| Aldosterone antagonists in hypertension and heart failure. | |
| | |
MedLine Citation:
|
PMID: 10790593 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Spironolactone, a competitive aldosterone receptor antagonist (ARA), has traditionally been the treatment of first choice in idiopathic hyperaldosteronism (IHA) and for preoperative management of aldosterone producing adenoma (APA). Spironolactone is partially absorbed, is extensively metabolized mainly by the liver and its therapeutic properties are attributable to active metabolite canrenone. At therapeutic doses of 25 to 400 mg per day, spironolactone effectively controls blood pressure and hypokalemia in the majority of cases. Endocrine side effect are often associated and mainly consist of gynecomastia, decreased libido and impotence in man and menstrual irregularities in women. Canrenone and the K+ salt of canrenoate are also in clinical use: they avoid the formation of intermediate products with anti-androgenic and progestational actions, resulting in a decreased incidence of side effects. Furthermore, a relatively new selective ARA compound (eplerenone) with reduced affinity for androgen and progesterone receptors, is currently undergoing clinical trials. In essential hypertension aldosterone can contribute to hypertension and increases the incidence of myocardial hypertrophy and cardiovascular events. On the other hand, inhibition of Renin-Angiotensin-Aldosterone System (RAAS) is associated with a decrease in blood pressure, with a regression of left ventricular hypertrophy and a reduction of target organ damage. Thus, ARA have been proposed as complementary treatment associated to ACE inhibitors and angiotensin receptor antagonists. Aldosterone is also known to play an important role in pathophysiolgy of congestive heart failure (CHF). In vitro and in vivo evidences suggest that aldosterone promotes myocardial fibrosis. This effect reflects direct, extra-epithelial actions of aldosterone via cardiac MR which are counteracted by ARAs in animal models. The RAAS is chronically activated in CHF. Non potassium-sparing diuretics further stimulate the RAAS and cause hypokalemia. Thus, use of ARAs in CHF was first proposed to correct potassium and magnesium depletion. At present ARAs are indicated in the management of primary hyperaldosteronism, in oedematous conditions in patients with CHF, in cirrhosis of the liver accompanied by oedema and ascites, in essential hypertension and in hypokalemic states. Its indication as adjunctive therapy of heart failure is currently under investigation. In fact, it is well known that even high doses of ACE inhibitors may not completely suppress the RAAS; aldosterone 'escape' may occur through non angiotensin II dependent mechanisms. Addition of spironolactone to an ACE inhibitor causes marked diuresis and symptomatic improvement. During the last few years, the RALES study (Randomized Aldactone Evaluation Study) was organized to explore the efficacy of combination therapy with spironolactone and ACE inhibitor in patients with CHF, class III or IV NYHA. The study was stopped 18 months early because the results were so statistically and clinically significant that it would be unethical to continue the trial. It is reported a 30 percent decrease in mortality and hospitalisation for cardiac causes in spironolactone-treated group vs placebo group. |
| | |
Authors:
|
F Mantero; G Lucarelli |
Related Documents
:
|
8175163 - Diurnal blood pressure variation and hormonal correlates in fatal familial insomnia. 21823743 - Contact pressure in the facet joint during sagittal bending of the cadaveric cervical s... 3967463 - Potentiation of cardiac vagal action by cold. |
Publication Detail:
|
Type: Journal Article; Review |
Journal Detail:
|
Title: Annales d'endocrinologie Volume: 61 ISSN: 0003-4266 ISO Abbreviation: Ann. Endocrinol. (Paris) Publication Date: 2000 Feb |
Date Detail:
|
Created Date: 2000-06-27 Completed Date: 2000-06-27 Revised Date: 2009-11-03 |
Medline Journal Info:
|
Nlm Unique ID: 0116744 Medline TA: Ann Endocrinol (Paris) Country: FRANCE |
Other Details:
|
Languages: eng Pagination: 52-60 Citation Subset: IM |
Affiliation:
|
Division of Endocrinology. Department of Internal Medecine, University of Ancona, Italy. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aldosterone
/
biosynthesis,
pharmacology,
physiology Aldosterone Antagonists / therapeutic use* Animals Female Heart Failure / drug therapy*, etiology, physiopathology Humans Hypertension / drug therapy*, etiology, physiopathology Male Receptors, Aldosterone / antagonists & inhibitors |
| Chemical | |
Reg. No./Substance:
|
0/Aldosterone Antagonists; 0/Receptors, Aldosterone; 52-39-1/Aldosterone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Therapeutic applications of angiotensin II receptor antagonists.
Next Document: Experimental angiogenesis : strategy for the functional study of the transcription factors of the Et...