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Erschienen in: Clinical Research in Cardiology Supplements 1/2007

01.01.2007 | Klinische Pharmakologie

Aldosteron und Aldosteronrezeptorantagonisten in der Herzinsuffizienztherapie

verfasst von: Dr. T. Rau, T. Eschenhagen

Erschienen in: Clinical Research in Cardiology Supplements | Ausgabe 1/2007

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Zusammenfassung

Aldosteron und dem Aldosteronrezeptor können neben Effekten auf den Elektrolyt- und Wasserhaushalt weitere Rollen in der Pathophysiologie kardiovaskulärer Erkrankungen zugeschrieben werden. Diese Effekte betreffen z. B. Blutdruck (durch direkte Aldosteroneffekte auf Gefäße und ZNS), Hypertrophie und Remodeling. Mit Spironolacton und Eplerenon stehen 2 Aldosteronrezeptorantagonisten für den Dauergebrauch zur Verfügung, die ihre klinische Wirksamkeit in endpunktbasierten Studien gezeigt haben. Spironolacton hat zusätzlich zur antagonistischen Wirkung am Mineralokortikoidrezeptor Wirkungen am Testosteron- und Progesteronrezeptor, die zu endokrinen Nebenwirkungen führen können. Entsprechende UAW fehlen bei Eplerenon, das als selektiver Aldosteronrezeptorantagonist klassifiziert werden kann. Eplerenon hat eine kürzere Plasmahalbwertszeit als die aktiven Metabolite von Spironolacton. Eplerenon wird durch CYP3A4 metabolisiert, hier müssen pharmakokinetische Interaktionen bedacht werden. Wesentlich bei der Kombination von Aldosteronrezeptorantagonisten mit anderen prognoseverbessernden Substanzen in der Herzinsuffizienztherapie ist die Kontrolle der Kaliumspiegel und der Nierenfunktion. Die Dosierungsempfehlungen sollten unbedingt beachtet werden. Besonderer Aufmerksamkeit hinsichtlich der Entwicklung einer Hyperkaliämie bedürfen Patienten mit Einschränkung der Nierenfunktion. Aldosteronantagonisten sollten bei einer glomerulären Filtrationsrate unter 50 ml/min nicht eingesetzt werden.
Literatur
1.
Zurück zum Zitat Pitt B, Zannad F, Remme WJ et al. (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341: 709–717CrossRefPubMed Pitt B, Zannad F, Remme WJ et al. (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341: 709–717CrossRefPubMed
2.
Zurück zum Zitat Pitt B, Remme W, Zannad F et al. (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348: 1309–1321CrossRefPubMed Pitt B, Remme W, Zannad F et al. (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348: 1309–1321CrossRefPubMed
3.
Zurück zum Zitat Hoppe UC, Bohm M, Dietz R et al. (2005) Guidelines for therapy of chronic heart failure. Z Kardiol 94: 488–509CrossRefPubMed Hoppe UC, Bohm M, Dietz R et al. (2005) Guidelines for therapy of chronic heart failure. Z Kardiol 94: 488–509CrossRefPubMed
4.
Zurück zum Zitat Tait SA, Tait JF, Coghlan JP (2004) The discovery, isolation and identification of aldosterone: reflections on emerging regulation and function. Mol Cell Endocrinol 217: 1–21CrossRef Tait SA, Tait JF, Coghlan JP (2004) The discovery, isolation and identification of aldosterone: reflections on emerging regulation and function. Mol Cell Endocrinol 217: 1–21CrossRef
5.
Zurück zum Zitat Stockand JD (2002) New ideas about aldosterone signaling in epithelia. Am J Physiol Renal Physiol 282: F559–576PubMed Stockand JD (2002) New ideas about aldosterone signaling in epithelia. Am J Physiol Renal Physiol 282: F559–576PubMed
6.
Zurück zum Zitat Menard J (2004) The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol 217: 45–52CrossRefPubMed Menard J (2004) The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol 217: 45–52CrossRefPubMed
7.
