====== Spironolactone ======

Spironolactone is a [[cardio:diuretics:mra|Potassium-Sparing Diuretic]] and a Mineralocorticoid Receptor Antagonist (MRA).

It blocks the effects of aldosterone at the collecting duct.

Used in:

  * [[cardio:heart_failure:start|Heart Failure with Reduced EF]]
  * Resistant [[cardio:hypertension:start|Hypertension]]
  * Cirrhosis with ascites
  * Primary hyperaldosteronism

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===== 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.

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===== Renal Effects =====

Site of action:
  * Collecting duct

Electrolyte effects:

  * ↑ Potassium
  * ↓ Sodium reabsorption
  * Mild diuresis

Diuretic strength:
  * Weak compared to [[cardio:diuretics:loop:start|Loop Diuretics]]

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===== Clinical Use =====

HFrEF:

  * Proven mortality reduction
  * Added to:
      * [[cardio:raas:acei|ACE Inhibitor]] or [[cardio:raas:arb|ARB]]
      * [[cardio:raas:arni|ARNI]]
      * [[cardio:beta_blockers:start|Beta-Blockers]]
      * [[cardio:hf:sglt2:start|SGLT2 Inhibitors]]

Resistant Hypertension:

  * Preferred fourth-line agent

Primary Hyperaldosteronism:

  * Diagnostic and therapeutic role

Cirrhosis:

  * First-line for ascites management

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===== Mortality Data =====

RALES Trial:

  * Reduced mortality in HFrEF
  * Reduced hospitalizations

Effect attributed to:

  * Neurohormonal modulation
  * Anti-fibrotic effects

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===== 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:
  * [[cardio:hf:eplerenone|Eplerenone]]

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===== Contraindications =====

Avoid in:

  * Severe renal impairment
  * Baseline hyperkalemia
  * Addison disease

Use caution when combined with:

  * [[cardio:raas:acei|ACE Inhibitors]]
  * [[cardio:raas:arb|ARBs]]
  * [[cardio:raas:direct_renin_inhibitor|Direct Renin Inhibitors]]

Monitor:

  * Potassium
  * Creatinine

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===== Spironolactone vs Eplerenone =====

[[cardio:hf:eplerenone|Eplerenone]]:

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

Spironolactone:

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

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===== Clinical Pearls =====

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

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===== Related =====

  * [[cardio:heart_failure:start|Heart Failure]]
  * [[cardio:hypertension:start|Hypertension]]
  * [[cardio:diuretics:start|Diuretics]]
  * [[cardio:hf:eplerenone|Eplerenone]]
  * [[cardio:raas:acei|ACE Inhibitors]]