Masaki Eiji
Department of Anesthesiology, Saitama Medical School, Saitama 350-0451.
Masui. 2006 Jul;55(7):849-55.
Besides its cardioinhibitory effects, short-acting beta1-adrenergic receptor antagonists, landiolol and esmolol are reported to exert antinociceptive and anesthetic sparing effects in animal and human subjects. For example, esmolol reduces the anesthetic requirements for skin incision during propofol/N2O and morphine anesthesia in human and inhibits nociceptive responses following formalin injection in rats. It is also suggested that landiolol decreases BIS response to tracheal intubation during sevoflurane anesthesia. Several possible mechanisms, such as changing pharmacokinetics of opioid and implication with inhibitory G protein, for short-acting beta1-adrenergic receptor antagonists to produce antinociceptive effects were proposed. However, direct mechanism underling antinociceptive effects of short-acting beta1-adrenergic receptor antagonists has not been fully established. The merits to use short-acting beta1-adrenergic receptor antagonists as anesthetic adjuvants could be to reduce anesthetic and opioid requirements (thus, to avoid its side effects such as nausea and vomiting), to maintain hemodynamic stability, and to achieve early recovery from anesthesia. Administration of a sufficient dose of a short-acting beta1-adrenergic receptor antagonist, for example by neuraxial route, may potentially be a new treatment strategy for the perioperative pain, although further study is necessary to establish its efficacy and toxicity. Short-acting beta1-adrenergic receptor antagonists will be used as agents for antinociception in future.
除了具有心脏抑制作用外,据报道,短效β1肾上腺素能受体拮抗剂兰地洛尔和艾司洛尔在动物和人类受试者中具有抗伤害感受和节省麻醉药的作用。例如,艾司洛尔可降低人体在丙泊酚/一氧化二氮和吗啡麻醉期间皮肤切开所需的麻醉剂量,并抑制大鼠福尔马林注射后的伤害性反应。也有研究表明,兰地洛尔可降低七氟醚麻醉期间气管插管时的脑电双频指数(BIS)反应。有人提出了几种可能的机制,如改变阿片类药物的药代动力学以及与抑制性G蛋白的相互作用,来解释短效β1肾上腺素能受体拮抗剂产生抗伤害感受作用的原因。然而,短效β1肾上腺素能受体拮抗剂抗伤害感受作用的直接机制尚未完全明确。使用短效β1肾上腺素能受体拮抗剂作为麻醉辅助药物的优点可能包括减少麻醉药和阿片类药物的用量(从而避免恶心和呕吐等副作用)、维持血流动力学稳定以及实现麻醉后的早期恢复。例如通过神经轴途径给予足够剂量的短效β1肾上腺素能受体拮抗剂,可能是围手术期疼痛的一种新治疗策略,不过还需要进一步研究来确定其疗效和毒性。短效β1肾上腺素能受体拮抗剂未来将用作抗伤害感受药物。