Mechanisms-Loop diuretics

• inhib NaK2Cl cotransporter in thick ascending limb (ThAL, site of 25% Na reabsorp) → ↓ medullary osmotic gradient & ↓ free H2O reabsorption via ADH

• Transient venodilation may aid in pulmonary congestion (NEJM 1973;288:1087)

• Response is fxn of amt of drug excreted; ∴ ↑ dose needed in renal insufficiency, CHF

• Sigmoidal dose response curve; ∴ ↑ dose until induce diuresis, ↑↑ dose beyond that point yields diminishing returns compared with ↑ frequency of dosing