Aldosterone Antagonists

Aldosterone antagonists are potassium sparing diuretics that work by inactivating the spironolactone receptor complex. These medications prevent the translocation of this complex into the cell and ultimately reduce the activation of sodium/potassium exchange proteins in the renal tubules, which reduces sodium reabsorption.  Aldosterone antagonists are used to treat resistant hypertension, heart failure, ascites and liver cirrhosis, and as a general diuretic as a result of this mechanism of action.  

Additionally, spironolactone -- but not the more receptor-selective eplerenone -- blocks androgen and progesterone receptors at higher doses, which assists in treatment of PCOS, where androgen levels are elevated.  

Class Drugs

• Eplerenone

• Spironolactone

Class Mechanism of Action

Inactivates spironolactone receptor complex

• Receptor complex cannot translocate into the nucleus of cell, which limits production of proteins that stimulate sodium/potassium (Na/K) exchange proteins in the tubules

• Reduces Na reabsorption

• Retains K and H ions (potassium-sparing)

Renal Tubule - Primary sites of action of diuretics.

Class Applications

Resistant Hypertension

Diuretic

• Given in conjunction with thiazide diuretic to counter-act potassium wasting

Ascites/Liver Cirrhosis

• Counteracts secondary hyperaldosteronism, which causes edema in patients with liver cirrhosis

Heart Failure

• Prevents remodeling of cardiac tissue

• Decreases mortality in heart failure

Polycystic Ovary Syndrome (PCOS)

• At high doses, spironolactone (not eplerenone) also blocks androgen receptors

• Results in decreased androgen effects, which are elevated in PCOS

Secondary Hyperaldosteronism

• Blocks effects of overproduction of aldosterone seen in liver cirrhosis and nephrotic syndrome

Class Adverse Effects

• Hyperkalemia (both drugs)

• Gynecomastia, menstrual irregularities (spironolactone -- due to non-selective binding to androgen and progesterone receptors; eplerenone is far more selective for the mineralocorticoid receptor and causes these effects much less often)

Drug Table

Drug Name	Application	Comments	Image
Eplerenone			"Omar Epps" "Lee Jeans" "One"
Spironolactone			"Spiral" "Lactose Free Milk"