Zurück zum Zitat Losel R, Schultz A, Wehling M (2004) A quick glance at rapid aldosterone action. Mol Cell Endocrinol 217: 137–141CrossRefPubMed Losel R, Schultz A, Wehling M (2004) A quick glance at rapid aldosterone action. Mol Cell Endocrinol 217: 137–141CrossRefPubMed
8.
Zurück zum Zitat Losel R, Schultz A, Boldyreff B, Wehling M (2004) Rapid effects of aldosterone on vascular cells: clinical implications. Steroids 69: 575–578CrossRefPubMed Losel R, Schultz A, Boldyreff B, Wehling M (2004) Rapid effects of aldosterone on vascular cells: clinical implications. Steroids 69: 575–578CrossRefPubMed
9.
Zurück zum Zitat Mihailidou AS, Funder JW (2005) Nongenomic effects of mineralocorticoid receptor activation in the cardiovascular system. Steroids 70: 347–351CrossRefPubMed Mihailidou AS, Funder JW (2005) Nongenomic effects of mineralocorticoid receptor activation in the cardiovascular system. Steroids 70: 347–351CrossRefPubMed
10.
Zurück zum Zitat Mihailidou AS, Mardini M, Funder JW (2004) Rapid, nongenomic effects of aldosterone in the heart mediated by epsilon protein kinase C. Endocrinology 145: 773–780CrossRefPubMed Mihailidou AS, Mardini M, Funder JW (2004) Rapid, nongenomic effects of aldosterone in the heart mediated by epsilon protein kinase C. Endocrinology 145: 773–780CrossRefPubMed
12.
Zurück zum Zitat Jaffe IZ, Mendelsohn ME (2005) Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ Res Jaffe IZ, Mendelsohn ME (2005) Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ Res
13.
Zurück zum Zitat Christ M, Wehling M, Kirsch E et al. (2005) Enhancement of beta-adrenergic cAMP-signaling by the mineralocorticoid receptor. Mol Cell Endocrinol 231: 23–31CrossRefPubMed Christ M, Wehling M, Kirsch E et al. (2005) Enhancement of beta-adrenergic cAMP-signaling by the mineralocorticoid receptor. Mol Cell Endocrinol 231: 23–31CrossRefPubMed
14.
Zurück zum Zitat Beggah A, Escoubet B, Puttini S et al. (2002) Reversible cardiac fibrosis and heart failure induced by conditional expression of an antisense mRNA of the mineralocorticoid receptor in cardiomyocytes. Proc Natl Acad Sci USA 99: 7160–7165CrossRefPubMed Beggah A, Escoubet B, Puttini S et al. (2002) Reversible cardiac fibrosis and heart failure induced by conditional expression of an antisense mRNA of the mineralocorticoid receptor in cardiomyocytes. Proc Natl Acad Sci USA 99: 7160–7165CrossRefPubMed
15.
Zurück zum Zitat Berger S, Bleich M, Schmid W et al. (1998) Mineralocorticoid receptor knockout mice: pathophysiology of Na+ metabolism. Proc Natl Acad Sci USA 95: 9424–9429CrossRefPubMed Berger S, Bleich M, Schmid W et al. (1998) Mineralocorticoid receptor knockout mice: pathophysiology of Na+ metabolism. Proc Natl Acad Sci USA 95: 9424–9429CrossRefPubMed
16.
Zurück zum Zitat Lecain E, Yang TH, Tran Ba Huy P (2003) Steroidogenic enzyme expression in the rat cochlea. Acta Otolaryngol 123: 187–191CrossRefPubMed Lecain E, Yang TH, Tran Ba Huy P (2003) Steroidogenic enzyme expression in the rat cochlea. Acta Otolaryngol 123: 187–191CrossRefPubMed
17.
