Pharmacokinetics and Pharmacodynamics of Mineralocorticoid Blocking Agents and their Effects on Potassium Homeostasis
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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-α -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.
Key wordsmineralocorticoid receptor antagonism hyperkalemia class effect spironolactone eplerenone heart failure
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- 3.Mantero F, Lucarelli G. Aldosterone antagonists in hypertension and heart failure. Ann Endocrinol (Paris) 2000;61:52–60.Google Scholar
- 12.Shackleton CR, Wong NLM, Sutton RA. Distal (potassium-sparing) diuretics. In: Dirks JH, Sutton RAL, eds. Diuretics: Physiology, Pharmacology and Clinical UsePhiladelphia: WB Saunders, 1986:117.Google Scholar
- 14.Merkus FWHM, Overdiek JWPM, Cilissen J, et al. Pharmacokinetics of spironolactone after a single dose: Evaluation of the true canrenone serum concentrations during 24 hours. Clin Exp Hypertens 1983;[A]5:249.Google Scholar
- 21.Ravis WR, Reid S, Roniker B, Sica DA. Pharmacokinetics of eplerenone after single and multiple dosing in subjects with and without renal impairment. Journal of Clinical Pharmacology (in press).Google Scholar
- 23.Tolbert DS, Reid SE, Roniker B. Pharmacokinetics of eplerenone in special populations. Pharmacotherapy2002;22:1332.Google Scholar
- 24.Tolbert DS, Reid SE, Roniker B. Pharmacokinetics of eplerenone coadministered with other medications. Pharmacotherapy2002;22:1331.Google Scholar
- 36.Epstein M, Buckalew V, Martinez F, et al. Antiproteinuric efficacy of eplerenone, enalapril, and eplerenone/enalapril combination in diabetic hypertensives with microalbuminuria. Am J Hypertens 2002;15(Suppl 1):A24.Google Scholar
- 37.The RALES Investigators. Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (The Randomized Aldactone Evaluation Study [RALES]). Am J Cardiol 1996;78:902–907.Google Scholar
- 38.Sica DA. Eplerenone and serum potassium change—relationship to renal function. Am J Hypertens 2003:16(Suppl 1):A100.Google Scholar
- 40.Sica DA, Hess M. Aldosterone receptor antagonism: Interface with hyperkalemia in heart failure. Cong Heart Fail 2004;10:259–264.Google Scholar