Which of the following diuretics acts by inhibiting Na⁺-K⁺-2Cl⁻ cotransporter in the thick ascending limb of the loop of Henle?

Explanation

## Mechanism of Loop Diuretics **Key Point:** Loop diuretics (furosemide, bumetanide, torsemide, ethacrynic acid) inhibit the Na⁺-K⁺-2Cl⁻ (NKCC2) cotransporter located on the apical membrane of thick ascending limb cells. ## Site of Action Comparison | Diuretic Class | Site of Action | Target Transporter | Potency | | --- | --- | --- | --- | | Loop diuretics | Thick ascending limb | Na⁺-K⁺-2Cl⁻ cotransporter | Most potent | | Thiazides | Distal convoluted tubule | Na⁺-Cl⁻ cotransporter | Moderate | | K⁺-sparing | Collecting duct | ENaC channel / aldosterone | Weak | | Carbonic anhydrase inhibitors | Proximal tubule | Carbonic anhydrase | Weak | **High-Yield:** Furosemide is the most commonly used loop diuretic in clinical practice due to rapid onset (IV: 1 min, oral: 1 hour) and short duration (4–6 hours). **Clinical Pearl:** Loop diuretics are the only diuretics effective in renal failure (GFR < 30 mL/min) because they reach the tubular lumen via active secretion, independent of glomerular filtration. ## Why Loop Diuretics Are Most Potent 1. The thick ascending limb reabsorbs 20–30% of filtered Na⁺ and Cl⁻ 2. This segment is impermeable to water (diluting segment) 3. Blocking NKCC2 prevents the countercurrent multiplier mechanism 4. Results in profound natriuresis and diuresis **Mnemonic:** **FBET** = Furosemide, Bumetanide, Ethacrynic acid, Torsemide (the four loop diuretics).