What is the mechanism of action of thiazide diuretics?

Thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone) block the sodium-chloride (Na+/Cl-) cotransporter in the proximal segment of the distal convoluted tubule (DCT), inhibiting 3-5% of sodium reabsorption. This leads to natriuresis, diuresis, and reduced intravascular volume, which lowers blood pressure. Unlike loop diuretics, which act on the thick ascending limb of the loop of Henle, thiazides uniquely increase calcium reabsorption (useful in nephrolithiasis). Common side effects include hypokalemia, hyponatremia, hyperuricemia, and hyperglycemia.