Zurück zum Zitat Gomez-Sanchez EP, Ahmad N, Romero DG, Gomez-Sanchez CE (2005) Is aldosterone synthesized within the rat brain? Am J Physiol Endocrinol Metab 288: E342–346CrossRefPubMed Gomez-Sanchez EP, Ahmad N, Romero DG, Gomez-Sanchez CE (2005) Is aldosterone synthesized within the rat brain? Am J Physiol Endocrinol Metab 288: E342–346CrossRefPubMed
18.
Zurück zum Zitat Funder JW (2004) Cardiac synthesis of aldosterone: going, going, gone ...? Endocrinology 145: 4793–4795CrossRefPubMed Funder JW (2004) Cardiac synthesis of aldosterone: going, going, gone ...? Endocrinology 145: 4793–4795CrossRefPubMed
19.
Zurück zum Zitat Gomez-Sanchez EP, Ahmad N, Romero DG, Gomez-Sanchez CE (2004) Origin of aldosterone in the rat heart. Endocrinology 145: 4796–4802CrossRefPubMed Gomez-Sanchez EP, Ahmad N, Romero DG, Gomez-Sanchez CE (2004) Origin of aldosterone in the rat heart. Endocrinology 145: 4796–4802CrossRefPubMed
20.
Zurück zum Zitat Tsutamoto T, Wada A, Maeda K et al. (2003) Transcardiac gradient of aldosterone before and after spironolactone in patients with congestive heart failure. J Cardiovasc Pharmacol 41 [Suppl 1]: S19–22 Tsutamoto T, Wada A, Maeda K et al. (2003) Transcardiac gradient of aldosterone before and after spironolactone in patients with congestive heart failure. J Cardiovasc Pharmacol 41 [Suppl 1]: S19–22
21.
Zurück zum Zitat Tsutamoto T, Wada A, Maeda K et al. (2000) Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure. J Am Coll Cardiol 36: 838–844CrossRefPubMed Tsutamoto T, Wada A, Maeda K et al. (2000) Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure. J Am Coll Cardiol 36: 838–844CrossRefPubMed
22.
Zurück zum Zitat Mizuno Y, Yoshimura M, Yasue H et al. (2001) Aldosterone production is activated in failing ventricle in humans. Circulation 103: 72–77PubMed Mizuno Y, Yoshimura M, Yasue H et al. (2001) Aldosterone production is activated in failing ventricle in humans. Circulation 103: 72–77PubMed
23.
Zurück zum Zitat Spat A, Hunyady L (2004) Control of aldosterone secretion: a model for convergence in cellular signaling pathways. Physiol Rev 84: 489–539CrossRefPubMed Spat A, Hunyady L (2004) Control of aldosterone secretion: a model for convergence in cellular signaling pathways. Physiol Rev 84: 489–539CrossRefPubMed
24.
Zurück zum Zitat Lisurek M, Bernhardt R (2004) Modulation of aldosterone and cortisol synthesis on the molecular level. Mol Cell Endocrinol 215: 149–159CrossRefPubMed Lisurek M, Bernhardt R (2004) Modulation of aldosterone and cortisol synthesis on the molecular level. Mol Cell Endocrinol 215: 149–159CrossRefPubMed
25.
Zurück zum Zitat Okubo S, Niimura F, Nishimura H et al. (1997) Angiotensin-independent mechanism for aldosterone synthesis during chronic extracellular fluid volume depletion. J Clin Invest 99: 855–860PubMed Okubo S, Niimura F, Nishimura H et al. (1997) Angiotensin-independent mechanism for aldosterone synthesis during chronic extracellular fluid volume depletion. J Clin Invest 99: 855–860PubMed
26.
Zurück zum Zitat Jorde UP, Vittorio T, Katz SD et al. (2002) Elevated plasma aldosterone levels despite complete inhibition of the vascular angiotensin-converting enzyme in chronic heart failure. Circulation 106: 1055–1057CrossRefPubMed Jorde UP, Vittorio T, Katz SD et al. (2002) Elevated plasma aldosterone levels despite complete inhibition of the vascular angiotensin-converting enzyme in chronic heart failure. Circulation 106: 1055–1057CrossRefPubMed
27.
