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Loop diuretics

Loop Diuretics: Mechanism & side effects Inhibit Na+/K+/2Cl- (NKCC) symporter at thick ascending limb of Loop of Henle (aLOH) Authors: Andrew Wu, Rafael Sanguinetti Reviewers: Luiza Radu, Adam Bass* * MD at time of publication Over-inhibition of ion symporter in ear at high concentrations Damage to tight junctions in the blood vessel epithelium in the ear Disruption of the blood- cochlear barrier Hearing loss Opening of ATP-sensitive K+ channels on pancreatic β- cells causes efflux of K+ ↓ Intracellular K+ causes a negative intracellular charge ↓ Ability for pancreatic β- cells to depolarize & release insulin Hyperglycemia (rare) Stimulation of prostaglandin E2 (PGE2) synthesis in the cortical & medullary aLOH Stimulation of endothelial nitric oxide synthase releases nitric oxide Systemic venodilation (dilation of veins) ↓ Systemic vascular resistance ↓ Blood pressure ↓ Na+ in renal interstitium ↓ Water reabsorption (water follows Na+) Interstitial washout (↑ NaCl & water wasting in interstitium) ↓ Sodium (Na+) reabsorption ↑ Positive luminal charge at thick aLOH ↓ Electrochemical gradient reduces cellular transport of cations ↓ Ca2+ & Mg2+ reabsorption in the aLOH Hypocalcaemia & hypomagnesemia ↑ Na+ delivery to the distal convoluted tubule (DCT) ↑ Intracellular Na+ at collecting duct ↑ K+ efflux via renal outer medullary potassium channel (ROMK) ↓ Fluid status ↓ Serum Na+ ↓Serum Cl- ↑ Luminal K+ at alpha intercalated cell Chemical gradient ↑ K+/H+ antiporter activity ↑ K+ excretion Hypokalemia Chemical gradient shifts K+ into cells creating a charge gradient to shift H+ out Hyponatremia Hypovolemia Hypochloremia ↓ Volume status activates angiotensin II, which plays a role in sodium and volume retention ↑ Na+/H+ antiporter 3 (NHE3) activity in the proximal tubule Kidneys excrete & conserve ions to preserve intracellular charge gradient ↑ H+ loss in the urine ↓ Serum H+ ↑ Proximal Na+ reabsorption causes ↑ urate reabsorption via urate-hydroxyl exchangers Hyperuricemia Contraction alkalosis (loss of Na+-rich, HCO3- low fluid) & hypokalemia ↑ Serum HCO3- Metabolic alkalosis (systemic pH > 7.45 due to metabolic process) Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 18, 2024 on www.thecalgaryguide.com