Mechanism of Action

Thiazide diuretics act in the distal convoluted tubule, where they block Na+-Cl" cotransport (Fig. 21.4). The Na+-Cl" cotransport takes place on the luminal surface of distal convoluted tubules. Thus, to exert their diuretic action, the thiazides must reach the luminal fluid. Since the thiazide diuretics are largely bound to plasma proteins and therefore are not readily filtered across the glomeruli, access to the luminal fluid is accomplished by the proximal tubule organic acid secretory system. The drugs then travel along the nephron, presumably being concentrated as fluid is abstracted, until they reach their site of inhibitory action in the distal convoluted tubule.

Especially at higher doses, administration of some of the thiazides results in some degree of carbonic anhy-drase inhibition. However, at usual doses, only chloroth-iazide shows any appreciable carbonic anhydrase inhibitory activity.

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