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药物遗传学:是一种分子层面的复杂技术,还是心脏病专家的新型临床工具?

Pharmacogenetics: a molecular sophistication or a new clinical tool for cardiologists?

作者信息

Dirckx C, Donati M B, Iacoviello L

机构信息

Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, S. Maria Imbaro, CH, Italy.

出版信息

Ital Heart J. 2000 Oct;1(10):662-6.

Abstract

The study of genetic risk factors for multifactorial diseases is attracting increasing interest. In particular interest has been focused on the interaction between genetic polymorphisms and environmental factors in determining the risk of disease. Among environmental factors therapeutic approaches should be considered. Therapeutic responses to a given drug, failure of drug efficacy, interindividual variability in side effects and toxicity of drugs could be at least partially accounted for by genetic polymorphisms. This paper summarizes the presently available applications of genetic concepts to some drugs commonly used in patients with cardiovascular disease. Statins and probucol fail to lower cholesterol levels in carriers of specific polymorphisms. The progression of cardiovascular disease is decreased by pravastatin only when certain polymorphisms are present. Induction problems and bleeding complications of warfarin occur in subgroups of populations carrying specific genetic variants of key enzymes in the drug metabolism. A new interpretation of the results of a thrombosis prevention trial will be given in the light of a genetic approach to pharmacology; indeed, prevention and treatment of thrombotic disease could be better focused on the basis of this knowledge. Future clinical trials and cost-effectiveness evaluation of drugs should be conducted taking these gene-drug interactions into account.

摘要

对多因素疾病遗传风险因素的研究正吸引着越来越多的关注。特别令人感兴趣的是基因多态性与环境因素在决定疾病风险方面的相互作用。在环境因素中,应考虑治疗方法。对特定药物的治疗反应、药物疗效不佳、个体间药物副作用和毒性的变异性至少部分可由基因多态性来解释。本文总结了目前遗传概念在心血管疾病患者常用的一些药物中的应用。他汀类药物和普罗布考在特定多态性携带者中无法降低胆固醇水平。仅当存在某些多态性时,普伐他汀才能减缓心血管疾病的进展。华法林的诱导问题和出血并发症发生在携带药物代谢关键酶特定基因变体的人群亚组中。将根据药理学的遗传方法对一项血栓形成预防试验的结果给出新的解释;事实上,基于这些知识,血栓性疾病的预防和治疗可以更有针对性。未来的临床试验以及药物的成本效益评估应考虑这些基因 - 药物相互作用。

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