reabsorption
- ↑ K⁺ secretion
- Promotes myocardial fibrosis
Blocking aldosterone results in:
- ↓ Sodium reabsorption
- ↓ Water retention
- ↑ Potassium retention
- ↓ Cardiac remodeling and fibrosis
The mortality benefit in HFrEF is primarily due to neurohormonal blockade — not diuresis.
Renal Effects
Site of action:
- Collecting duct
Electrolyte effects:
- ↑ Potassium
- ↓ Sodium reabsorption
- Mild diuresis
Diuretic strength:
- Weak compared to Loop Diuretics
Clinical Use
HFrEF:
- Proven mortality reduction
- Added to:
- ACE Inhibitor or ARB
Resistant Hypertension:
- Preferred fourth-line agent
Primary Hyperaldosteronism:
- Diagnostic and therapeutic role
Cirrhosis:
- First-line for ascites management
Mortality Data
RALES Trial:
- Reduced mortality in HFrEF
- Reduced hospitalizations
Effect attributed to:
- Neurohormonal modulation
- Anti-fibrotic effects
Adverse Effects
Electrolytes:
- Hyperkalemia
- Mild hyponatremia
Endocrine Effects (due to non-selectivity):
- Gynecomastia
- Impotence
- Menstrual irregularities
These occur because spironolactone also blocks:
- Androgen receptors
- Progesterone receptors
Less endocrine side effects with:
Contraindications
Avoid in:
- Severe renal impairment
- Baseline hyperkalemia
- Addison disease
Use caution when combined with:
Monitor:
- Potassium
- Creatinine
Spironolactone vs Eplerenone
- More selective aldosterone blocker
- Fewer endocrine side effects
- More expensive
Spironolactone:
- Stronger receptor blockade
- More endocrine effects
- More commonly used
Clinical Pearls
- MRA
- Reduces mortality in HFrEF
- Preferred fourth-line for resistant hypertension
- Causes hyperkalemia
- Causes gynecomastia
- Mortality benefit ≠ diuresis effect