The main action of thiazides (hydrochlorothiazide) and related diuretics (chlorthalidone, indapamide) is to inhibit the reabsorption of sodium and chloride in the proximal (diluting) segment of the distal tubule. These drugs do not have significant natriuretic activity when used in low doses for the treatment of hypertension. They lower blood pressure by a vasodilator effect, which appears to result from activation of calcium-dependent potassium channels in blood vessels and probably in the heart. In renal impairment they are less effective as diuretics but may still lower blood pressure. Duration of action and equivalent dose varies widely, but as single agents they are equivalent in most aspects. Although they are effective diuretics in mild heart failure, their main clinical application is in hypertension.

Adverse effects include hypokalaemia, hyponatraemia, and elevated plasma glucose, urate and calcium. However, with the low doses currently recommended, metabolic adverse effects are minimised. Higher doses are associated with increased risk of metabolic disturbances without additional antihypertensive effect. Hypersensitivity and photosensitivity may occur. Thiazide diuretics are chemically related to sulfonamides, and should not be used in patients who have had a serious allergic reaction to sulfonamides. Although indapamide has a sulfur molecule in its structure it is not a sulfonamide. It has, however, also been associated with skin rashes.