吗啡镇痛个体差异的遗传药理学进展
作者:
作者单位:

作者简介:

通讯作者:

中图分类号:

基金项目:

中国医学科学院中央级公益性科研院所基本科研业务费(2016ZX310044)。


Genetic pharmacology of individual differences in morphine analgesia
Author:
Affiliation:

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    吗啡是广泛使用的一种阿片类镇痛药,不同个体间对吗啡镇痛的敏感性有较大差异,长期使用吗啡会导致镇痛效果降低而产生耐受,耐受的易感性在个体间也有较大差异,这些都给吗啡在临床的优化应用带来很多困扰。遗传因素通过控制蛋白质编码从药代动力学和药效动力学两方面影响个体对吗啡镇痛的反应。P-糖蛋白编码基因ABCB1的多样性影响吗啡的转运和分布,编码UDP-葡糖醛酸转移酶的基因UGT2B7的多样性则控制吗啡代谢转化。吗啡的主要作用靶点μ阿片受体的编码基因OPRM1和儿茶酚-O-甲基转移酶的编码基因COMT的多样性引起的下游信号通路反应性差异影响吗啡镇痛药效学。未来对吗啡镇痛个体差异的遗传学研究需要使用遗传多样性更复杂的个体,采用更系统全面的分析方法从更广的范围筛选关键基因。阐明遗传多样性与个体间对吗啡镇痛反应差异的关系,将有助于理解吗啡镇痛的遗传药理学调控机制,为临床吗啡镇痛使用实现个人化、精确化甚至联合基因治疗改善吗啡镇痛提供依据。

    Abstract:

    Morphine is a widely used opioid analgesic, but great individual differences in response to morphine such as sensitivity to analgesia and susceptibility to tolerance, which due to chronic morphine treatment, are great challenges for clinicians to optimize treatment strategy. Genetic factors play an important role in individual variability to morphine treatment. Individual responses to morphine are influenced by various gene-encoded-proteins implied in pharmacokinetics and pharmacodynamics. Variants of P-glycoprotein encoding gene ABCB1 regulate transportation and distribution of morphine and affect analgesic effect. Diversity in UDP-glucuronosyl transferase encoding gene UGT2B7, whose encoding product catalyzing morphine to glycosylated metabolites contribute to different response to morphine in a pharmacokinetic way. Nevertheless, variants in μ-opioid receptor encoding gene OPRM1 and catechol-O-methyltransferase encoding gene COMT regulate morphine-induced downstream signaling and influence morphine analgesia in a pharmacodynamic way. It is necessary to employ individuals with more complex genetic diversity and screen in a larger scope through a more comprehensive system to find the key genes involved in individual differences of morphine analgesia in future research. Elucidating the association between genetic variability and individual differences will help to figure out the mechanism of pharmacogenetic regulation in morphine analgesia. It will provide basis for personalized and accurate utility of morphine or even combining with gene therapy to improve the analgesic effect.

    参考文献
    相似文献
    引证文献
引用本文

杨银,孟爱民.吗啡镇痛个体差异的遗传药理学进展[J].中国比较医学杂志,2017,27(10):107~112.

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2017-02-13
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期: 2017-10-23
  • 出版日期:
自2024年1期开始,杂志参考文献改为中英文对照,具体格式要求可置下载中心查看!
关闭