Diuretics

The main function of the kidney is maintenance of the milieu internal. Diuretics work by altering renal function and affecting this balance. However, diuretics are crucial for the management of cardiovascular disease. They increase the excretion of Na+ ions and water and they decrease the reabsorption of Na+ and (usually) Cl- ions from the filtrate, increased water loss being secondary to the increased excretion of NaCl (natriuresis). Because a very large proportion of NaCl and water that passes into the tubule in the glomerulus is reabsorbed, a small decrease in reabsorption can cause a marked increase in Na+ ion excretion. Drugs that cause NaCl loss by a direct action on cells must obviously affect those parts of the nephron where solute reabsorption occurs. Most Na+ ion reabsorption occurs in the PCT, however, carbonic anhydrase inhibitors, the only class of diuretic drugs that acts on the proximal tubule, are not particularly potent. This is because they inhibit NaHCO3- reabsorption rather than NaCl reabsorption, as there is less HCO3- in the glomerular filtrate there is a reduced effect on Na+ ion reabsorption. Plasma HCO3- concentration declines during chronic use of these drugs because of the increased urinary excretion of HCO3- further limiting the diuretic potency of carbonic anhydrase inhibitors. Carbonic anhydrase inhibitors-for example acetazolamide increase excretion of bicarbonate with accompanying Na+, K+ ions and water, resulting in an increased flow of an alkaline urine and metabolic acidosis. These agents, although not now used as diuretics, are still used in the treatment of glaucoma to reduce the formation of aqueous humour, and also in some unusual types of infantile epilepsy. Urinary loss of bicarbonate depletes extra-cellular bicarbonate, and the diuretic effect of carbonic anhydrase inhibitors is consequently self-limiting. Instead, the main therapeutically useful diuretics act on the: ? Thick ascending loop of Henle ? Early distal tubule ? Collecting tubules and ducts Loop diuretics are the most powerful diuretics, capable of causing the excretion of 15-25% of filtered Na+ ions. Their action is often described in a phrase that conjures up a rather uncomfortable picture-as causing torrential urine flow . The main example is furosemide; bumetanide is an alternative agent. These drugs act on the thick ascending limb, inhibiting the NaKCC carrier in the luminal membrane by combining with its Cl- binding site.