Pain Clinic, Helsinki University Central Hospital, Finland.
Curr Pharm Des. 2012;18(37):6079-89. doi: 10.2174/138161212803582423.
Opioids are increasingly used to manage not only acute but also chronic pain and heroine addiction. These patients usually receive many other medications that can interfere with the effects of opioids and vice versa. Patients often need combinations of drugs for their pain management, for treating opioid-related adverse effects or for other indications including depression and anxiety. Several antibiotics can also have interactions with opioids. It is important to understand what potential interactions exist between opioids and other drugs. Drug interactions can occur due to pharmacokinetic interactions including effects of absorption, metabolic pathways, drug transport through membranes and protein binding. Our knowledge of the metabolism of opioids has significantly increased over the last years and it is now possible to appreciate the role CYP enzymes, mainly CYP 2D6 and 3A4/5, in the metabolism of many commonly used opioids like codeine and oxycodone. Our knowledge regarding the role of the transporter proteins in drug interactions related to opioids is unfortunately meagre. Opioids inhibit the gastrointestinal system and can thus change the absorption of other drugs. Opioids can have synergistic or additive interactions with other drugs that have analgesic or sedative effects. Endogenous opioids control many physiological functions and exogenous opioids can have effects on all important transmitter systems (cholinergic, GABAergic, dopaminergic and serotonergic). The literature in this field is mainly based on case reports. Interindividual differences play an important role. Other potential interactions include prolongation of the QT-interval and lowering of the threshold for convulsions.
阿片类药物不仅越来越多地用于治疗急性疼痛，也越来越多地用于治疗慢性疼痛和海洛因成瘾。这些患者通常还会接受许多其他药物治疗，这些药物可能会干扰阿片类药物的作用，反之亦然。患者通常需要组合使用药物来治疗疼痛、治疗与阿片类药物相关的不良反应或治疗其他疾病，包括抑郁和焦虑。一些抗生素也可能与阿片类药物发生相互作用。了解阿片类药物与其他药物之间可能存在哪些潜在相互作用非常重要。药物相互作用可能是由于药代动力学相互作用引起的，包括吸收、代谢途径、药物通过细胞膜的转运和蛋白结合的影响。近年来，我们对阿片类药物代谢的了解显著增加，现在可以了解细胞色素 P450 酶（主要是 CYP2D6 和 3A4/5）在许多常用阿片类药物（如可待因和羟考酮）代谢中的作用。遗憾的是，我们对与阿片类药物相关的药物相互作用中转运蛋白作用的了解还很有限。阿片类药物抑制胃肠道系统，因此可以改变其他药物的吸收。阿片类药物与具有镇痛或镇静作用的其他药物可能具有协同或相加相互作用。内源性阿片类物质控制着许多生理功能，外源性阿片类物质可以对所有重要的递质系统（胆碱能、γ-氨基丁酸能、多巴胺能和 5-羟色胺能）产生影响。该领域的文献主要基于病例报告。个体间差异起着重要作用。其他潜在的相互作用包括 QT 间期延长和惊厥阈值降低。
