Brull Sorin J, Naguib Mohamed
Department of Anesthesiology, Mayo Clinic College of Medicine, Mayo Clinic Hospital, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Drug Des Devel Ther. 2009 Sep 21;3:119-29. doi: 10.2147/dddt.s3868.
Despite the significant improvements in the pharmacology of muscle relaxants in the past six decades, the search for the ideal muscle relaxant continues, mainly because of the incomplete efficacy and persistent side effects associated with their antagonism. Clinical concerns remain about the residual paralysis and hemodynamic side effects associated with the classic pharmacologic reversal agents, the acetylcholinesterase inhibitors. Although the development of the "ideal muscle relaxant" remains illusory, pharmacologic advancements hold promise for improved clinical care and patient safety. Recent clinical advances include the development of short-acting nondepolarizing muscle relaxant agents that have fast onset and a very rapid metabolism that allows reliable and complete recovery; and the development of selective, "designer" reversal agents that are specific for a single drug or class of drugs. This article reviews recent developments in the pharmacology of these selective reversal agents: plasma cholinesterases, cysteine, and sugammadex. Although each of the selective reversal agents is specific in its substrate, the clinical use of the combination of muscle relaxant with its specific reversal agent will allow much greater intraoperative titrating ability, decreased side effect profile, and may result in a decreased incidence of postoperative residual paralysis and improved patient safety.
尽管在过去六十年中肌肉松弛剂的药理学有了显著进步,但对理想肌肉松弛剂的探索仍在继续,主要是因为其拮抗作用存在疗效不完全和副作用持续的问题。临床仍关注与经典药理学拮抗剂乙酰胆碱酯酶抑制剂相关的残余麻痹和血流动力学副作用。尽管“理想肌肉松弛剂”的研发仍然遥不可及,但药理学进展有望改善临床护理和患者安全。近期的临床进展包括开发起效快、代谢非常迅速从而能实现可靠且完全恢复的短效非去极化肌肉松弛剂;以及开发针对单一药物或一类药物的选择性“定制”拮抗剂。本文综述了这些选择性拮抗剂(血浆胆碱酯酶、半胱氨酸和舒更葡糖)药理学的最新进展。尽管每种选择性拮抗剂都有其特定的作用底物,但肌肉松弛剂与其特定拮抗剂联合使用将使术中滴定能力大大增强,副作用减少,可能降低术后残余麻痹的发生率并提高患者安全性。