抗凝药物华法林的安全应用

华法林为临床上最常用的抗凝药物。本文综述了华法林的作用机制、药代动力学、治疗作用、不良反应及影响华法林抗凝效果的因素,以期能为临床安全使用华法林提供参考.     

华法林联合新型抗抑郁药应用研究进展

抗凝药华法林安全窗狭窄,最常见不良反应为各种出血。华法林与许多药物有相互作用,抗抑郁药可增强华法林抗凝作用,增加出血风险。临床使用华法林的患者如果合并抑郁障碍或焦虑障碍而需要使用抗抑郁药时,临床医生会面临两难的选择。本研究试图从药动学和遗传学变异角度解析两类药物的联合使用,为临床合理用药提供帮助。     

华法林基因导向的个体化抗凝研究进展

华法林是临床广泛使用的抗凝药，但其疗效存在明显个体差异，其中基因多态性是导致华法林剂量差异主要影响因素。本文查阅相关文献，综述与华法林剂量相关的基因，为临床华法林个体化应用提供参考。     

华法林药物基因组学的研究推动其个体化医疗的进程

药物基因组学可以帮助人们更好地认识药物与机体之间的相互作用。华法林是临床上广泛使用的香豆素类口服抗凝血药,其狭窄的抗凝治疗指数范围和抗凝不当所致的并发症一直困扰着临床医师,如何合理使用已经成为一个难题。近年来,随着药物基因组学的快速发展,研究发现药动学和药效学多个相关基因的多态性造成了个体差异,影响了华法林的使用剂量。本文综述了药物基因组学研究在华法林用药中的国内外最新进展,为华法林个体化医疗提供参考依据。     

新型口服抗凝药物在房颤治疗及预后方面的研究进展

华法林是防治房颤卒中最有效抗凝药物。出血、频繁监测INR值等缺点限制了华法林临床使用率。新近一些新型口服抗凝药物的研究不断涌现,许多研究结果表明这些新型口服抗凝药物在预防卒中的作用中不劣于华法林,且出血风险可能较华法林低,故有望取代华法林这一传统抗凝药。本文系统回顾近年有关口服抗凝药的相关研究,并将这些研究进展综述如下。     

香豆素类抗凝药的临床评价与合理应用

目的：对香豆素类抗凝药的临床应用现状进行评价和研究。方法：查阅国内外近年来的相关文献,对香豆素类抗凝药的代表药物华法林的药学基础、临床应用及研究进展进行总结和分析。结果及结论：随着医生和患者对华法林的认识不断加深,华法林将在口服抗凝治疗中发挥更加积极的作用;国内对华法林的使用有待更加规范化。     

华法林临床应用及出血不良反应介绍

华法林（Warfarin）是香豆素类口服抗凝血药,因狭窄的抗凝治疗指数范围和抗凝不当所致的出血并发症一直妨碍其临床抗凝治疗。本文汇总近年来国内外华法林临床治疗使用情况及其安全性评价,探讨华法林治疗中致出血的机制,优化其治疗方案,为临床医师提供参考,保障临床用药安全。     

临床药师对心血管疾病患者进行华法林药学监护切入点的探讨

目的:探讨临床药师为心血管疾病患者应用华法林实施药学监护的切入点。方法:通过分析影响华法林抗凝作用的因素及患者在华法林抗凝治疗中容易出现的问题开展药学服务,指导其规范使用抗凝药华法林。结果与结论:影响华法林抗凝作用的因素较多,药师应积极开展合理有效的药学服务,以避免不良事件发生,对提高患者生活质量具有重要意义。     

华法林抗凝过程中不良反应及其影响因素分析

华法林(warfarin)是临床上最常用的口服抗凝血药,用于治疗和预防各种血栓栓塞性疾病。华法林治疗窗窄,个体差异大,因而剂量要求各有不同,并且用药不足会达不到抗凝效果,而用药过量又会增加出血风险。华法林相关不良事件中最常见的即为出血反应。本文汇总了近年来关于华法林出血性研究,分析了影响出血的相关因素以及其作用机制,期望能为临床安全使用华法林进行抗凝治疗提供参考。     

