Spironolactone is used as a diuretic to remove the excess fluid caused by congestive heart failure, cirrhosis of the liver, and kidney disease. It can also be used to treat elevated blood pressure in combination with other drugs and in resistant cases of low potassium (hypokalemia). Spironolactone is also used to counteract the effects of excessive adrenal aldosterone production. Aldosterone overproduction can occur from a tumor in the adrenal gland, or when enlarged adrenal glands produce an excessive amount of aldosterone.
Spironolactone blocks the effect of aldosterone in the kidneys to increase excretion of sodium and water in the urine while conserving potassium. In conjunction with thiazide or loop diuretics, spironolactone reduces the overall fluid volume in the body, which helps to control symptoms of liver disease, heart disease, and kidney disease.
The RAA system is the complex mechanism by which the kidneys control the cardiovascular system. The system goes awry in patients with heart failure; in these persons, the decreased renal blood flow is not due to low blood volume but to a heart pump that is not working efficiently. ACE inhibitors block the conversion of vasoconstrictor angiotensin I to the much more potent angiotensin II, also blocking the production of the sodium-retaining hormone aldosterone. This production is only transiently suppressed, thus allowing aldosterone production to "escape" the effects of the ACE inhibitors.
Spironolactone is a specialized antagonist of aldosterone. It acts as a competitive binding agent at the aldosterone receptor site in the distal convoluted renal tubules, preventing the formation of a protein important in the sodium-potassium exchange in the kidneys. This action causes increased amounts of water and sodium to be excreted while potassium is conserved.