华法林的相互作用及其安全应用

华法林为香豆素类口服抗凝药,临床上应用越来越广泛,但它与许多药物和食物同时服用均会发生相互作用,从而影响抗凝效果。本文对华法林与西药、中草药和食物的不良相互作用进行概述,以期能为临床安全用药提供参考依据。     

中药对华法林作用的影响及机制概述

华法林是临床常用的一种香豆素类口服抗凝药,具有蛋白结合率高、依赖细胞色素P450酶代谢及治疗窗窄等特点,易与其他药物发生相互作用,造成患者出血风险增加或抗凝治疗不足等严重后果。中药在治疗心脑血管疾病等方面具有独特的优势,临床应用广泛,与华法林合用的机会较多。本文根据已有的实验研究和临床案例报道,分别对单味中药及中药复方制剂对华法林抗凝作用的影响及相关机制进行了综述和探讨,以期为临床合理用药和相关研究提供参考。     

遗传多态性对华法林临床用量的影响

华法林是临床上应用广泛的香豆素类口服抗凝药,主要用于预防和治疗多种血管栓塞类疾病。华法林主要通过抑制维生素K的循环利用,从而产生药理作用,并主要由细胞色素P450酶代谢后,经肾排出体外。但华法林治疗窗较窄,个体及种族差异较大,药物不良反应严重,易受人体的多种因素影响,其中遗传多态性居于主要地位。本文将着重从遗传多态性方面入手,阐述遗传因素对华法林临床用量的影响,以期为临床制定华法林的个体化给药方案提供参考。     

华法林药物基因组学研究及临床应用进展

华法林是临床上常用于治疗血栓性疾病的一种香豆素类口服抗凝药,具有抗凝和溶栓的双重作用.华法林血浆药物浓度和疗效存在明显的个体差异和种族差异,如何在临床安全、合理使用华法林长期以来是许多研究者关注的重点和难点.文中从药物基因组学角度阐述导致华法林维持剂量个体间差异的原因,综述CYP2C9和VKORC1等基因的遗传变异对华法林药物反应差异的影响,并介绍国内外基于药物基因组学研究结果结合临床数据构建华法林维持剂量模型的最新临床应用进展,为个体化治疗提供了新的视角.     

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。     

临床药师参与华法林治疗的药学监护模式

目的：探讨应用华法林抗凝治疗过程中临床药师进行药学监护的模式及必要性。方法：通过几个典型病例,对华法林抗凝治疗患者的药学监护内容进行分析和讨论。结果：临床药师经对国际标准化比率的监测,发现了华法林抗凝作用的多个影响因素,因此在治疗过程中应对其进行严密的药学监护,以提高患者长期抗凝治疗的安全性。结论：临床药师应从个体化角度出发,开展用药监护及宣教工作,合理应用华法林抗凝,提高患者的用药依从性及自我监测、自我调整能力。     

华法林的基因组学研究进展

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生，如何合理使用已经成为一个难题。近年来随着分子生物学的快速发展，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使用中的国内外最新进展，为华法林个体化使用提供参考依据。     

华法林临床应用研究概况

华法林(warfarin)是20世纪40年代美国Wisconsin大学合成的香豆素类口服抗凝血药,主要用于血栓栓塞疾病.临床常以凝血酶原时间(RT)及国际标准化比率(INR)作为其抗凝监测指标.抗凝过度与不足都能引起严重的并发症.许多因素可影响患者对华法林的反应,为了临床更好地了解、使用本药物,本文对近几年的有关报道综述如下.     

