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药物诱导的皮肤不良反应:药物基因组学在其预防中的作用。

Drug-Induced Skin Adverse Reactions: The Role of Pharmacogenomics in Their Prevention.

机构信息

Department of Pharmacology, Faculty of Medicine, University of Thessaly, Biopolis, 41500, Larissa, Greece.

Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, Biopolis, 41500, Larissa, Greece.

出版信息

Mol Diagn Ther. 2018 Jun;22(3):297-314. doi: 10.1007/s40291-018-0330-3.

Abstract

Adverse drug reactions (ADRs) affect many patients and remain a major public health problem, as they are a common cause of morbidity and mortality. It is estimated that ADRs are responsible for about 6% of hospital admissions and about 9% of hospitalization costs. Skin is the organ that is most frequently involved in ADRs. Drug-induced skin injuries vary from mild maculopapular eruptions (MPE) to severe cutaneous adverse reactions (SCARs) that are potentially life threatening. Genetic factors have been suggested to contribute to these SCARs, and most significant genetic associations have been identified in the major histocompatibility complex (MHC) genes. Common drugs associated with SCARs connected with strong genetic risk factors include antiepileptic drugs (AEDs), allopurinol, abacavir, nevirapine, sulfonamides, dapsone, non-steroidal anti-inflammatory drugs (NSAIDs), and analgesic drugs. However, genetic associations vary between different ethnic populations. Differences may in part be explained by the different prevalence of HLA (human leukocyte antigen) alleles among ethnic groups. In this review, we present and discuss the recent advances in genetic associations with ADRs in the skin. Many of these ADRs are now preventable with pharmacogenetic screening.

摘要

药物不良反应(ADRs)影响许多患者,仍然是一个主要的公共卫生问题,因为它们是发病率和死亡率的一个常见原因。据估计,ADRs 约占住院人数的 6%,约占住院费用的 9%。皮肤是最常涉及 ADR 的器官。药物引起的皮肤损伤从轻度斑丘疹(MPE)到严重的皮肤不良反应(SCARs)不等,后者可能危及生命。遗传因素被认为是这些 SCARs 的原因,并且在主要组织相容性复合体(MHC)基因中已经确定了大多数重要的遗传关联。与 SCARs 相关的具有强烈遗传风险因素的常见药物包括抗癫痫药物(AEDs)、别嘌醇、阿巴卡韦、奈韦拉平、磺胺类药物、氨苯砜、非甾体抗炎药(NSAIDs)和镇痛药。然而,遗传关联在不同的种族群体之间存在差异。这种差异部分可以用不同种族群体中 HLA(人类白细胞抗原)等位基因的不同流行率来解释。在这篇综述中,我们介绍并讨论了与皮肤 ADRs 相关的遗传关联的最新进展。其中许多 ADRs 现在可以通过药物遗传学筛查来预防。

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