The kidney is a complex organ maintaining fluid, electrolyte, and acid–base balance. It also serves an endocrine function by secreting renin and erythropoietin. Diuretics are drugs that act on the kidney to increase urine production and can be divided into the following groups:

• Thiazides

• Loop diuretics

• Potassium sparing

• Aldosterone antagonists

• Osmotic

• Carbonic anhydrase inhibitors

Thiazides (bendroflumethazide, chlorothiazide, metolazone)

Thiazides (which are chemically related to the sulphonamides) are widely used in the treatment of mild heart failure and hypertension, alone or in combination with other drugs. They have also been used in diabetes insipidus where they may increase the sensitivity of the collecting ducts to remaining ADH or cause Na+ depletion and therefore reduced water absorption in the proximal tubule. In addition, they have been used in renal tubular acidosis. The main difference among the drugs is their rate of absorption from the gut due to differences in lipid solubility and rate of onset and duration of action due to differences in handling by the renal tubule.

Mechanism of action

Thiazides are moderately potent and act mainly on the early segment of the distal tubule by inhibiting Na+ and Cl− reabsorption. This leads to increased Na+ and Cl− excretion and therefore increased water excretion. The increased Na+ load reaching the distal tubule stimulates an exchange with K+ and H+ so that thiazides tend to precipitate a hypokalaemic, hypochloraemic alkalosis. Thiazides also reduce carbonic anhydrase activity resulting in an increased bicarbonate excretion; however, this effect is small and of little clinical significance.