What is a Diuretic?

Diuretics are drugs that can increase the amount of water and sodium that is excreted in the urine. There are several classes of diuretics, each with a different mechanism of action. The main classes of diuretics and their mechanisms are described below.

Loop diuretics
These are the most effective type of diuretic, leading to the excretion of up to 20% of the filtered salt (sodium chloride) and water. Usually, only around 0.4% of the filtered sodium passes into the urine during renal reabsorption. The agents prevent the body from reabsorbing sodium at the ascending loop of Henle in the nephron. This sodium is then excreted, along with the water that follows it. Examples of drugs in this class include furosemide, ethacrynic acid, torsemide and bumetanide.

Thiazide diuretics
Drugs of this class inhibit the sodium-chloride symporter, preventing the retention of water as well as sodium. Thiazides are used as antihypertensive drugs due to their ability to decrease preload and therefore blood pressure. One example of a thiazide diuretic is hydrochlorothiazide.

Carbonic Anhydrase Inhibitors
These drugs inhibit the enzyme carbonic anhydrase which has the effect of decreasing the reabsorption of bicarbonate in the proximal tubule. This leads to retention of bicarbonates and potassium in the urine and decreased sodium absorption.

Potassium-sparing diuretics
Both thiazides and loop diuretics cause the body to lose potassium, depleting the body’s stores of this important electrolyte. The potassium-sparing diuretics promote diuresis without causing the loss of potassium. Drugs in this class include:

• Aldosterone antagonists – Aldosterone normally adds sodium channels to principle cells in the collecting duct of the nephron but drugs such as spironolactone block aldosterone’s entry into the principle cells, therefore preventing the reabsorption of sodium and water.
• Epithelial sodium channel blockers – These directly prevent sodium from entering the epithelial sodium (ENaC) channels, which are found in the apical membrane of the collecting tubule. Two examples include amiloride and triamterene.

Osmotic diuretics
Osmotic diuretics inhibit the reabsorption of sodium and water, increasing the osmolarity of the blood and the renal filtrate. Examples of these agents include isosorbide and mannitol, which may be used for the following clinical purposes:

• Reduction of intracranial pressure or pressure within the skull
• Treatment of oliguric renal failure
• Transportation of drugs straight to the brain