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重新考虑醛固酮受体阻断策略的时机:非甾体类醛固酮受体阻滞剂的出现。

The Time to Reconsider Mineralocorticoid Receptor Blocking Strategy: Arrival of Nonsteroidal Mineralocorticoid Receptor Blockers.

机构信息

Division of Nephrology, Endocrinology and Vascular Medicine, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.

Katta General Hospital, Shiroishi, Miyagi, Japan.

出版信息

Curr Hypertens Rep. 2022 Jul;24(7):215-224. doi: 10.1007/s11906-022-01177-6. Epub 2022 Apr 30.

Abstract

PURPOSE OF REVIEW

The study aims to verify the advantages of nonsteroidal mineralocorticoid receptor blockers (MRBs) in the management of hypertension and cardiovascular and renal diseases, comparing with conventional MRBs.

RECENT FINDINGS

Based on the unique structures, the nonsteroidal MRBs have higher selectivity for mineralocorticoid receptors (MRs) and show no agonist activity for major steroid hormone receptors in contrast to steroidal MRBs. Today, there are two nonsteroidal MRBs, esaxerenone and finerenone, which completed phase 3 clinical trials. Series of clinical trials have shown that both agents achieve similar MR blockade with smaller doses as compared with steroidal MRBs, but have no off-target side effect such as gynecomastia. Esaxerenone has persistent blood pressure-lowering effects in various hypertensive populations, including essential hypertension and those with diabetes and/or chronic kidney disease, while finerenone has demonstrated reduction of the cardiovascular risk rather than blood pressure in patients with diabetes and chronic kidney disease. Nonsteroidal MRBs are a more refined agent which contributes to appropriate MR blocking with minimized unpleasant adverse effects.

摘要

目的综述

本研究旨在比较非甾体类盐皮质激素受体阻滞剂(MRBs)与传统甾体类 MRBs 相比,在高血压及心血管和肾脏疾病治疗方面的优势。

最近的发现

非甾体类 MRBs 基于其独特的结构,对盐皮质激素受体(MRs)具有更高的选择性,且与甾体类 MRBs 不同,对主要甾体激素受体没有激动活性。目前有两种非甾体类 MRBs,依普利酮和非奈利酮,已完成 3 期临床试验。一系列临床试验表明,这两种药物的 MR 阻断作用与甾体类 MRBs 相似,但没有后者那样的脱靶副作用,如男性乳房发育。依普利酮在包括原发性高血压、糖尿病和/或慢性肾脏病在内的各种高血压人群中均具有持续的降压作用,而非奈利酮则在糖尿病和慢性肾脏病患者中显示出降低心血管风险而非降低血压的作用。非甾体类 MRBs 是一种更精细的药物,可在最小化不良副作用的情况下实现适当的 MR 阻断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e25/9300503/937d29199801/11906_2022_1177_Fig1_HTML.jpg

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