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瑞米唑仑的兴起:药理学、临床疗效及安全性综述

The Rise of Remimazolam: A Review of Pharmacology, Clinical Efficacy, and Safety Profiles.

作者信息

Dessai Saiesh, Ninave Sanjot, Bele Amol

机构信息

Anesthesia, Datta Meghe Institute of Higher Education & Research, Wardha, IND.

出版信息

Cureus. 2024 Mar 30;16(3):e57260. doi: 10.7759/cureus.57260. eCollection 2024 Mar.

DOI:10.7759/cureus.57260
PMID:38686236
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11056802/
Abstract

Anesthesiologists often use benzodiazepines (BZDs) due to their remarkable amnestic and anxiolytic capabilities. Because of this, they are perfect for use during the perioperative phase, when patients' anxiety levels are already high. Remimazolam has replaced certain commonly used intravenous (IV) anesthetics due to its excellent safety profile, rapid onset of action, and short half-life. The four classes of BZDs, 2-keto-benzodiazepines, 3-hydroxy-benzodiazepines, triazolobenzodiazepines, and 7-nitro-benzodiazepines based on chemical structure, provide various levels of drowsiness, forgetfulness, and anxiolysis. Based on their elimination half-life, short-acting BZDs typically have a half-life ranging from one to 12 hours, e.g., oxazepam; intermediate-acting BZDs have an average elimination half-life of 12 to 40 hours, e.g., alprazolam; and long-acting BZDs have an average elimination half-life of more than 40 hours, e.g., diazepam. The chloride ion channel is conformationally shifted by the benzodiazepine molecule resulting in central nervous system (CNS) inhibition and hyperpolarization. Each type of benzodiazepine has a favored use. For example, diazepam is used to treat anxiety. Midazolam is used for its anxiolytic and anterograde amnestic effects during the perioperative phase. Anxiety and epilepsy are two conditions that lorazepam effectively treats. There are now phase II and III clinical studies investigating remimazolam. It is not sensitive to alterations in its surroundings and has a brief half-life so that it may be removed rapidly, even after extensive infusion. Being a soft drug means the body easily breaks it down via metabolism, which explains many features. Remimazolam is hydrolyzed into methanol and its carboxylic acid metabolite CNS 7054 by esterase metabolism. Therefore, remimazolam has a shorter onset time and faster recovery than other BZDs. Remimazolam is metabolized independently of any particular organ. Patients with hepatic and renal problems will not see any changes in metabolism or excretion since the drug's ester moiety makes it a substrate for general tissue esterase enzymes. Like its predecessor, midazolam, it has a high potential for addiction. Some side effects that could occur during infusion include headaches and drowsiness. In clinical trials, hypotension, respiratory depression, and bradycardia were noted in participants. BZDs are helpful when used in conjunction with anesthesia. Remimazolam stands out, thanks to its unique pharmacokinetics, pharmacodynamics, safety profile, and potential medical applications. Its desirable properties make it a potential surgical premedication and sedative in the critical care unit. Anesthesiologists and other doctors could have access to more consistent and safer medication. However, additional comprehensive clinical trials are necessary to understand remimazolam's advantages and disadvantages.

摘要

麻醉医生经常使用苯二氮䓬类药物(BZDs),因为它们具有显著的遗忘和抗焦虑能力。因此,它们非常适合在围手术期使用,此时患者的焦虑水平已经很高。瑞马唑仑因其出色的安全性、快速起效和短半衰期,已取代了某些常用的静脉麻醉药。根据化学结构,BZDs可分为四类:2-酮基苯二氮䓬类、3-羟基苯二氮䓬类、三唑苯二氮䓬类和7-硝基苯二氮䓬类,它们能产生不同程度的嗜睡、遗忘和抗焦虑作用。根据消除半衰期,短效BZDs的半衰期通常为1至12小时,例如奥沙西泮;中效BZDs的平均消除半衰期为12至40小时,例如阿普唑仑;长效BZDs的平均消除半衰期超过40小时,例如地西泮。苯二氮䓬分子会使氯离子通道发生构象变化,从而导致中枢神经系统(CNS)抑制和超极化。每种苯二氮䓬类药物都有其首选用途。例如,地西泮用于治疗焦虑症。咪达唑仑在围手术期用于其抗焦虑和顺行性遗忘作用。劳拉西泮可有效治疗焦虑症和癫痫。目前有关于瑞马唑仑的II期和III期临床研究。它对周围环境的变化不敏感,半衰期短,因此即使大量输注后也能迅速清除。作为一种软性药物意味着身体可以通过代谢轻松分解它,这解释了它的许多特性。瑞马唑仑通过酯酶代谢水解为甲醇及其羧酸代谢物CNS 7054。因此,与其他BZDs相比,瑞马唑仑起效时间更短,恢复更快。瑞马唑仑的代谢不依赖于任何特定器官。患有肝、肾问题的患者的代谢或排泄不会有任何变化,因为该药物的酯部分使其成为一般组织酯酶的底物。与它的前身咪达唑仑一样,它有很高的成瘾潜力。输注过程中可能出现的一些副作用包括头痛和嗜睡。在临床试验中,参与者出现了低血压、呼吸抑制和心动过缓。BZDs与麻醉联合使用时很有帮助。瑞马唑仑因其独特的药代动力学、药效学、安全性和潜在的医学应用而脱颖而出。其理想的特性使其成为潜在的手术前用药和重症监护病房的镇静剂。麻醉医生和其他医生可以使用更一致、更安全的药物。然而,需要进行更多全面的临床试验来了解瑞马唑仑的优缺点。

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