Potassium Sparing Diuretics

4. Potassium Sparing Diuretics

ENaC Inhibitors
ENaC is a Na+ pump on the apical side of principal cells in the collecting duct. Amiloride blocks Na+ reabsorption causing a decrease in Na+/K+ ATPase activity causing K+ retention. As a result of the reduced K+ electrochemical gradient, there is increased reabsorption of H+, Ca2+, and Mg2+. ENaC polymorphism (T594M) can cause increased sensitivity to the drug.

ENaC inhibitors can be used to treat:
-hypertension
-Li+ induced nephrogenic diabetes
-Liddle Syndrome (pseudohyperthyroidism)

Adverse effects of ENaC inhibitors include:
-hyperkalemia (contradicted in those who have it)

Drug interactions with ENaC inhibitors include:
-ACE inhibitors and ARB (hyperkalemia)
-NSAIDs (hyperkalemia)
-K+ supplements (hyperkalemia)

Mineralocorticoid Receptor Inhibitors
Aldosterone binds to mineralocorticoid receptors, increasing Na+/Cl- reabsorption and K+/H+ secretion. MR inhibitors, such as spironolactone and eplerenone, block ALDO from binding. As a result, there is increased Na+ and Cl- excretion, and increased H+ secretion. Spironolactone can cause antiandrogenic effects like gynecomastia and impotence.

MR inhibitors can be used to treat:
-edema
-hypertension
-primary aldosteronism
-heart failure
-hirsutism (interfere with testosterone)
-hepatic cirrhosis (spironolactone is drug of choice)

Drug interactions with MR inhibitors include:
-Digoxin (decreased clearance with spironolactone)
-CYP3A4 mediated interactions (eplerenone)