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:

• Heart Failure with Reduced EF
• Resistant Hypertension
• Cirrhosis with ascites
• Primary hyperaldosteronism

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.

Site of action:

• Collecting duct

Electrolyte effects:

• ↑ Potassium
• ↓ Sodium reabsorption
• Mild diuresis

Diuretic strength:

• Weak compared to Loop Diuretics

HFrEF:

• Proven mortality reduction
• Added to:
  • ACE Inhibitor or ARB
  • ARNI
  • Beta-Blockers
  • SGLT2 Inhibitors

Resistant Hypertension:

• Preferred fourth-line agent

Primary Hyperaldosteronism:

• Diagnostic and therapeutic role

Cirrhosis:

• First-line for ascites management

RALES Trial:

• Reduced mortality in HFrEF
• Reduced hospitalizations

Effect attributed to:

• Neurohormonal modulation
• Anti-fibrotic 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:

• Eplerenone

Avoid in:

• Severe renal impairment
• Baseline hyperkalemia
• Addison disease

Use caution when combined with:

• ACE Inhibitors
• ARBs
• Direct Renin Inhibitors

Monitor:

• Potassium
• Creatinine

Eplerenone:

• More selective aldosterone blocker
• Fewer endocrine side effects
• More expensive

Spironolactone:

• Stronger receptor blockade
• More endocrine effects
• More commonly used

• MRA
• Reduces mortality in HFrEF
• Preferred fourth-line for resistant hypertension
• Causes hyperkalemia
• Causes gynecomastia
• Mortality benefit ≠ diuresis effect

• Heart Failure
• Hypertension
• Diuretics
• Eplerenone
• ACE Inhibitors