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Different inverse agonist activities ofbeta-adrenergic receptor antagonists-pharmacologicalcharacterization and therapeutical implicationsin the treatment of chronic heart failure

机译:不同逆激动剂活性的β-肾上腺素能受体拮抗剂 - 药理特征和治疗意义治疗慢性心力衰竭

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The treatment of chronic heart failure with most beta-adrenergic receptor (p-AR) antagonists leads to an improvement of symptoms and left ventricular function. However, only metoprolol, bisoprolol and carvedilol have been shown to reduce mortality in these patients. Bucindolol did not reduce mortality and xamoterol even increased it. These differences may be related to different inverse agonist or partial agonist activity of P-AR antagonists. This review focusses on the determination of different intrinsic activity of the mentioned beta-AR antagonists in the human myocardium. Furthermore, the clinical impact of these differences is examined, in this regard, the effect of the different beta-AR antagonists on beta-AR regulation, minimum heart rate and exercise tolerance, as well as prognosis, is highlighted. It is concluded that the degree of inverse agonism of a beta-AR antagonist determines the degree of beta-AR resensitization, reduction of minimum heart rate, improvement of exercise tolerance and possibly also improvement of prognosis of patients with chronic heart failure.
机译:慢性心脏衰竭与大多数β-肾上腺素能受体(P-AR)拮抗剂导致的症状的改善和左室功能的处理。然而,只有美托洛尔,比索洛尔和卡维地洛已经证明,以减少在这些患者的死亡率。布新并没有降低死亡率和扎莫特罗甚至增加它。这些差异可能与不同的反向激动剂或P-AR拮抗剂的部分激动剂活性。在人类心肌提到的β-AR拮抗剂的不同内在活性的测定这次审查主要论点集中。此外,这些差异的临床影响进行检查,在这方面,对β-AR调节,最小的心脏速率和运动耐受力,以及预后不同的β-AR拮抗剂的作用,突出显示。结论:β-AR拮抗剂逆激动的程度决定的β-AR复敏,降低最低心脏率,运动耐量的改善,可能也改善患者的慢性心脏衰竭预后的程度。

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