title: Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone.
abstract: Spironolactone was first developed over 50 years ago as a potent mineralocorticoid receptor antagonist with undesirable side effects; it was followed a decade ago by eplerenone, which is less potent but much more mineralocorticoid receptor-specific. From a marginal role as a potassium-sparing diuretic, spironolactone has been shown to be an extraordinarily effective adjunctive agent in the treatment of progressive heart failure. Also, spironolactone is safe and protective in arterial hypertension, particularly in patients with so-called resistant hypertension. Eplerenone is the second oral aldosterone antagonist available for the treatment of arterial hypertension and heart failure. Treatment with eplerenone has been associated with decreased blood pressure and improved survival for patients with heart failure and reduced left ventricular ejection fraction. Due to the selectivity of eplerenone for the aldosterone receptor, severe adverse effects such as gynecomastia and vaginal bleeding seem to be less likely in patients who take eplerenone than in those who take spironolactone. The most common and potentially dangerous side effect of spironolactone--hyperkalemia--is also observed with eplerenone but the findings from clinical trials do not indicate more hyperkalemia induced drug withdrawals. Treatment with eplerenone should be initiated at a dosage of 25mg once daily and titrated to a target dosage of 50mg once daily preferably within 4 weeks. Serum potassium levels and renal function should be assessed prior to initiating eplerenone therapy, and periodic monitoring is recommended, especially in patients at high risk of developing hyperkalemia.
authors.affiliation: Division of Cardiology, University Clinic Golnik, Golnik, Slovenia.
authors.forename: Mitja
authors.initials: M
authors.lastname: Lainscak
authors.affiliation: Department of Heart and Great Vessels, Sapienza University, Rome, Italy. Electronic address: f.pelliccia@mclink.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pelliccia
authors.affiliation: IRCCS San Raffaele Pisana, Rome, Italy; Cardiovascular and Cell Sciences Research Institute, St. George's, University of London, London, UK.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rosano
authors.affiliation: IRCCS San Raffaele Pisana, Rome, Italy; Cardiovascular and Cell Sciences Research Institute, St. George's, University of London, London, UK.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Vitale
authors.affiliation: Department of Heart and Great Vessels, Sapienza University, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Schiariti
authors.affiliation: Department of Heart and Great Vessels, Sapienza University, Rome, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Greco
authors.affiliation: Istituto Clinico Cardiologico - GVM, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Speziale
authors.affiliation: Department of Heart and Great Vessels, Sapienza University, Rome, Italy; Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaudio
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D004347:Drug Interactions; D000077545:Eplerenone; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic; D013148:Spironolactone / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone
keywords: Aldosterone; Eplerenone; Mineralocorticoid receptors; Spironolactone