Zurück zum Zitat Pascual-Le Tallec L, Lombes M (2005) The mineralocorticoid receptor: a journey exploring its diversity and specificity of action. Mol Endocrinol 19(9): 2211–2221CrossRefPubMed Pascual-Le Tallec L, Lombes M (2005) The mineralocorticoid receptor: a journey exploring its diversity and specificity of action. Mol Endocrinol 19(9): 2211–2221CrossRefPubMed
28.
Zurück zum Zitat Rogerson FM, Brennan FE, Fuller PJ (2004) Mineralocorticoid receptor binding, structure and function. Mol Cell Endocrinol 217: 203–212CrossRefPubMed Rogerson FM, Brennan FE, Fuller PJ (2004) Mineralocorticoid receptor binding, structure and function. Mol Cell Endocrinol 217: 203–212CrossRefPubMed
29.
Zurück zum Zitat Funder JW, Pearce PT, Smith R, Campbell J (1989) Vascular type I aldosterone binding sites are physiological mineralocorticoid receptors. Endocrinology 125: 2224–2226PubMed Funder JW, Pearce PT, Smith R, Campbell J (1989) Vascular type I aldosterone binding sites are physiological mineralocorticoid receptors. Endocrinology 125: 2224–2226PubMed
30.
Zurück zum Zitat Seckl JR (2004) 11beta-hydroxysteroid dehydrogenases: changing glucocorticoid action. Curr Opin Pharmacol 4: 597–602CrossRefPubMed Seckl JR (2004) 11beta-hydroxysteroid dehydrogenases: changing glucocorticoid action. Curr Opin Pharmacol 4: 597–602CrossRefPubMed
31.
Zurück zum Zitat Lombes M, Kenouch S, Souque A et al. (1994) The mineralocorticoid receptor discriminates aldosterone from glucocorticoids independently of the 11 beta-hydroxysteroid dehydrogenase. Endocrinology 135: 834–840CrossRefPubMed Lombes M, Kenouch S, Souque A et al. (1994) The mineralocorticoid receptor discriminates aldosterone from glucocorticoids independently of the 11 beta-hydroxysteroid dehydrogenase. Endocrinology 135: 834–840CrossRefPubMed
32.
Zurück zum Zitat Farman N, Rafestin-Oblin ME (2001) Multiple aspects of mineralocorticoid selectivity. Am J Physiol Renal Physiol 280: F181–192PubMed Farman N, Rafestin-Oblin ME (2001) Multiple aspects of mineralocorticoid selectivity. Am J Physiol Renal Physiol 280: F181–192PubMed
33.
Zurück zum Zitat Hellal-Levy C, Couette B, Fagart J et al. (1999) Specific hydroxylations determine selective corticosteroid recognition by human glucocorticoid and mineralocorticoid receptors. FEBS Lett 464: 9–13CrossRefPubMed Hellal-Levy C, Couette B, Fagart J et al. (1999) Specific hydroxylations determine selective corticosteroid recognition by human glucocorticoid and mineralocorticoid receptors. FEBS Lett 464: 9–13CrossRefPubMed
34.
Zurück zum Zitat Brilla CG, Pick R, Tan LB et al. (1990) Remodeling of the rat right and left ventricles in experimental hypertension. Circ Res 67: 1355–1364PubMed Brilla CG, Pick R, Tan LB et al. (1990) Remodeling of the rat right and left ventricles in experimental hypertension. Circ Res 67: 1355–1364PubMed
35.
Zurück zum Zitat Brilla CG, Matsubara LS, Weber KT (1993) Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. Am J Cardiol 71: 12A–16ACrossRefPubMed Brilla CG, Matsubara LS, Weber KT (1993) Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. Am J Cardiol 71: 12A–16ACrossRefPubMed
36.
