thiazide diuretic

Mechanism: Thiazides block the Na+/Cl- cotransporter (NCC) in the early distal convoluted tubule, decreasing NaCl reabsorption. This leads to increased sodium delivery to the collecting duct, promoting K+ and H+ secretion. Unlike loop diuretics, thiazides cause increased calcium reabsorption (paradoxically), making them useful in prevention of calcium-containing kidney stones. Clinical uses: essential hypertension (first-line per JNC8), mild heart failure, nephrogenic diabetes insipidus (paradoxical antidiuretic effect via volume depletion causing compensatory proximal reabsorption), and idiopathic hypercalciuria/calcium nephrolithiasis. Adverse effects: hypokalemia, hyponatremia, hypercalcemia, hyperglycemia, hyperlipidemia, hyperuricemia (can precipitate gout), and sulfa allergy (cross-reactivity with sulfonamides). Mnemonic: 'hyperGLUC' - hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia. Contraindicated relatively in sulfa-allergic patients and used cautiously in renal impairment (loop diuretics preferred in advanced CKD). Pharmacokinetics: effective only when GFR is adequate (thiazides lose efficacy in severe renal failure, GFR <30 mL/min, except metolazone which retains some efficacy). Chlorthalidone has longer half-life and is often preferred for BP control based on outcome trials (ALLHAT). Key exam associations: thiazide-induced hyponatremia (SIADH-like), thiazide use in nephrogenic DI, thiazide use to distinguish causes of hypercalciuria vs hypercalcemia workup.