Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis

Spironolacotone and eplerenone are mineralocorticoid-blocking agents used for their ability to block both the epithelial and non-epithelial actions of aldosterone. Spironolactone is a non-selective mineralocorticoid receptor antagonist with moderate affinity for both progesterone and androgen receptors. The latter property increases the likelihood of endocrine side effects with spironolactone including loss of libido, menstrual irregularities, gynecomastia and impotence. Eplerenone is a next generation aldosterone receptor antagonist selective for aldosterone receptors alone. This lesser affinity for progesterone and androgen receptors was arrived at by replacing the 17-alpha-thioacetyl group of spironolactone with a carbomethoxy group. Eplerenone is further distinguished from spironolactone by its shorter half-life and the fact that it does not have any active metabolites. Both eplerenone and spironolactone are effective antihypertensive agents and each has been shown to improve the morbidity and mortality of heart failure. Eplerenone or spironolactone use can increase serum potassium values and occasionally results in clinically relevant hyperkalemia. This is more apt to occur with spironolactone due to the very long half-life of several of its active metabolites.