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Potassium-Sparing-Diuretics-Mechanism-of-Action-and-Side-Effects

Potassium-Sparing Diuretics: Mechanism of Action and Side Effects Potassium-Sparing Diuretics Authors: Samin Dolatabadi, Yan Yu* Reviewers: Jessica Krahn, Timothy Fu, Juliya Hemmett* * MD at time of publication Epithelium Sodium Channel Blockers (Amiloride and Triamterene) Inhibit Na+ channels (involved in Na+ reabsorption) in the luminal membrane of the principal cells in the cortical collecting duct Aldosterone Antagonists (Spironolactone and Eplerenone) Competitively blocks mineralocorticoid receptors and ↓ aldosterone effect in the renal tubules and throughout the body ↓ aldosterone effectà↓ expression of basolateral Na+/K+ pumps & luminal epithelium Na+ channels on the principal cells of cortical collecting duct Spironolactone’s molecular structure is similar to that of steroid hormonesàspironolactone can also block androgen receptors Anti-androgenic effects (due to ↓ androgen function in reproductive organs, skin, and on brain centers) Triamterene can form triamterene crystals and granular casts (unclear mechanism) ↓ Na+ reabsorption by principal cells ↓ in serum Na+ concentration: Hyponatremia ↓ K+ pumped out into the tubule by principal cells Crystals & casts obstruct tubular lumen → inflammation (unclear mechanism) Triamterene crystals are directly cytotoxic to tubular cells Only ~2-5% of Na+ filtered by the glomerulus is normally reabsorbed in the cortical collecting ductàthe ↑ in Na+ retained in cortical collecting duct is mild Water follows Na+ to maintain a balanced osmotic pressureà↑ in water in cortical collecting duct available for excretion ↑ positive charges in lumen relative to surroundings generates an electropositive tubular lumen Unfavorable electrical gradient ↓ secretion of positive charged ions into electropositive lumen ↓ libido Menstrual abnormalities (in women) ↓ acne Gynecomastia (in men) ↓ secretion of K+ ↑ in serum K+ concentration: Hyperkalemia Cardiac Arrythmias (See relevant slide on Hyperkalemia: Clinical Findings) Interstitial inflammation and tubular injury Drug-induced Nephrotoxicity Mild Diuresis ↓ blood volume ↓ Blood pressure/ Hypotension ↓ secretion of H+ ↑ in serum H+ concentration: Metabolic Acidosis Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published February 15, 2021 on www.thecalgaryguide.com