What is the mechanism of loop diuretics and their clinical use in heart failure?

• A. Inhibit Na-Cl cotransporter in the distal tubule.
• B. Inhibit Na-K-2Cl cotransporter in the thick ascending limb.
• C. Block Na channels in the collecting duct.
• D. Inhibit carbonic anhydrase in the proximal tubule.

Answer: (B)

Loop diuretics work by blocking the Na-K-2Cl cotransporter (NKCC2) in the thick ascending limb of the loop of Henle. This transporter normally reabsorbs sodium, potassium, and chloride from the tubular fluid; inhibiting it stops this reabsorption, so large amounts of NaCl and water stay in the urine. The resulting potent diuresis lowers extracellular fluid, which reduces preload and venous congestion. That relief from volume overload is why loop diuretics are especially useful in heart failure—to rapidly decongest edema and pulmonary congestion. They act high in the nephron, so they’re effective even when GFR is reduced, making them the go-to choice for swift symptom control. Common drawbacks include potassium loss, potential uric acid retention, and risk of ototoxicity at high doses.