37.
Zurück zum Zitat Hostetter TH, Ibrahim HN (2003) Aldosterone in chronic kidney and cardiac disease. J Am Soc Nephrol 14: 2395–2401CrossRefPubMed Hostetter TH, Ibrahim HN (2003) Aldosterone in chronic kidney and cardiac disease. J Am Soc Nephrol 14: 2395–2401CrossRefPubMed
38.
Zurück zum Zitat Rocha R, Rudolph AE, Frierdich GE et al. (2002) Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 283: H1802–1810PubMed Rocha R, Rudolph AE, Frierdich GE et al. (2002) Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 283: H1802–1810PubMed
39.
Zurück zum Zitat Rocha R, Funder JW (2002) The pathophysiology of aldosterone in the cardiovascular system. Ann N Y Acad Sci 970: 89–100PubMed Rocha R, Funder JW (2002) The pathophysiology of aldosterone in the cardiovascular system. Ann N Y Acad Sci 970: 89–100PubMed
40.
Zurück zum Zitat Suzuki G, Morita H, Mishima T et al. (2002) Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation 106: 2967–2972CrossRefPubMed Suzuki G, Morita H, Mishima T et al. (2002) Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure. Circulation 106: 2967–2972CrossRefPubMed
41.
Zurück zum Zitat Fraccarollo D, Galuppo P, Schmidt I et al. (2005) Additive amelioration of left ventricular remodeling and molecular alterations by combined aldosterone and angiotensin receptor blockade after myocardial infarction. Cardiovasc Res 67: 97–105CrossRefPubMed Fraccarollo D, Galuppo P, Schmidt I et al. (2005) Additive amelioration of left ventricular remodeling and molecular alterations by combined aldosterone and angiotensin receptor blockade after myocardial infarction. Cardiovasc Res 67: 97–105CrossRefPubMed
42.
Zurück zum Zitat Fraccarollo D, Galuppo P, Hildemann S et al. (2003) Additive improvement of left ventricular remodeling and neurohormonal activation by aldosterone receptor blockade with eplerenone and ACE inhibition in rats with myocardial infarction. J Am Coll Cardiol 42: 1666–1173CrossRefPubMed Fraccarollo D, Galuppo P, Hildemann S et al. (2003) Additive improvement of left ventricular remodeling and neurohormonal activation by aldosterone receptor blockade with eplerenone and ACE inhibition in rats with myocardial infarction. J Am Coll Cardiol 42: 1666–1173CrossRefPubMed
43.
Zurück zum Zitat Qin W, Rudolph AE, Bond BR et al. (2003) Transgenic model of aldosterone-driven cardiac hypertrophy and heart failure. Circ Res 93: 69–76CrossRefPubMed Qin W, Rudolph AE, Bond BR et al. (2003) Transgenic model of aldosterone-driven cardiac hypertrophy and heart failure. Circ Res 93: 69–76CrossRefPubMed
44.
Zurück zum Zitat Funder JW, Pearce PT, Myles K, Roy LP (1990) Apparent mineralocorticoid excess, pseudohypoaldosteronism, and urinary electrolyte excretion: toward a redefinition of mineralocorticoid action. Faseb J 4: 3234–3238PubMed Funder JW, Pearce PT, Myles K, Roy LP (1990) Apparent mineralocorticoid excess, pseudohypoaldosteronism, and urinary electrolyte excretion: toward a redefinition of mineralocorticoid action. Faseb J 4: 3234–3238PubMed
45.
46.
Zurück zum Zitat Rossi GP, Di Bello V, Ganzaroli C et al. (2002) Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Hypertension 40: 23–27CrossRefPubMed Rossi GP, Di Bello V, Ganzaroli C et al. (2002) Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Hypertension 40: 23–27CrossRefPubMed
47.
