Institute for Social Science Research, The University of Queensland, Indooroopilly, QLD, 4068, Australia.
School of Clinical Medicine, Rural Clinical School, The University of Queensland, Hervey Bay, QLD, 4655, Australia.
Drug Saf. 2018 Nov;41(11):1023-1033. doi: 10.1007/s40264-018-0687-6.
Prescription opioid use has increased rapidly in developed countries, as have fatalities and other related adverse events. This review examines the intrinsic characteristics of opioids, including their mechanisms of action and pharmacokinetic and pharmacodynamic properties, to determine how the use of a regonised pharmacological remedy for a medically confirmed ailment could result in an accidental fatality. Opioids trigger biological processes that inhibit their own therapeutic effect. Prolonged use of opioids can result in activation of pronociceptive systems, leading to opioid-induced hyperalgesia and tolerance, while opioid metabolites can antagonise the antinociceptive action of the parent drug, also leading to opioid-induced hyperalgesia and tolerance. Pain stimulates respiration and counteracts the respiratory depression effect of opioids. Analgesia from opioids leads to loss of this protective mechanism, leading to increased risk of death due to respiratory failure. Increased patient counseling during opioid prescribing and dispensing, and limiting prescription to short-term use in non-malignant pain, may decrease the adverse effects of opioids. The vast majority of patients who unintentionally experience serious adverse events from pharmaceutical opioids do not start out as drug seekers. Even opioid use within prescribing guidelines can place some patients at risk of death and may prevent patients from seeking help for prescription opioid dependence.
处方类阿片在发达国家的使用迅速增加，与之相关的死亡和其他不良事件也随之增加。本综述检查了阿片类药物的内在特征，包括其作用机制、药代动力学和药效学特性，以确定一种公认的用于治疗医学疾病的药理学方法如何导致意外死亡。阿片类药物引发的生物过程会抑制其自身的治疗效果。长期使用阿片类药物会导致促伤害系统的激活，导致阿片类药物引起的痛觉过敏和耐受，而阿片类药物的代谢物可以拮抗母体药物的镇痛作用，也会导致阿片类药物引起的痛觉过敏和耐受。疼痛会刺激呼吸，抵消阿片类药物的呼吸抑制作用。阿片类药物的镇痛作用会导致这种保护机制丧失，从而增加因呼吸衰竭导致死亡的风险。在开具阿片类药物处方和配药时增加患者咨询，并将处方限制在非恶性疼痛的短期使用，可能会减少阿片类药物的不良反应。绝大多数意外发生严重药物不良反应的患者并非一开始就寻求药物。即使按照处方指南使用阿片类药物，也会使一些患者面临死亡风险，并可能使患者无法寻求治疗处方类阿片依赖。
