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mineralocorticoid antagonists used clinically include spironolactone (Aldactone) and eplerenone (Inspra). These drugs are competitive antagonists of the aldosterone receptor; that is, they bind to the receptor but do not activate it. When bound to the receptor, these drugs block the effects of endogenous mineralocorticoid (aldosterone) by preventing the aldosterone from binding to renal cells and other tissues. Consequently, spironolactone and eplerenone antagonize the normal physiologic effects of aldosterone, resulting in increased sodium and water excretion and decreased potassium excretion.

Spironolactone and eplerenone are used primarily as diuretics in treating hypertension and heart failure. These drugs are classified as potassium-sparing diuretics because they help increase sodium and water excretion without increasing the excretion of potassium (see Chapter 21). Spironolactone is also used to help diagnose hyperaldosteronism. The drug is given for several days to antagonize the effects of excessive aldosterone production. When the drug is discontinued, serum potassium levels will decrease sharply if hyperaldosteronism is present; that is, plasma potassium levels will fall when aldosterone is again permitted to increase potassium excretion.

As indicated above, mineralocorticoid antagonists, such as spironolactone and eplerenone, can help decrease the detrimental effects of aldosterone on the heart and vasculature. By blocking aldosterone receptors in cardiac and vascular cells, these drugs prevent adverse cellular changes (fibrosis, hypertrophy) that can contribute to hypertension, heart failure, and other cardiovascular diseases.27,40 Preliminary evidence suggests that mineralocorticoid receptor antagonist may help reduce the progression of these diseases, and future studies will help clarify how these drugs can be best used as part of the pharmacological regimen for patients with cardiovascular dysfunction.82

Mineralocorticoid antagonists may cause an increase in plasma potassium levels (hyperkalemia),which could be life-threatening if prolonged or severe.70 Spironolactone can also interfere with the function of the endogenous sex hormones, thereby producing side effects such as increased body hair,deepening of the voice, decreased libido, menstrual irregularities, and breast enlargement in men. It Appears, however, that eplerenone has a lower incidence of these sexual side effects, and this drug may preferentially suppress mineralocorticoid function without also affecting the sex hormones.81 Finally,mineralocorticoid antagonists can cause gastrointestinal disturbances (diarrhea, stomach pain, gastric ulcers), and spironolactone can also cause CNS effects(drowsiness, lethargy, confusion, headache).