Zurück zum Zitat Young WF Jr (2003) Minireview: primary aldosteronism – changing concepts in diagnosis and treatment. Endocrinology 144: 2208–2213CrossRefPubMed Young WF Jr (2003) Minireview: primary aldosteronism – changing concepts in diagnosis and treatment. Endocrinology 144: 2208–2213CrossRefPubMed
48.
Zurück zum Zitat Stowasser M, Gordon RD (2004) Primary aldosteronism – careful investigation is essential and rewarding. Mol Cell Endocrinol 217: 33–39CrossRefPubMed Stowasser M, Gordon RD (2004) Primary aldosteronism – careful investigation is essential and rewarding. Mol Cell Endocrinol 217: 33–39CrossRefPubMed
49.
Zurück zum Zitat Sato A, Saruta T (2003) Aldosterone breakthrough during angiotensin-converting enzyme inhibitor therapy. Am J Hypertens 16: 781–788CrossRefPubMed Sato A, Saruta T (2003) Aldosterone breakthrough during angiotensin-converting enzyme inhibitor therapy. Am J Hypertens 16: 781–788CrossRefPubMed
50.
Zurück zum Zitat McKelvie RS, Yusuf S, Pericak D et al. (1999) Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 100: 1056–1064PubMed McKelvie RS, Yusuf S, Pericak D et al. (1999) Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 100: 1056–1064PubMed
51.
Zurück zum Zitat Farquharson CA, Struthers AD (2000) Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation 101: 594–597PubMed Farquharson CA, Struthers AD (2000) Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation 101: 594–597PubMed
52.
Zurück zum Zitat Prisant LM, Krum H, Roniker B et al. (2003) Can renin status predict the antihypertensive efficacy of eplerenone add-on therapy? J Clin Pharmacol 43: 1203–1210CrossRefPubMed Prisant LM, Krum H, Roniker B et al. (2003) Can renin status predict the antihypertensive efficacy of eplerenone add-on therapy? J Clin Pharmacol 43: 1203–1210CrossRefPubMed
53.
Zurück zum Zitat Pitt B, Reichek N, Willenbrock R et al. (2003) Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation 108: 1831–1838CrossRefPubMed Pitt B, Reichek N, Willenbrock R et al. (2003) Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation 108: 1831–1838CrossRefPubMed
54.
Zurück zum Zitat Hayashi M, Tsutamoto T, Wada A et al. (2003) Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation 107: 2559–2565CrossRefPubMed Hayashi M, Tsutamoto T, Wada A et al. (2003) Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation 107: 2559–2565CrossRefPubMed
55.
Zurück zum Zitat Modena MG, Aveta P, Menozzi A, Rossi R (2001) Aldosterone inhibition limits collagen synthesis and progressive left ventricular enlargement after anterior myocardial infarction. Am Heart J 141: 41–46CrossRefPubMed Modena MG, Aveta P, Menozzi A, Rossi R (2001) Aldosterone inhibition limits collagen synthesis and progressive left ventricular enlargement after anterior myocardial infarction. Am Heart J 141: 41–46CrossRefPubMed
56.
Zurück zum Zitat Pitt B, White H, Nicolau J et al. (2005) Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am College Cardiol 46: 425–431)CrossRef Pitt B, White H, Nicolau J et al. (2005) Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am College Cardiol 46: 425–431)CrossRef
57.
Zurück zum Zitat Beygui F, Collet JP, Benoliel JJ et al. (2006) High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction. Circulation 114: 2604–2610CrossRefPubMed Beygui F, Collet JP, Benoliel JJ et al. (2006) High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction. Circulation 114: 2604–2610CrossRefPubMed
58.
Zurück zum Zitat Zannad F, Alla F, Dousset B et al. (2000) Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation 102: 2700–2706PubMed Zannad F, Alla F, Dousset B et al. (2000) Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation 102: 2700–2706PubMed
59.
