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药物排石治疗的当前及新出现的药理学靶点

Current and emerging pharmacological targets for medical expulsive therapy.

作者信息

Lim Iris, Sellers Donna J, Chess-Williams Russ

机构信息

Centre for Urology Research, Faculty of Health Science & Medicine, Bond University, Gold Coast, QLD, Australia.

出版信息

Basic Clin Pharmacol Toxicol. 2022 Jan;130 Suppl 1:16-22. doi: 10.1111/bcpt.13613. Epub 2021 May 26.

DOI:10.1111/bcpt.13613
PMID:33991399
Abstract

The primary goals of medical expulsive therapy are to increase the rate of stone expulsion along the ureter to avoid ureteral obstruction and reduce ureteral colic and thus avoid the need for surgical and more invasive interventions. This review focussed on the findings from in vivo and in vitro animal and human studies that have investigated the pharmacological mechanisms controlling ureteral motility and their translation to current and potentially new clinically used drugs for increasing the rate of stone expulsion along the ureter. The complicated contractility profile of the ureter, which alters with age, tissue segment region, orientation and species contributes to the difficulty of interpreting studies on ureteral pharmacology, which translates to the complexity of discovering ideal drug targets for medical expulsive therapy. Nevertheless, the current drug classes clinically used for patients with stone lodgement include α -adrenoceptor antagonists, calcium channel blockers and NSAIDS, whilst there are promising targets for drug development that require further clinical investigations including the phosphodiesterase type 5 enzyme, β-adrenoceptors and 5-HT receptors.

摘要

药物排石治疗的主要目标是提高结石沿输尿管排出的速率,以避免输尿管梗阻,减轻输尿管绞痛,从而避免进行手术及其他侵入性干预。本综述聚焦于体内和体外动物及人体研究的结果,这些研究调查了控制输尿管蠕动的药理学机制,以及这些机制如何转化为当前及潜在的新型临床用药,以提高结石沿输尿管排出的速率。输尿管复杂的收缩特性会随年龄、组织节段区域、方向和物种而改变,这导致解释输尿管药理学研究存在困难,进而造成了为药物排石治疗寻找理想药物靶点的复杂性。尽管如此,目前临床上用于结石嵌顿患者的药物类别包括α-肾上腺素能受体拮抗剂、钙通道阻滞剂和非甾体抗炎药,同时还有一些有前景的药物研发靶点需要进一步的临床研究,包括5型磷酸二酯酶、β-肾上腺素能受体和5-羟色胺受体。

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