About Hydrochlorothiazide Thiazide derivatibve, Diuretic. Mechanism of Action of Hydrochlorothiazide It is thiazide diuretic which exerts its action by acting at site-3(central dilating segment of early distal tubule). It binds to Na+Cl- symporter and inhibits Na+Cl- symport at the luminal membrane. It has additional carbonic anhydrase inhibitory actions in proximal tubules. It increases natriuresis, kaliuresis and diuresis. It decreases Ca2+ excretion and increases Mg2+excretion. It also has minor carbonic anhydrase inhibitory action. It also causes direct arteriolar vasodilatation and decreases total peripheral resistance. The antihypertensive actions of the drug may be attributable to depletion of sodium and subsequent reduction in plasma volume and a decrease in peripheral resistance. Decrease in peripheral resistance is due to either the loss of sodium from the arteriolar wall or a direct action on the vascular bed.