Zurück zum Zitat MacFadyen RJ, Barr CS, Struthers AD (1997) Aldosterone blockade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients. Cardiovasc Res 35: 30–34CrossRefPubMed MacFadyen RJ, Barr CS, Struthers AD (1997) Aldosterone blockade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients. Cardiovasc Res 35: 30–34CrossRefPubMed
60.
Zurück zum Zitat de Gasparo M, Joss U, Ramjoué HP et al. (1987) Three new epoxy-spirolactone derivatives: characterization in vivo and in vitro. J Pharm Exp Ther 240: 650–656 de Gasparo M, Joss U, Ramjoué HP et al. (1987) Three new epoxy-spirolactone derivatives: characterization in vivo and in vitro. J Pharm Exp Ther 240: 650–656
61.
Zurück zum Zitat Garthwaite SM, McMahon EG (2004) The evolution of aldosterone antagonists. Mol Cell Endocrinol 217: 27–31CrossRefPubMed Garthwaite SM, McMahon EG (2004) The evolution of aldosterone antagonists. Mol Cell Endocrinol 217: 27–31CrossRefPubMed
62.
Zurück zum Zitat Overdiek HW, Merkus FW (1987) The metabolism and biopharmaceutics of spironolactone in man. Rev Drug Metab Drug Interact 5: 273–302PubMed Overdiek HW, Merkus FW (1987) The metabolism and biopharmaceutics of spironolactone in man. Rev Drug Metab Drug Interact 5: 273–302PubMed
63.
Zurück zum Zitat Overdiek HW, Hermens WA, Merkus FW (1985) New insights into the pharmacokinetics of spironolactone. Clin Pharmacol Ther 38: 469–474PubMed Overdiek HW, Hermens WA, Merkus FW (1985) New insights into the pharmacokinetics of spironolactone. Clin Pharmacol Ther 38: 469–474PubMed
64.
Zurück zum Zitat Gardiner P, Schrode K, Quinlan D et al. (1989) Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites. J Clin Pharmacol 29: 342–347PubMed Gardiner P, Schrode K, Quinlan D et al. (1989) Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites. J Clin Pharmacol 29: 342–347PubMed
65.
Zurück zum Zitat Krause W, Karras J, Seifert W (1983) Pharmacokinetics of canrenone after oral administration of spironolactone and intravenous injection of canrenoate-K in healthy man. Eur J Clin Pharmacol 25: 449–453CrossRefPubMed Krause W, Karras J, Seifert W (1983) Pharmacokinetics of canrenone after oral administration of spironolactone and intravenous injection of canrenoate-K in healthy man. Eur J Clin Pharmacol 25: 449–453CrossRefPubMed
66.
Zurück zum Zitat Los LE, Colby HD (1994) Binding of spironolactone metabolites in vivo to renal mineralocorticoid receptors in guinea pigs. Pharmacology 48: 86–92PubMed Los LE, Colby HD (1994) Binding of spironolactone metabolites in vivo to renal mineralocorticoid receptors in guinea pigs. Pharmacology 48: 86–92PubMed
67.
Zurück zum Zitat Corvol P, Michaud A, Menard J et al. (1975) Antiandrogenic effects of spironolactones: mechanism of action. Endocrinology 97: 52–58PubMed Corvol P, Michaud A, Menard J et al. (1975) Antiandrogenic effects of spironolactones: mechanism of action. Endocrinology 97: 52–58PubMed
68.
Zurück zum Zitat de Gasparo M, Whitebread SE, Preiswerk G et al. (1989) Antialdosterones: Incidence and prevention of sexual side effects. J Steroid Biochem 32: 223–227CrossRefPubMed de Gasparo M, Whitebread SE, Preiswerk G et al. (1989) Antialdosterones: Incidence and prevention of sexual side effects. J Steroid Biochem 32: 223–227CrossRefPubMed
69.
