title: Comparison of agents that affect aldosterone action.
abstract: The first aldosterone blocker, spironolactone, initially was used as a diuretic but was accompanied by a significant amount of side effects that necessitated the withdrawal of the drug in a relevant number of patients. The discovery of the many receptor-mediated actions of aldosterone in several different organs greatly contributed to expand the indications of aldosterone blockers. Eplerenone was the second component of this class of drugs and differed from spironolactone because of its significantly better safety, albeit this was accompanied by a lower potency when used at equinumeric doses. Although these two drugs were being used in clinical practice, the epithelial sodium channel blockers, amiloride and triamterene, with a similar antialdosterone action, continued to be used in clinical practice in combination with thiazides and loop diuretics. New members of the third and fourth generation of mineralocorticoid receptor antagonists and aldosterone synthase inhibitors are in development. These new compounds, which include the new nonsteroidal mineralocorticoid-receptor antagonists and aldosterone synthase inhibitors, try to maintain adequate efficacy, avoiding the drawbacks of spironolactone and eplerenone. Ongoing studies will show the certainty of the capacities of these new compounds to override the virtues of the first mineralocorticoid-receptor spironolactone while avoiding the side effects leading so frequently to the withdrawal of the drug, including a significantly lower prevalence of hyperkalemia when chronic kidney disease is present.
authors.affiliation: Department of Pharmacology, School of Medicine, University Complutense, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Tamargo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Solini
authors.affiliation: Research Institute, Hypertension Unit, Hospital 12 de Octubre and Department of Public Health and Preventive Medicine, University Autonoma, Madrid, Spain. Electronic address: Ruilope@ad-hocbox.com.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Ruilope
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D062686:Epithelial Sodium Channel Blockers / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006929:Hyperaldosteronism / Q000188:drug therapy; D006947:Hyperkalemia / Q000139:chemically induced; D006973:Hypertension / Q000188:drug therapy; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D051436:Renal Insufficiency, Chronic / Q000150:complications; D016277:Ventricular Function, Left
chemical_list: D062686:Epithelial Sodium Channel Blockers; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D006854:Hydrocortisone
keywords: Aldosterone; aldosterone receptor antagonists; aldosterone synthase inhibitors; canrenone; eplerenone; heart failure; hyperaldosteronism; hypertension; spironolactone