Thiazides block Na+ and Cl- reabsorption in the distal tubule. There is usually passive Na+ and Cl- co transport. With this blocked, natriuresis occur. The distal convoluted tubule accounts for 5% of total sodium chloride reabsorption. Thiazides elevate LDL cholesterol, reduce urinary calcium excretion and can cause impotence. Hypercalciuria can be treated with thiazides.

Thiazides can cause thrombocytopaenia, hypokalaemia (blocking NaCl channels), and hyperuricaemia.