华法林抗凝血作用及影响因素分析

目的探讨华法林抗凝作用的影响因素,促进华法林合理使用。方法查阅国内外文献,阐述华法林抗凝作用机制和作用特点,分析华法林抗凝作用的影响因素。结果华法林抗凝作用显著,使用方便,但安全范围狭窄,易受遗传、疾病、药物及食物的影响。结论充分认识华法林抗凝作用影响因素,实施个体化给药,提高华法林抗凝疗效,减少出血并发症的发生。     

Ethical perspectives on pharmacogenomic profiling in the drug development process

Pharmacogenomics, which is a field that encompasses the study of genetic polymorphisms that underlie individual differences in drug response, is rapidly advancing. The potential for the widespread use of pharmacogenomics in the drug development process merits an examination of its fundamental impact on clinical-trial design and practice. This article provides a critical analysis of some of the issues that pertain to pharmacogenomics in the drug development process. In particular, four areas will be discussed: clinical-trial design; subject stratification; some new social risks; and economic concerns. Recommendations are offered for addressing the issues that are discussed and anticipating the regulatory needs for pharmacogenomics-based trials.     

An automatic dose dispenser for microtablets--a new concept for individual dosage of drugs in tablet form

A new concept for individualising the dosage of drugs in solid form is presented. The principle is based on the use of standardised units (microtablets), each containing a subtherapeutic amount of the active ingredient. The required dose is fine-tuned by counting out a specific number of these units. The microtablets are counted electronically from the attached cassette by the automatic dispensing device. The individual dose is set and the dispenser counts and delivers the correct number of microtablets. The usefulness of the automatic dispenser concept and acceptability of the apparatus were evaluated in patients with Parkinson's disease (PD). After initial instruction on use of the dispenser, 20 patients operated it themselves. All patients were generally satisfied with their management of the automatic dispenser and most would be happy to use the device again. Further technical development is required before use in clinical practice, but the current prototype may be acceptable for some patients. It is concluded that the final version of the automatic dose dispenser concept will offer potential for improvement of drug administration for patients with PD or other diseases requiring individual dosage.     

The usage of antibiotics in Russia and some countries in Eastern Europe.

The patterns of antibiotic use in 1998 in Russia and some other countries in Eastern Europe (Belarus, Poland, Slovakia, Hungary) were studied. Poland, Slovakia and Hungary were "more modern" users of antibiotics, consuming new and expensive drugs. Russia and Belarus were "conservative" having a lower level of total consumption and using lesser quantities of penicillins, cephalosporins, macrolides, quinolones, carbapenems but greater amounts of aminoglycosides and chloramphenicol. It is essential for "conservative" countries to establish a national surveillance system of antibiotic consumption to monitor the development of bacterial resistance to antimicrobial agents and to monitor individual antibiotic use.     

Mapping training: the transfer of a cognitive technology for improving counseling

To provide information that will reduce the gap between research and practice, the transfer of a complex drug abuse counseling technology is examined. This technology, cognitive mapping, is a graphic tool shown to effectively facilitate communication and problem solving in group and individual counseling sessions. Unlike some techniques, mapping requires substantial counselor time, effort, and expertise to learn and to use. This article briefly describes the development and evolution of mapping and supporting research. It then focuses on our efforts to develop mapping training that will facilitate use of this evidence-based technique in drug abuse treatment. Major training and transfer pitfalls are noted, and strategies for successful training are recommended.     

Prediction of treatment outcomes in major depressive disorder

Improving the treatment of major depressive disorder will require identification of moderators that predict differential outcomes across treatments at the level of the individual patient, referred to as precision medicine. Currently, there are no biological measures demonstrated to enhance treatment selection accuracy although there are some clinical variables that have prognostic value. Several recent studies comparing treatments with differing mechanisms of action have identified potential moderators that may eventually be used in precision medicine approaches. Genetic combination tests, systemic inflammation, electroencephalography and neuroimaging, in particular, show significant potential for near-term development as clinically meaningful moderators for use in treatment selection. Ultimately, combinations of moderators may provide the greatest level of precision in selecting optimal treatment approaches for individual depressed patients.     

