阿片类药物是急性疼痛管理的支柱,并产生其作用和副作用(例如,容忍度,阿片类药物使用障碍和免疫抑制)通过与阿片受体相互作用。我将在麻醉相关性的一些有争议的领域中讨论阿片类药物药理学。主要的阿片类药物目标是µ(mu,MOP)受体,但阿片受体家族的其他成员,δ(delta;DOP)和κ(kappa;KOP)阿片受体也产生镇痛作用。这些对纳洛酮敏感。有重要的临床发展与Nociceptin/OrphaninFQ(NOP)受体有关,一种对纳洛酮不敏感的阿片受体。更好地了解阿片类药物作用和副作用的驱动因素可能有助于分离副作用和生产更安全的药物。阿片类药物与受体正构位点结合以产生其作用,并且可以与单体或同源,异二聚体受体。一些配体可以驱动一个细胞内途径而不是另一个。这是偏向激动(或功能选择性)的基础。可以变构地调节正位位点处的阿片样物质作用,并且正在开发增强阿片样物质作用的正变构调节剂。以及靶向配体-受体相互作用和转导,调节受体表达和因此功能也是可处理的。有证据表明,表观遗传与不同类型的疼痛以及药物滥用有关。只要阿片类药物的叙述是由“阿片类药物危机”定义的,消除它们的动力就可以加快步伐。这将拒绝在有效的地方使用,以及在低收入国家使用吗啡来缓解疼痛。
Opioids are a mainstay in acute pain management and produce their effects and side effects (e.g., tolerance, opioid-use disorder and immune suppression) by interaction with opioid receptors. I will discuss opioid pharmacology in some controversial areas of enquiry of anaesthetic relevance. The main opioid target is the µ (mu,MOP) receptor but other members of the opioid receptor family, δ (delta; DOP) and κ (kappa; KOP) opioid receptors also produce analgesic actions. These are naloxone-sensitive. There is important clinical development relating to the Nociceptin/Orphanin FQ (NOP) receptor, an opioid receptor that is not naloxone-sensitive. Better understanding of the drivers for opioid effects and side effects may facilitate separation of side effects and production of safer drugs. Opioids bind to the receptor orthosteric site to produce their effects and can engage monomer or homo-, heterodimer receptors. Some ligands can drive one intracellular pathway over another. This is the basis of biased agonism (or functional selectivity). Opioid actions at the orthosteric site can be modulated allosterically and positive allosteric modulators that enhance opioid action are in development. As well as targeting ligand-receptor interaction and transduction, modulating receptor expression and hence function is also tractable. There is evidence for epigenetic associations with different types of pain and also substance misuse. As long as the opioid narrative is defined by the \'opioid crisis\' the drive to remove them could gather pace. This will deny use where they are effective, and access to morphine for pain relief in low income countries.