药物基因组学在预防药物不良反应中的应用

药物不良反应是，隘床药物治疗的一个难题，目前已成为危害人类健康的重要公共卫生问题，如何合理用药避免药物不良反应具有重要意义。随着人类基因组计划的完成和药物遗传靶标的不断发现，药物基因组学已成为研究药物不良反应的一个全新领域，本文主要阐述遗传因素与药物不良反应的关系     

老年患者多重用药合理方案的制定

全球老龄化时代已到来,老年人健康问题已成为全球焦点。老年人常患有多种疾病,多重用药不可避免。多项研究显示,老年患者用药存在许多潜在不恰当的现象,加之药物本身存在的不良反应及药物之间的相互作用产生的不良反应,给老年患者造成严重伤害。因此,发现、筛查不恰当用药的方法,制定合理用药方案,减少老年人由于多重用药导致的不良反应的发生就显得尤为重要。     

浅谈药物不良反应的影响因素及对策

目的探讨影响药物不良反应(ADR)的因素,为临床合理用药提供科学依据。方法依据文献分析我院近年用药情况,查找影响药物不良反应的因素。结果个体差异、性别、年龄、遗传、给药方法及给药途径、用药时间、给药剂量、浓度等是影响药物不良反应的主要因素。结论掌握影响药物不良反应的主要因素是避免药物不良反应发生的前提。     

遗传药理学在临床安全用药中的作用

本文介绍了个体遗传多态性以及遗传药理学在安全用药中的作用。加深对药理效应和药物代谢个体差异的遗传因素及个体化用药的了解,从而提高临床疗效,减少药物不良反应。     

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。     

药物不良反应的遗传学基础

药物治疗的疗效、剂量和毒性反应的个体和种族差异是临床实践和药物开发研究中的一个主要问题.在众多的影响因素中,遗传因素具有很重要的作用.本文主要从药动学和药效学两方面论述遗传因素对药物疗效和不良反应的影响,并综述了个体化用药存在的问题及前景.     

抗菌药物的不良反应及临床处理方法

抗菌药物的不良反应已成为当代医疗中不可忽视的问题,常见的抗菌药物不良反应主要有毒性反应、变态反应、特异性反应及附加损害,抗菌药物不良反应的影响因素较多,临床中应严格按照抗菌药物临床使用的规范要求,合理选择药物、确定用药途径,尽可能地避免联合用药,谨慎选择新药,以提高抗菌药物用药合理性。     

人类白细胞抗原基因多态性与药物不良反应研究进展

药物不良反应已成为危害人类健康的重要公共卫生问题.人类白细胞抗原基因(HLA)是目前已知的人类最复杂基因系统.近年来研究发现,人类白细胞抗原基因多态性与药物不良反应之间有着很强的遗传相关性,且部分研究成果在临床已得到很好地应用.本文就人类白细胞抗原基因多态性与药物不良反应之间的研究及其临床应用进行阐述.     

药物代谢中的药酶特性与临床研究近况

目的:为了促进药物代谢酶在临床上的深入研究。方法:以近几年国内外大量有代表性的论文为依据进行分析、归纳、整理。结果:药物代谢酶大多具有遗传多态性,其活性受相关药物影响,遗传多态性和药物之间代谢性相互作用是临床药物反应千变万化的重要因素。结论:药物代谢酶的认识和研究有助于临床合理用药和减少药物不良反应。     

开展全过程药学服务促进药物合理应用

目前,药物不良反应已成为医疗事故的重要原因[1],而通过开展全过程药学服务,可以显著提高临床合理用药水平,从而减少药物不良反应与临床用药有关事件的发生。     

Genetics or environment in drug transport: the case of organic anion transporting polypeptides and adverse drug reactions

INTRODUCTION: Organic anion transporting polypeptide (OATP) uptake transporters are important for the disposition of many drugs and perturbed OATP activity can contribute to adverse drug reactions (ADRs). It is well documented that both genetic and environmental factors can alter OATP expression and activity. Genetic factors include single nucleotide polymorphisms (SNPs) that change OATP activity and epigenetic regulation that modify OATP expression levels. SNPs in OATPs contribute to ADRs. Environmental factors include the pharmacological context of drug-drug interactions and the physiological context of liver diseases. Liver diseases such as non-alcoholic fatty liver disease, cholestasis and hepatocellular carcinoma change the expression of multiple OATP isoforms. The role of liver diseases in the occurrence of ADRs is unknown. AREAS COVERED: This article covers the roles OATPs play in ADRs when considered in the context of genetic or environmental factors. The reader will gain a greater appreciation for the current evidence regarding the salience and importance of each factor in OATP-mediated ADRs. EXPERT OPINION: A SNP in a single OATP transporter can cause changes in drug pharmacokinetics and contribute to ADRs but, because of overlap in substrate specificities, there is potential for compensatory transport by other OATP isoforms. By contrast, the expression of multiple OATP isoforms is decreased in liver diseases, reducing compensatory transport and thereby increasing the probability of ADRs. To date, most research has focused on the genetic factors in OATP-mediated ADRs while the impact of environmental factors has largely been ignored.     

