遗传药理学与个体化用药

~~遗传药理学与个体化用药@蔡卫民$上海第二医科大学附属瑞金医院药剂科!上海200025遗传药理学;;个体化用药;;治疗药物监测     

遗传药理学与个体化用药(续)

4　传统TDM与遗传药理学的比较在传统TDM中 ,我们假设血浆药物浓度能反映出药物作用部位的浓度 ,从而使药物浓度可以将药动学 (药物浓度—时间过程 )和药效学 (药物效应—时间关系 )结合起来。从分子水平来考虑 ,药动学是由药物代谢酶所决定 ,而药效学则置于药物目标蛋白的控制之下。因此 ,将遗传药理学应用于个体化用药 ,我们就可以比传统TDM更向前跨进一步。通过基因型测定 ,我们就可以评价药物代谢酶、转运体、目标或受体蛋白的遗传多态性 ,群体中存在的许多药物效应和不良反应方面的个体差异都应归因于遗传多态性。下面将传统TDM与…     

遗传药理学与抗肿瘤药物个体化用药(下)

2抗肿瘤药物遗传药理学研究进展2.1他莫昔芬他莫西芬(tamoxifen,TAM),是一种非固醇类抗雌激素药物,目前广泛用于雌激素受体(ER)阳性的乳腺癌患者的预防和治疗。TAM结构与雌激素相似,存在Z型和E型两个异构体。两者物理化学性质各异,生理活性也不同,E型具有弱雌激素活性,Z型则具有抗雌激素作用。如果乳癌细     

遗传药理学与抗肿瘤药物个体化用药(上)

众所周知,不同人群服用同一剂量药物在药效和毒性反应上可能出现较大差异,因而在少数病人中会出现不可预测并危及生命或致死的不良反应。这种个体化差异不能完全被肝肾功能、年龄、生活方式或合并用药及病人依从性等因素来很好地解释,此时遗传因素或许是药物疗效和毒性的重要决定因素。遗传药理学研究目的就是将这些遗传因素鉴别清楚,根据个体基因变异与药效差异的关系设计临床个体化用药方案,以保证临床用药的安全、有效和经济。     

药物基因组学与个体化用药

药物基因组学是研究基因多态性与药物作用的多样性之间的关系的一门新兴学科,药物基因组学可以改善病人用药,提高用药的安全性和有效性,减少药物不良反应的发生,为个体化用药提供理论依据。本文介绍了药物基因组学的概念、研究内容和方法及其在临床个体化用药中的应用及意义。     

静脉用药调配中心在临床安全合理用药中的作用

目的探讨我院静脉用药调配中心在临床安全合理用药中的作用。方法回顾性分析我院静脉用药调配中心的临床用药情况。结果2012年我院静脉用药调配中心共审核不合理用药医嘱566条,其中经医师更正的医嘱554条,更正率达97．88％。结论我院静脉用药调配中心工作的开展,加强了医生、药师、护士之间的联系和沟通,提高了成品输液质量、药品管理水平和人员职业防护,在促进临床合理用药以及保障用药安全方面发挥着重要的作用。     

临床药理学讲座 药效学与临床用药

药理学由药效动力学和药代动力学组成,主要研究药物与机体之间的相互作用。本文重点从药效动力学的角度阐述它与临床用药的关系。1 与药效学有关的基本理论1.1 何谓药效动力学 药效动力学(简称药效学)主要研究药物是如何影响人体的,即药物在人体产生的生理、生化效应及其机制。在理论上,它是药理学的理论基础;在实践上它可指导合理用药,发挥药物的最佳疗效,防止药物的不良反应。1.2 药物作用及作用机理     

时辰药理学与临床合理用药

时辰药理学又称时间药理学,是研究药物与生物周期性相互关系的一门边缘学科。依据时辰药理学确定口服药物最佳给药方法,对减少不良反应、最大程度发挥药效具有特殊意义而在实际的临床工作中,传统处方中的医嘱只是简单的服药频次,对于具体何时服药门诊医师也并没有更多的解释,以致患者只能依照药品说明书服药。为此,笔者在查阅参考文献的同时依据时辰药理学对我院门诊常用药品服用时间、服用方法等进行了汇总,以供临床参考。     

时辰药理学与临床合理用药

目的：论述人体生物节律和时辰药理学的关系，结合临床合理用药。方法：参考有关文献和资料，结合临床实际。进行汇总，分析并加以阐述。结果：同一种药物，同一剂量，在1d中的不同时间服用，其疗效和毒性可能相差几倍，甚至几十倍。结论：临床用药若能依据人体的生物节律和药物作用的时辰节律来选择最佳用药时间，确定给药方案，既可提高疗效。还可减少药物用量，并最大限度地减少不良反应的产生。     

