The different classes of diuretics have different mechanisms of action but the overall aim of diuretic therapy is to increase the amount of water excreted in the urine. Some of the mechanisms of the different diuretics are described below:
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 the retention of potassium in the urine and decreased sodium absorption. Decreased sodium absorption leads to a decrease in the reabsorption of water.
These drugs act by inhibiting the Na+/K+/2Cl- transporter protein, present in the walls of the ascending loop of Henle. These agents cause a reduction in the reabsorption of NaCl or salt, which significantly increases diuresis. Patients taking a loop diuretic may also lose too much potassium and a doctor may prescribe a potassium supplement to take alongside the therapy. One example of a loop diuretic is furosemide.
These drugs act by inhibiting NaCl reabsorption in the distal convoluted tubule of the kidney. This action is mediated through suppression of the sodium chloride co-transporter. The main conditions these agents are used to treat include hypertension (high blood pressure), heart failure, kidney stones and nephrogenic diabetes insipidus. One example of a drug in this class is hydrochlorothiazide.
These agents increase diuresis, but without causing potassium to be lost from the body. One widely used example of a potassium-sparing diuretic is spironolactone. This drug stops the entry of aldosterone into the principle cells of the collecting duct and late distal tubule of the nephron, which prevents sodium and water retention.
Other examples of potassium-sparing diuretics include the epithelial sodium channel blockers triampterine and amiloride. These directly prevent sodium from entering the epithelial sodium (ENaC) channels, which are found in the apical membrane of the collecting tubule.
Osmotic diuretics inhibit the resabsorption 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