Department of Anaesthesiology & Intensive Care Medicine, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Pharmacogenomics. 2010 Jun;11(6):843-64. doi: 10.2217/pgs.10.47.
Genomic variations influencing response to pharmacotherapy of pain are currently under investigation. Drug-metabolizing enzymes represent a major target of ongoing research in order to identify associations between an individual's drug response and genetic profile. Polymorphisms of the cytochrome P450 enzymes (CYP2D6) influence metabolism of codeine, tramadol, hydrocodone, oxycodone and tricyclic antidepressants. Blood concentrations of some NSAIDs depend on CYP2C9 and/or CYP2C8 activity. Genomic variants of these genes associate well with NSAIDs' side effect profile. Other candidate genes, such as those encoding (opioid) receptors, transporters and other molecules important for pharmacotherapy in pain management, are discussed; however, study results are often equivocal. Besides genetic variants, further variables, for example, age, disease, comorbidity, concomitant medication, organ function as well as patients' compliance, may have an impact on pharmacotherapy and need to be addressed when pain therapists prescribe medication. Although pharmacogenetics as a diagnostic tool has the potential to improve patient therapy, well-designed studies are needed to demonstrate superiority to conventional dosing regimes.
目前正在研究影响疼痛药物治疗反应的基因组变异。药物代谢酶是正在进行的研究的主要目标，目的是确定个体的药物反应与遗传特征之间的关联。细胞色素 P450 酶（CYP2D6）的多态性影响可待因、曲马多、氢可酮、羟考酮和三环类抗抑郁药的代谢。一些 NSAIDs 的血药浓度取决于 CYP2C9 和/或 CYP2C8 活性。这些基因的基因组变异与 NSAIDs 的副作用特征密切相关。其他候选基因，如编码（阿片类）受体、转运体和其他对疼痛管理中药物治疗重要的分子，也在讨论中；然而，研究结果往往存在争议。除了遗传变异，其他变量，例如年龄、疾病、合并症、伴随用药、器官功能以及患者的依从性，可能会对药物治疗产生影响，在疼痛治疗师开处方时需要加以考虑。尽管药物遗传学作为一种诊断工具具有改善患者治疗的潜力，但需要进行精心设计的研究来证明其优于传统的剂量方案。