Nonclinical vehicle use in studies by multiple routes in multiple species

The laboratory toxicologist is frequently faced with the challenge of selecting appropriate vehicles or developing utilitarian formulations for use in in vivo nonclinical safety assessment studies. Although there are many vehicles available that may meet physical and chemical requirements for chemical or pharmaceutical formulation, there are wide differences in species and route of administration specific to tolerances to these vehicles. In current practice, these differences are largely approached on a basis of individual experience as there is only scattered literature on individual vehicles and no comprehensive treatment or information source. This approach leads to excessive animal use and unplanned delays in testing and development. To address this need, a consulting firm and three contract research organizations conducted a rigorous data mining operation of control (vehicle) data from studies dating from 1991 to present. The results identified 65 single component vehicles used in 368 studies across multiple species (dog, primate, rat, mouse, rabbit, guinea pig, minipig, chick embryo, and cat) by multiple routes. Reported here are the results of this effort, including maximum tolerated use levels by species, route, and duration of study, with accompanying dose limiting toxicity. Also included are basic chemical information and a review of available literature on each vehicle, as well as guidance on volume limits and pH by route and some basic guidance on nonclinical formulation development.     

Caffeine:

Recent investigations of caffeine abuse have questioned the indiscriminant use of this commonly accepted drug. In some individuals, chronic excessive caffeine consumption leads to the development of caffeinism, a syndrome which includes increased anxiety, depression, frequency of psychophysiological disorders, and possibly degraded performance. This paper reviews the research demonstrating the abuse potential of caffeine. Special attention has been given to those factors which mediate the wide individual differences in consumption patterns, susceptibility to abuse, and the varied psychological and physiological responses to this drug. While the development of caffeine abuse is probably best viewed as an idiosyncratic process, general guidelines for the recognition of potential abuse, and caffeinism proper, are offered.     

A Safety Monitoring Procedure for a Clinical Drug Development Program,with Application to the Assessment of a Novel COX-2 Inhibitor

Formal safety monitoring procedures are well-developed for use in individual clinical trials and provide valuable guidance to Independent Data Monitoring Committees (IDMCs). Less has been written about procedures for use over the whole of a drug development program. It is becoming common for a single IDMC to be appointed for a whole series of studies involving a single compound. While each study will have its own goals in terms of efficacy, safety, or both, there is the potential for all of them to contribute to an emerging picture of safety. Indeed, an IDMC overseeing several studies will need to integrate the data coming from each and a formal pre-defined approach can be a valuable aid. Formal procedures are especially relevant in situations where one or two undesirable events are recognized from the outset as being of particular concern. In some cases this might be death, and in the example discussed here it is a cardiovascular event of the type that has been found to be related to certain COX-2 inhibitors. In this paper a design proposal for a safety monitoring procedure for use by an IDMC during the development of a new COX-2 inhibitor will be described.     

A safety monitoring procedure for a clinical drug development program, with application to the assessment of a novel COX-2 inhibitor

Formal safety monitoring procedures are well-developed for use in individual clinical trials and provide valuable guidance to Independent Data Monitoring Committees (IDMCs). Less has been written about procedures for use over the whole of a drug development program. It is becoming common for a single IDMC to be appointed for a whole series of studies involving a single compound. While each study will have its own goals in terms of efficacy, safety, or both, there is the potential for all of them to contribute to an emerging picture of safety. Indeed, an IDMC overseeing several studies will need to integrate the data coming from each and a formal pre-defined approach can be a valuable aid. Formal procedures are especially relevant in situations where one or two undesirable events are recognized from the outset as being of particular concern. In some cases this might be death, and in the example discussed here it is a cardiovascular event of the type that has been found to be related to certain COX-2 inhibitors. In this paper a design proposal for a safety monitoring procedure for use by an IDMC during the development of a new COX-2 inhibitor will be described.     

Pharmacogenomics: The implementation phase

Pharmacogenomics makes use of genetic and genomic principles to facilitate drug discovery and development, and to improve drug therapy. Its goal is to attain optimal therapy for the individual patient. This article analyzes current trends in pharmacogenomics and asks how this new science affects drug development in the pharmaceutical industry and the clinical use of drugs.