Pharmacogenetics and rational drug use around the world

The WHO embraces evidence-based medicine to formulate an essential medicines list (EML) considering disease prevalence, drug efficacy, drug safety and cost-effectiveness. The EML is used by developing countries to build a national formulary. As pharmacogenetics in developed countries evolves, the Pharmacogenetics for Every Nation Initiative (PGENI) convened with representatives from China, Mexico, Ghana and South Africa in August 2009 to evaluate the use of human pharmacogenetics to enhance global drug use policy. The diseases causing mortality, the lack of integration of pharmacovigilance at the national formulary level, the pharmacogenetics research agenda and pharmacogenetics clinician education did not differ greatly among the countries. While there are many unanswered questions, systematically incorporating pharmacogenetics at the national formulary level promises to improve global drug use.     

药物基因组学与安全用药

由于人类基因组计划的实施,特别是目前较为精确的人类基因组全序列的初步绘制,以及大量单核苷酸多态性 (single-nucleotide polymorphisms,SNPs)的检测与发现,以基因水平研究药物反应个体差异的药物基因组学在生物技术和医药工业界掀起了前所未有的热潮.     

N-acetyltransferases: Pharmacogenetics and clinical consequences of polymorphic drug metabolism

Since the discovery of polymorphicN-acetylation of drugs nearly 40 years ago, great progress has been made in understanding the molecular genetics of acetylation as well as the clinical consequences of being a rapid or slow acetylator. Inborn errors (several different alleles) at the NAT2 locus are responsible for the traditional acetylator polymorphism. Studies have revealed variant alleles at the NAT1 locus as well. The consequences of pharmacogenetic variation in these enzymes include (i) altered kinetics of specific drug substrates; (ii) drug-drug interactions resulting from altered kinetics; (iii) idiosyncratic adverse drug reactions. The latter have been extensively investigated for the arylamine-containing sulfonamide antimicrobial drugs. Individual differences in multiple metabolic pathways can increase the likelihood of covalent binding of reactive metabolites of the drugs to cell macromolecules with resultant cytotoxicity and immune response to neoantigens. This can result clinically in an idiosyncratic hypersensitivity reaction, manifested by fever, skin rash, and variable toxicity to organs including liver, bone marrow, kidney, lung, heart, and thyroid. Slow acetylation by NAT2 is a risk factor for such reactions to sulfonamides. Given the incidence of these severe adverse drug reactions (much less than 1/1000), slow acetylation cannot be the sole mechanism of predisposition in the population. Differences in rates of production of hydroxylamine metabolites of the drugs by cytochrome P450 (CYP2C9), myeloperoxidase, and thyroid, roxidase, along with an inherited abnormality in detoxification of the hydroxylamines are critically important in determining individual differences in adverse reaction risk. Both NATs, particularly NAT1, also can further metabolize hydroxylamine metabolites toN-acetoxy derivatives. Intensive investigation of patients with these rare adverse reactions using a variety of tools fromin vitro cell toxicity assays through molecular genetic analysis will help elucidate mechanisms of predisposition and ultimately lead to diagnostic tools to characterize individual risk and prevent idiosyncratic drug toxicity.     

Pharmacogenetics of drug metabolism

Genetic variation in drug metabolizing capacity deserves attention not only in terms of inter-individual but also in terms of inter-ethnic differences.     

Pharmacogenetics: improving drug and dose selection

Considerable interindividual variability exists in patient responses to drug therapy. Differences in DNA sequence can affect the disposition, efficacy, and safety of a drug. Knowledge of pharmacogenetics may be applied toward understanding and managing such interindividual variability. Increasingly, pharmacogenetic language is being added to drug labels, and genotyping is performed either to select the drug or adjust the dose to an individual. In this article we discuss the current uses of genotyping for managing drug therapy, and issues related to the clinical uptake of pharmacogenetics.     

时辰药理学与合理用药

参考有关文献和资料，结合，临床用药，论述时辰药理学与人体生物节律的关系，为临床选择最佳用药时间提供参考。     

静脉药物集中配制及其在安全用药中的意义

本文介绍了静脉药物配置中心(PIVA)药学服务工作的实践与体会,为静脉药物集中配制工作的开展提供借鉴与参考。在PIVA里,药师将充分发挥药学专业知识专长,通过审核处方,可有效地提高合理用药水平,减少用药失误;PIVA高洁净度的配置环境及规范化的配制操作过程,保证了药液的无菌性、稳定性、相容性和输液质量;药品实行集中管理,有利于减少药品流失、降低分剂量成本。PIVA的启用拓展了药学服务内涵,使其职能由传统调配型向″以病人为中心″的药学服务模式转变。