diuretics

diuretics Diuresis is increased urine flow, and diuretics are substances which elicit diuresis. Strictly speaking, by this definition, water is a diuretic, because ingestion of excess water increases urine flow. In medicine and pharmacology, however, the term ‘diuretic’ has come to have a more specific meaning. Diuretics are therapeutic agents which act on the kidneys. They are used to reduce the extracellular fluid volume (see body fluids), and they also reduce the effective circulating blood volume. They are widely used in patients with hypertension and with congestive heart failure. In the latter group, diuretics are used to reduce oedema (tissue swelling due to excess fluid). They have also been used as an aid to slimming, though this is not medically approved.

In the first 20 years of the twentieth century, the diuretics used were theophylline (found in dandelions) and caffeine (in tea and coffee). In 1919, mercurial drugs came into use, followed in the 1950s by thiazides. Details follow of diuretics still widely used.

In the kidneys, water and dissolved substances are filtered from the circulating blood into the microscopic nephrons; most of this water is normally reabsorbed into the blood, whilst the solutes are variously dealt with — retained or rejected according to need.

Water reabsorption from the fluid in the tubules of the nephrons is dependent primarily on reabsorption of sodium ions — the more sodium ions are retrieved, the more water accompanies them back into the blood. The term ‘diuretic’ therefore generally refers to agents which inhibit tubular sodium reabsorption, which occurs to the greatest extent in the first (proximal) part of the tubules through which the fluid flows. With the exception of osmotic diuretics (see below), most diuretics are organic acids, and as such are secreted from the blood into the fluid in the proximal tubules, whence they exert their effects. There are a number of different chemical types of diuretic, and several sites of action within the nephron.

Osmotic diuretics

A straightforward cause of diuresis is the filtration of large amounts of any substance which cannot be reabsorbed by the nephrons. In diabetes mellitus, for example, the plasma glucose concentration (blood sugar) is increased, and the amount of glucose filtered overwhelms the nephrons' reabsorptive mechanism, so that glucose is excreted in the urine, and there is an increased volume of urine. The glucose is acting as an osmotic diuretic. Likewise, a completely non-reabsorbable sugar, mannitol, is often used as an osmotic diuretic agent. So, how do osmotic diuretics work?

When the proximal tubule reabsorbs sodium ions, water normally follows by osmosis, causing the concentration of non-reabsorbable solutes in the tubular fluid to increase. This limits water reabsorption. If there is additional solute in the fluid (as in the glucose example above) less water than normal follows the sodium ions. This discrepancy results in a lowering of sodium ion concentration in the tubular fluid, and in turn a diminished rate of sodium ion reabsorption. Hence there is increased excretion of both sodium ions and water.

Loop diuretics

Most of the diuretics introduced in recent years are ‘loop’ diuretics — their primary sites of action in the kidneys are the loops of Henle, which the fluid reaches after leaving the proximal tubule. Here sodium ions are normally ‘pumped’ out of this fluid and into the fluid which surrounds the loops and the next channels, the collecting ducts, helping to establish an osmotic gradient which will draw more water out of the incoming fluid. Ethacrynic acid, bumetanide, piretanide, and frusemide are loop diuretics. They act by blocking this movement of sodium, so both sodium and water reabsorption are impaired, and more remains to reach the urine. Loop diuretics also increase potassium loss in the urine, so they are often combined with a dietary potassium supplement.

Other diuretics

Spironolactone competes with the hormone aldosterone for receptor sites in the cells of the distal tubules of the nephrons, which the fluid reaches from the loops of Henle. Since aldosterone promotes absorption of sodium from the tubular fluid, and secretion of potassium into it, spironolactone opposes these actions, enhancing excretion of sodium in the urine — and of water along with it — and decreasing potassium excretion. The diuretics triamterene and amiloride have similar overall effects, though by different molecular mechanisms.

Chris Lote

See also kidneys; urine; water balance.