Zurück zum Zitat Cook CS, Hauswald C, Oppermann JA, Schoenhard GL (1993) Involvement of cytochrome P-450IIIA in metabolism of potassium canrenoate to an epoxide: mechanism of inhibition of the epoxide formation by spironolactone and its sulfur-containing metabolite. J Pharmacol Exp Ther 266: 1–7PubMed Cook CS, Hauswald C, Oppermann JA, Schoenhard GL (1993) Involvement of cytochrome P-450IIIA in metabolism of potassium canrenoate to an epoxide: mechanism of inhibition of the epoxide formation by spironolactone and its sulfur-containing metabolite. J Pharmacol Exp Ther 266: 1–7PubMed
70.
Zurück zum Zitat Cook CS, Hauswald CL, Schoenhard GL et al. (1988) Difference in metabolic profile of potassium canrenoate and spironolactone in the rat: mutagenic metabolites unique to potassium canrenoate. Arch Toxicol 61: 201–212CrossRefPubMed Cook CS, Hauswald CL, Schoenhard GL et al. (1988) Difference in metabolic profile of potassium canrenoate and spironolactone in the rat: mutagenic metabolites unique to potassium canrenoate. Arch Toxicol 61: 201–212CrossRefPubMed
71.
Zurück zum Zitat Cook CS, Berry LM, Kim DH et al. (2002) Involvement of CYP3A in the metabolism of eplerenone in humans and dogs: differential metabolism by CYP3A4 and CYP3A5. Drug Metab Dispos 30: 1344–1351CrossRefPubMed Cook CS, Berry LM, Kim DH et al. (2002) Involvement of CYP3A in the metabolism of eplerenone in humans and dogs: differential metabolism by CYP3A4 and CYP3A5. Drug Metab Dispos 30: 1344–1351CrossRefPubMed
72.
Zurück zum Zitat Cook CS, Zhang L, Ames GB et al. (2003) Single- and repeated-dose pharmacokinetics of eplerenone, a selective aldosterone receptor blocker, in rats. Xenobiotica 33: 305–321CrossRefPubMed Cook CS, Zhang L, Ames GB et al. (2003) Single- and repeated-dose pharmacokinetics of eplerenone, a selective aldosterone receptor blocker, in rats. Xenobiotica 33: 305–321CrossRefPubMed
73.
Zurück zum Zitat Cook CS, Berry LM, Bible RH et al. (2003) Pharmacokinetics and metabolism of [14C]eplerenone after oral administration to humans. Drug Metab Dispos 31: 1448–1455CrossRefPubMed Cook CS, Berry LM, Bible RH et al. (2003) Pharmacokinetics and metabolism of [14C]eplerenone after oral administration to humans. Drug Metab Dispos 31: 1448–1455CrossRefPubMed
74.
Zurück zum Zitat Cook CS, Berry LM, Burton E (2004) Prediction of in vivo drug interactions with eplerenone in man from in vitro metabolic inhibition data. Xenobiotica 34: 215–228CrossRefPubMed Cook CS, Berry LM, Burton E (2004) Prediction of in vivo drug interactions with eplerenone in man from in vitro metabolic inhibition data. Xenobiotica 34: 215–228CrossRefPubMed
75.
Zurück zum Zitat Juurlink DN, Mamdani MM, Lee DS et al. (2004) Rates of hyperkalemia after publication of the randomized aldactone evaluation study. N Engl J Med 351: 543–551CrossRefPubMed Juurlink DN, Mamdani MM, Lee DS et al. (2004) Rates of hyperkalemia after publication of the randomized aldactone evaluation study. N Engl J Med 351: 543–551CrossRefPubMed
Metadaten
Titel
Aldosteron und Aldosteronrezeptorantagonisten in der Herzinsuffizienztherapie
verfasst von
Dr. T. Rau
T. Eschenhagen
Publikationsdatum
01.01.2007
Verlag
Springer-Verlag
Erschienen in
Clinical Research in Cardiology Supplements / Ausgabe 1/2007
Print ISSN: 1861-0706
Elektronische ISSN: 1861-0714
DOI
https://doi.org/10.1007/s11789-006-0025-x

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