Overview Snapshot A 63-year-old man with a history of congestive heart failure presents with increased pedal edema and worsening orthopnea. He reports that he has been taking his lisinopril as prescribed and adhering to a low-salt diet. Physical exam shows 2+ pitting edema in the knees bilaterally and faint crackles on auscultation of the lungs. Left ventricular ejection fraction (LVEF) is measured by echocardiogram and found to be 33%. This is decreased from his last measurement of 38%. He is put on an additional medication. (Congestive heart failure exacerbations) Spironolactone and Eplerenone Mechanism competitive aldosterone receptor antagonist in the cortical collecting tubule reduces potassium secretion by decreasing activity of the epithelial sodium channel (ENAC) and the apical potassium channel Clinical use hyperaldosteronism potassium wasting from loop or thiazide diuretics congestive heart failure (CHF) decreases ventricular remodeling reduces mortality antiandrogenic treatment for female hirsutism Toxicity hyperkalemia can result in arrhythmias spironolactone has antiandrogen effects causes gynecomastia eplerenone causes gynecomastia to a lesser extent Triamterene and Amiloride Mechanism blocks ENAC in the cortical collecting duct, thereby leading to decreased sodium reabsorption indirectly reduces potassium secretion by creating a more positive luminal potential indirectly decreases activity of the apical proton ATPase and reduces secretion of protons does not cause anti-androgen effects Clinical use congestive heart failure (CHF) potassium wasting lithium-induced nephrogenic diabetes insipidus amiloride Toxicity hyperkalemia normal anion gap metabolic acidosis