住院患者华法林发放的不安全因素分析与对策

临床上常用抗凝药物预防与治疗心血管、骨科术后的多种血栓性、缺血性等疾病,抗凝药物中以香豆素类的华法林应用较多。华法林作用时间长、服用方便、不良反应相对小且可控,价格低廉,因而广泛应用于临床[1]。华法林虽是抗凝治疗的     

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。     

Microbial models of mammalian metabolism: production of novel alpha-diketone metabolites of warfarin and phenprocoumon using Aspergillus niger

1. The coumarin anticoagulants warfarin and phenprocoumon were metabolized by Aspergillus niger via oxidative ring cleavage to yield the corresponding alpha-diketone metabolites. 2. Structural identification was based upon physical, spectral, and chromatographic comparisons of isolated metabolites and synthetic standards generated by the oxidative cleavage of warfarin or phenprocoumon with pyridinium chlorochromate. 3. This pathway of metabolism has been previously observed for coumarin anticoagulants in mammalian systems.     

The pharmacogenetics of coumarin therapy

Vitamin K antagonists (coumarins) are widely-used oral anticoagulants for the prevention of venous thromboembolism and strokes. Wide inter-individual variation in dose response and frequent bleeds characterize the initiation of coumarin therapy. Over the past 10 years both genetic and nongenetic determinants of coumarin dose response have been identified. A comprehensive pharmacogenetics approach to warfarin therapy has the potential to improve the safety and efficiency of warfarin initiation.     

Microbial Models of Mammalian Metabolism: Production of Novel α-diketone Metabolites of Warfarin and Phenprocoumon Using Aspergillus Niger

1. The coumarin anticoagulants warfarin and phenprocoumon were metabolized by Aspergillus niger via oxidative ring cleavage to yield the corresponding α-diketone metabolites.

2. Structural identification was based upon physical, spectral, and chromatographic comparisons of isolated metabolites and synthetic standards generated by the oxidative cleavage of warfarin or phenprocoumon with pyridinium chlorochromate.

3. This pathway of metabolism has been previously observed for coumarin anticoagulants in mammalian systems.     

Genital necrosis secondary to warfarin therapy

Several adverse dermatologic effects have been reported with the use of warfarin. Among these is the rare complication of drug-induced necrosis. Approximately 150 cases had been reported by 1976, and a review of the literature since 1943 revealed only 4 reported cases of penile necrosis. We present the fifth case of genital necrosis reported with coumarin anticoagulants and the third such case associated with warfarin.     

Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin,acenocoumarol and phenprocoumon

Coumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon are frequently prescribed oral anticoagulants to treat and prevent thromboembolism. Because there is a large inter-individual and intra-individual variability in dose–response and a small therapeutic window, treatment with coumarin derivatives is challenging. Certain polymorphisms in CYP2C9 and VKORC1 are associated with lower dose requirements and a higher risk of bleeding. In this review we describe the use of different coumarin derivatives, pharmacokinetic characteristics of these drugs and differences amongst the coumarins. We also describe the current clinical challenges and the role of pharmacogenetic factors. These genetic factors are used to develop dosing algorithms and can be used to predict the right coumarin dose. The effectiveness of this new dosing strategy is currently being investigated in clinical trials.     

Current options in the prevention of thromboembolic disease

Significant advances in the pharmacological prophylaxis of venous thromboembolism have occurred since warfarin and unfractionated heparin were introduced for this indication nearly 60 years ago. Despite these advances, coumarin derivatives such as warfarin remain the only orally active anticoagulants available for prophylaxis in venous thromboembolism. Although administered orally, coumarin derivatives are not convenient to use, because they have narrow therapeutic indexes and require routine coagulation monitoring and dose adjustment. This is inconvenient for patients and physicians and costly for the healthcare system. Low-molecular-weight heparins, which are administered in fixed or weight-adjusted doses and do not require monitoring, are widely used for the prevention of venous thromboembolism in patients in both the hospital and the outpatient setting. However, these drugs must be given subcutaneously, which can be difficult for outpatients and resource-intensive for in-hospital use. Likewise, fondaparinux, the synthetic pentasaccharide, must be administered subcutaneously. Consequently, there remains a need for new orally active anticoagulants that can be given in fixed doses and do not have a narrow therapeutic index, so that coagulation monitoring is unnecessary. Because such agents would be more convenient for patients and physicians, they would probably expand the use of prophylaxis in venous thromboembolism in those at risk, and would simplify treatment of patients with established venous thromboembolism.     

