Pharmacological treatment of aldosterone excess

被引:29
作者
Deinum, Jaap [1 ]
Riksen, Niels P. [1 ]
Lenders, Jacques W. M. [1 ,2 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands
[2] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Internal Med 3, Dresden, Germany
关键词
Aldosterone; Mineralocorticoid receptor; Spironolactone; Eplerenone; Aldosterone synthase inhibitors; Calcium channel blockers; MINERALOCORTICOID-RECEPTOR ANTAGONIST; CHRONIC HEART-FAILURE; LEFT-VENTRICULAR HYPERTROPHY; CHRONIC KIDNEY-DISEASE; GERMAN CONNS REGISTRY; RANDOMIZED ALDACTONE EVALUATION; RENIN ESSENTIAL HYPERTENSION; CALCIUM-CHANNEL BLOCKADE; CORONARY-ARTERY-DISEASE; OBSTRUCTIVE SLEEP-APNEA;
D O I
10.1016/j.pharmthera.2015.07.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Primary aldosteronism, caused by autonomous secretion of aldosterone by the adrenals, is estimated to account for at least 5% of hypertension cases. Hypertension explains the considerable cardiovascular morbidity caused by aldosteronism only partly, calling for specific anti-aldosterone drugs. The pharmacology of aldosterone is complex due to high homology with other steroids, the resemblance of steroid receptors, and the common pathways of steroid synthesis. Classically, pharmacological treatment of aldosteronism relied on the mineralocorticoid receptor (MR) antagonist spironolactone, which is highly effective, but causes considerable, mainly sexual side-effects due to limited selectivity for the MR New agents have been developed or are being developed that aim at higher selectivity for MR antagonists (eplerenone, dihydropyridine-derived calcium channel blockers (CCB)), or inhibition of aldosterone synthesis. Eplerenone is less potent than spironolactone, but causes fewer adverse effects due to its selectivity for the MR. Non-steroidal MR antagonists have been developed from dihydropyridine CCBs, having lost their CCB activity and being highly selective for the MR. The first clinical studies with these drugs are underway. Aldosterone synthase inhibitors are an attractive alternative, but are prone to interference with cortisol synthesis due to the inhibition of 11-beta-hydroxylation, an essential step in both cortisol and aldosterone synthesis, and accumulation of mineralocorticoid precursors. In coming years clinical research will provide the answers as to which drugs and strategies to treat high-aldosterone states are the most effective. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:120 / 133
页数:14
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