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Metolazone + furosemide is a combination diuretic therapy that produces a synergistic effect by targeting different sites in the renal tubule. Furosemide is a loop diuretic that inhibits the sodium-potassium-chloride cotransporter in the thick ascending limb of the loop of Henle, while metolazone is a thiazide-like diuretic that acts on the distal convoluted tubule to inhibit sodium and chloride reabsorption. When used together, they create a powerful diuretic effect that is particularly useful in patients with severe fluid retention who have become resistant to loop diuretics alone. This combination is primarily used in the management of severe congestive heart failure, cirrhosis with ascites, and refractory edema[1][3].
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