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