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药物遗传学分析与个体化治疗在退行性脊柱疾病中的应用。

Pharmacogenetic profiling and individualised therapy in the treatment of degenerative spinal conditions.

机构信息

National Spinal Injuries Unit, Mater Misericordiae University Hospital, Eccles St., Dublin, D07 R2WY, Ireland.

School of Medicine, Trinity College, Dublin, Ireland.

出版信息

Ir J Med Sci. 2023 Jun;192(3):1215-1224. doi: 10.1007/s11845-022-03112-9. Epub 2022 Aug 13.

Abstract

Patients presenting with degenerative spinal changes are often poor surgical candidates due to associated co-morbidities, frailty, or sarcopenia. Additionally, surgeries of a degenerative spine can prove difficult due to the distortion of normal surgical anatomy. Therefore, many patients are managed conservatively with a variety of modalities, including over-the-counter and prescription medications. Nevertheless, several patients do not experience adequate relief from pain with analgesic medications, precipitating multiple hospital visits, and usage of resources. As a result, back pain is regarded as a major economic burden, with total costs of associated treatment exceeding $100 billion annually. Pharmacogenetics is a relatively novel method of evaluating an individual's response to analgesic medications, through analysis of germline polymorphisms. It entails obtaining a genetic sample, often via buccal swab or peripheral blood sample, and genetic analysis achieved through either polymerase chain reaction +/- Sanger sequencing, microassays, restriction length fragment polymorphism analysis, or genetic library preparation and next generation sequencing. The potential efficacy of pharmacogenetic analysis has been highlighted across several specialities to date. However, a paucity of evidence exists regarding spine surgery populations. Nevertheless, regular prospective pharmacogenetic analysis may ultimately prove beneficial when concerning degenerative spinal cohorts due to aforementioned surgical and economic considerations. The purpose of this narrative review is to outline how metaboliser profile variants affect the pharmacokinetics of specific analgesia used to treat back pain, and to discuss the current potential and limitations of employing regular pharmacogenetic analysis for spine surgery populations with degenerative conditions.

摘要

患有退行性脊柱变化的患者常因合并症、虚弱或肌肉减少症而成为较差的手术候选者。此外,由于正常手术解剖结构的扭曲,退行性脊柱手术可能会变得困难。因此,许多患者通过各种方式进行保守治疗,包括非处方和处方药物。然而,一些患者使用镇痛药物后无法充分缓解疼痛,导致多次就诊和资源使用。因此,背痛被认为是一个主要的经济负担,相关治疗的总费用每年超过 1000 亿美元。药物遗传学是一种通过分析种系多态性来评估个体对镇痛药物反应的相对较新的方法。它需要获取遗传样本,通常通过颊拭子或外周血样,并通过聚合酶链反应 +/- Sanger 测序、微阵列、限制性片段长度多态性分析、或遗传文库制备和下一代测序来进行基因分析。迄今为止,药物遗传学分析的潜在疗效已在多个专业领域得到强调。然而,关于脊柱手术人群的证据仍然很少。然而,由于上述手术和经济方面的考虑,定期进行前瞻性药物遗传学分析最终可能对退行性脊柱患者群体有益。本叙述性综述的目的是概述代谢物基因型变异如何影响用于治疗背痛的特定镇痛药物的药代动力学,并讨论在患有退行性疾病的脊柱手术人群中常规进行药物遗传学分析的当前潜在作用和局限性。

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