K-Sparing Diuretics

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