Effect of acetaminophen on international normalized ratio in patients receiving warfarin therapy

Warfarin is known to have extensive interactions with many classes of drugs. The literature suggesting a relevant interaction between acetaminophen and warfarin is inconsistent. Considering the ubiquitous use of acetaminophen, a review of the effects on international normalized ratio (INR) in patients taking warfarin was necessary. Thus, we performed a search of the PubMed (1966-November 2010) and International Pharmaceutical Abstracts (1970-November 2010) databases to review the available literature addressing an acetaminophen-warfarin interaction and its possible mechanisms. A sample of case reports, in addition to all English-language studies were evaluated, and relevant references were examined for additional articles. Reports of nonwarfarin coumarin anticoagulants were excluded. Published documentation reporting an interaction between acetaminophen and warfarin is limited. Small prospective studies of various designs and case studies describe aberrant INR results in patients using acetaminophen while receiving warfarin. These INR elevations typically involved acetaminophen ingestion of at least 2 g/day for several consecutive days. In several small prospective studies, INR results were elevated to a statistically significant extent that would require a change in warfarin dosing and monitoring in clinical practice. The mechanism for this interaction remains to be elucidated yet is suggested to occur through alterations in hepatic metabolism. The use of moderate-to-high doses of acetaminophen while receiving warfarin results in supra-therapeutic INRs in some patients. The characteristics that may predispose a patient to this interaction are unclear, yet the widespread use of acetaminophen calls for enhanced clinician awareness and reinforcement of patient education about this interaction.     

凝血Xa因子直接抑制剂的研究进展与临床应用评价

目的：抗凝治疗是心房颤动药物治疗的核心,但鉴于目前临床应用的传统抗凝血药存在的局限性,一类起效快速、选择性高、作用直接抑制凝血Xa因子的药物应运而生,为临床抗凝治疗提供了更多的选择。本文总结凝血Xa因子直接抑制剂的研究进展与临床评价。方法：采用国内、外文献分析方法。结果与结论：相对于华法林而言,凝血Xa因子直接抑制荆可更特异地抑制血栓形成,抗凝作用起效快,无需监测凝血指标和调整剂量,所致出血风险低,使抗凝作用由多靶点向单靶点迈进,成为临床一线重要的抗凝血药。     

Spectroscopic study of the interaction of coumarin anticoagulant drugs with polyvinylpyrrolidone

The interaction of coumarin anticoagulants with polyvinylpyrrolidone (PVP) was investigated using a fluorescence technique. The fluorescence intensities of warfarin and phenprocoumon were greatly enhanced following binding to PVP, while the fluorescence of 4-hydroxycoumarin was little enhanced in the presence of PVP. The enhanced fluorescence of warfarin and phenprocoumon bound to PVP can be explained by their incorporation into the hydrophobic environment in the PVP and by a decrease in the internal rotation of the alpha-substituted benzyl group in the drugs. The binding parameters of warfarin and phenprocoumon were estimated by the Klotz method; the binding constants for phenprocoumon and warfarin were found to be 2.6 X 10(4) and 2.2 X 10(4) M-1, respectively. The 13C-NMR measurements suggest the lactone moiety in the 4-hydroxycoumarin and the substituted benzene ring play an important role in the binding to PVP.     

我院2013年1-6月住院患者华法林应用情况分析

目的:为提高华法林的临床合理用药水平提供参考。方法:统计2013年1-6月我院住院患者服用华法林的情况,分析使用华法林的患者的疾病状态及合并用药对华法林作用的影响。结果:2013年1-6月,我院住院患者中共有179例服用华法林,分布于全院13个科室、24个病房;应用华法林的适应证共14项;本调查中涉及的可能与华法林存在相互作用的合并用药共56种。结论:华法林广泛应用于我院多个科室的住院病房,应用华法林的患者多数病情复杂、合用多种药物。临床在应用华法林时需要综合患者疾病和用药情况,密切监测患者的出、凝血情况,给予患者个体化的华法林用药方案。