Averting Opioid-induced Respiratory Depression without Affecting Analgesia
Averting Opioid-induced Respiratory Depression without Affecting Analgesia
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DOI：
10.1097/aln.0000000000002184
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发表时间：
2018-05-01
期刊：
影响因子：
8.8
通讯作者：
Niesters, Marieke
中科院分区：
文献类型：
--
作者：
Dahan, Albert;van der Schrier, Rutger;Niesters, Marieke
中枢控制系统对外源性阿片类镇痛药非常敏感。特别是呼吸抑制是一种潜在的致命并发症，当阿片类药物过量或与其他抑制剂（如睡眠药物或酒精）联合使用时可能会发生。死亡发生在接受阿片类药物治疗的急性和慢性疼痛患者以及滥用处方或非法阿片类药物以获得享乐的个人中。减轻阿片类药物诱导的呼吸抑制的一个重要策略是与非阿片类呼吸兴奋剂联合治疗。有效的兴奋剂可防止呼吸抑制，而不影响阿片类镇痛反应。目前正在研究几种非阿片类呼吸兴奋剂。大多数作用于脑干呼吸网络内的位点，包括作用于α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（ampakine）、5-羟色胺受体激动剂、磷酸二酯酶-4抑制剂、D-1-多巴胺受体激动剂、内源性肽甘氨酰-谷氨酰胺和促甲状腺素释放激素的药物。其它的在外周作用于在颈动脉体的氧敏感细胞上表达的钾通道，例如多沙普仑和GAL 021（Galleon Pharmaceuticals Corp.，美国）。在这篇综述中，我们批判性地评价这些药物的疗效。我们的结论是，没有一个实验药物是足够的阿片类药物诱导的呼吸抑制的治疗用途，所有需要进一步研究的疗效和毒性。然而，所有讨论的药物都强调了潜在的作用机制和进一步研究和开发的可能模板。
The ventilatory control system is highly vulnerable to exogenous administered opioid analgesics. Particularly respiratory depression is a potentially lethal complication that may occur when opioids are overdosed or consumed in combination with other depressants such as sleep medication or alcohol. Fatalities occur in acute and chronic pain patients on opioid therapy and individuals that abuse prescription or illicit opioids for their hedonistic pleasure. One important strategy to mitigate opioid-induced respiratory depression is cotreatment with nonopioid respiratory stimulants. Effective stimulants prevent respiratory depression without affecting the analgesic opioid response. Several pharmaceutical classes of nonopioid respiratory stimulants are currently under investigation. The majority acts at sites within the brainstem respiratory network including drugs that act at alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (ampakines), 5-hydroxytryptamine receptor agonists, phospodiesterase-4 inhibitors, D-1-dopamine receptor agonists, the endogenous peptide glycyl-glutamine, and thyrotropin-releasing hormone. Others act peripherally at potassium channels expressed on oxygen-sensing cells of the carotid bodies, such as doxapram and GAL021 (Galleon Pharmaceuticals Corp., USA). In this review we critically appraise the efficacy of these agents. We conclude that none of the experimental drugs are adequate for therapeutic use in opioid-induced respiratory depression and all need further study of efficacy and toxicity. All discussed drugs, however, do highlight potential mechanisms of action and possible templates for further study and development.