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索利那新治疗膀胱功能障碍:是否存在痴呆或认知障碍的风险?

Treatment of bladder dysfunction with solifenacin: is there a risk of dementia or cognitive impairment?

机构信息

Laboratório de Neuropsicofarmacologia, Núcleo de Pesquisa e Desenvolvimentos de Medicamentos, Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil.

Departamento de Urologia, Hospital Geral de Fortaleza, Fortaleza, CE, Brasil.

出版信息

Braz J Med Biol Res. 2022 Jan 25;55:e11721. doi: 10.1590/1414-431X2021e11721. eCollection 2022.

Abstract

The use of bladder antimuscarinics is very common in the elderly. However, recent population-based studies that assessed the use of anticholinergics or bladder antimuscarinics showed an increased risk of dementia when these drugs were used for a prolonged period. Several of these population-based studies included patients who used solifenacin, which is a bladder antimuscarinic released in 2005 with the prospect of being a more selective antimuscarinic for M3 receptors (M3R), which could make it a safer drug when trying to avoid unwanted effects of older bladder antimuscarinics such as oxybutynin, especially with regard to changes in cognition. Since the various bladder antimuscarinics have distinct pharmacological characteristics, such as in the ability to penetrate the blood-brain barrier, in selectivity for muscarinic receptors, and in brain efflux mechanisms, their effects on the central nervous system (CNS) may vary. Solifenacin was the drug selected in this review, which aims to describe the results of several articles published in recent years reporting the effects of solifenacin on cognition or the risk of dementia development. Although preclinical studies show that solifenacin can also act on brain M1 receptors (M1R), short-term clinical studies have shown it to be safe for cognition. However, there are no long-term randomized studies that prove the safety of this drug for the CNS. Thus, until the safety of solifenacin has been established by long-term studies, it seems advisable to avoid prolonged use of this drug in elderly patients.

摘要

在老年人中,使用膀胱抗毒蕈碱药物非常常见。然而,最近的基于人群的研究评估了抗胆碱能药物或膀胱抗毒蕈碱药物的使用情况,发现这些药物长期使用会增加痴呆的风险。这些基于人群的研究中有几项包括使用索利那新的患者,索利那新是一种于 2005 年推出的膀胱抗毒蕈碱药物,有望成为对 M3 受体(M3R)更具选择性的抗毒蕈碱药物,这可以使其在避免使用其他较老的膀胱抗毒蕈碱药物(如奥昔布宁)时产生的不良影响方面更安全,特别是在认知方面。由于各种膀胱抗毒蕈碱药物具有不同的药理学特性,例如穿透血脑屏障的能力、对毒蕈碱受体的选择性以及脑外排机制,因此它们对中枢神经系统(CNS)的影响可能会有所不同。本文选择了索利那新作为研究药物,旨在描述近年来发表的几篇报告索利那新对认知或痴呆发展风险影响的文章的结果。虽然临床前研究表明索利那新也可以作用于大脑 M1 受体(M1R),但短期临床研究表明它对认知是安全的。然而,目前尚无长期随机研究证明该药物对 CNS 的安全性。因此,在长期研究确定索利那新的安全性之前,似乎明智的做法是避免老年患者长期使用这种药物。

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