98例药物不良反应报告分析

目的 探讨药品不良反应（ADRs）发生相关因素以及ADRs对病人身体造成的损害.方法 收集本院2009年1月至2010年12月药物不良反应报告98例进行总结分析.结果 静脉给药途经发生的ADRs有95例,占总例数的96.9%.其中抗菌药物的ADRs发生率最高,有44例,占44.90%.ADRs的临床表现以皮肤及附件系统损害最为常见.联合用药引起的ADRs 10例,占10.20%.结论尽可能减少 ADRs发生相关因素、合理用药,可以减少或避免ADRs的发生,保证病人安全.     

Factors affecting the development of adverse drug reactions (Review article)

Objectives

To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs).

Data Sources

A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards.

Summary

Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen.

Conclusion

Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection.     

加强国家基本药物不良反应监测工作

我国从2009年开始实行基本药物制度,有利于解决用药贵、用药难等现实问题。但是基本药物普及性的提高更加突出了药物不良反应（ADR）监测的重要性,为保障用药安全,药品上市后的安全性再评价十分重要。为了加强国家基本药物ADR的监测工作,阐述我国基本药物ADR监测的现状及存在问题,并提出完善法律体系、明晰基本药物的遴选标准、提高各主体ADR认识的实施建议,为合理用药、保障公众健康提供指导。     

Pharmacogenomics of cardiovascular drugs and adverse effects in pediatrics

Individual response to medication is highly variable. For many drugs, a substantial proportion of patients show suboptimal response at standard doses, whereas others experience adverse drug reactions (ADRs). Pharmacogenomics aims to identify genetic factors underlying this variability in drug response, providing solutions to improve drug efficacy and safety. We review recent advances in pharmacogenomics of cardiovascular drugs and cardiovascular ADRs, including warfarin, clopidogrel, β-blockers, renin-angiotensin-aldosterone system inhibitors, drug-induced long QT syndrome, and anthracycline-induced cardiotoxicity. We particularly focus on the applicability of pharmacogenomic findings to pediatric patients in whom developmental changes in body size and organ function may affect drug pharmacokinetics and pharmacodynamics. Solid evidence supports the importance of gene variants in CYP2C9 and VKORC1 for warfarin dosing and in CYP2C19 for clopidogrel response in adult patients. For the other cardiovascular drugs or cardiovascular ADRs, further studies are needed to replicate or clarify genetic associations before considering uptake of pharmacogenetic testing in clinical practice. With the exception of warfarin and anthracycline-induced cardiotoxicity, there is lack of pharmacogenomic studies on cardiovascular drug response or ADRs aimed specifically at children or adolescents. The first pediatric warfarin pharmacogenomic study indeed indicates differences from adults, pointing out the importance and need for pediatric-focused pharmacogenomic studies.     

EUDRAGENE: European collaboration to establish a case-control DNA collection for studying the genetic basis of adverse drug reactions

Type B adverse drug reactions (ADRs) are often serious, limit the usefulness of drugs that are otherwise effective, and increase the risks of drug development as they often lead to postmarketing withdrawal. There is evidence that susceptibility to at least some Type B ADRs is under strong genetic influence. Identifying genes in which variation influences susceptibility has obvious practical value for genetic testing and might also make it easier to screen molecules likely to cause ADRs at an early stage of the drug development process. Research in this area is hampered by the lack of a resource in which to study genetic determinants of susceptibility to Type B ADRs. As serious Type B ADRs are rare, case-control designs are the most frequently-used approach. The EUDRAGENE collaboration seeks to develop a resource using an international collaboration. This will provide a basis for adverse drug susceptibility genome association-wide studies using tag single nucleotide polymorphisms, or a direct approach using putative functional polymorphisms.     

Adverse reactions of anti-tuberculosis drugs in hospitalized patients: incidence, severity and risk factors

BACKGROUND: Tuberculosis (TB) has been a common chronic infectious disease in human communities. Besides disease-related complications, there could be serious adverse reactions due to anti-tuberculosis (anti-TB) drug therapy. OBJECTIVES: To assess the incidence and severity of adverse drug reactions (ADRs) induced by anti-TB drugs. To determine possible covariates associated with detected ADRs. METHODS: All patients with respiratory TB admitted to a teaching hospital who received anti-TB drugs during the research period entered the study and were monitored for ADRs. Socio-demographic and medical history of patients were used as independent covariates. The relationship between independent covariates with frequency and severity of ADRs was analysed using multivariate logistic regression. Preliminary analyses of the Mann-Whitney, Chi-square, Kruskal-Wallis and the Fisher's exact tests were applied to determine factors unlikely associated with the independent variables. RESULTS: Among 204 patients admitted, there were 92 patients (45.1%) with ADRs induced by anti-TB drugs. Patients with a previous history of anti-TB drugs usage (OR = 5.81, 95% confidence interval [95%CI]: 1.31-25.2), patients with a history of drug allergy (OR = 6.68, CI: 1.28-36.2), those from Afghani ethnic (OR = 4.91, 95%CI: 1.28-18.30) as well as smoker patients with concurrent diseases (OR = 19.67, CI: 1.24-341.51) had a higher rate of ADR incidence. Being female (OR = 1.63, 95%CI: 1.96-36.40) and having previous history of ADR (OR = 17.46, 95%CI: 1.96-20.42) were identified as risk factors. CONCLUSION: Anti-TB drugs could cause severe and frequent adverse effects. Females, those with a previous history of ADRs to anti-TB drugs and Afghani patients, should be considered as high-risk groups.