Pathophysiology
Clinical meaning
Diuretic selection requires understanding where each drug class acts along the nephron and how site-of-action determines efficacy, electrolyte effects, and clinical indications. 1. Loop diuretics (furosemide, bumetanide, torsemide) act on the thick ascending limb of the loop of Henle by inhibiting the Na+/K+/2Cl- cotransporter (NKCC2). This site reabsorbs ~25% of filtered sodium, making loop diuretics the most POTENT diuretics available. They also impair the medullary concentration gradient (countercurrent multiplication), reducing the kidney's ability to concentrate urine. Effect: massive natriuresis and diuresis, calciuria (loop diuretics WASTE calcium — opposite of thiazides), hypokalemia, hypomagnesemia, metabolic alkalosis. Key pharmacokinetics: furosemide has variable oral bioavailability (~50%), short duration (6 hours); torsemide has more predictable absorption (~80%) and longer duration (12-16 hours). 2. Thiazide diuretics (hydrochlorothiazide, chlorthalidone, metolazone) act on the distal convoluted tubule by inhibiting the Na+/Cl- cotransporter (NCC). This site reabsorbs only ~5% of filtered sodium, so thiazides are LESS potent than loops. However, they have superior antihypertensive effect at lower doses due to additional vasodilatory properties. Effect: moderate natriuresis, hypocalciuria (thiazides RETAIN calcium — useful in calcium nephrolithiasis and osteoporosis), hypokalemia, hyperglycemia,...