Pharmacology for Anaesthesia and Intensive Care

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Diuretics

The kidney is a complex organ maintaining fluid, electrolyte, and acid–base balance.

Italso 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 car-

bonic anhydrase activity resulting in an increased bicarbonate excretion; however,

this effect is small and of little clinical significance.

Metolazone has very powerful synergistic effects when combined with a loop

diuretic and is useful in cases of renal failure.