抗血小板药物防治冠心病的研究

抗血小板药物防治冠心病的研究魏文利黄守坚１（中山医科大学卫生部辅助循环重点实验室；１药理教研室，广州５１００８９）中国图书分类号Ｒ９７２；Ｒ５４１．４冠心病的发生发展与血小板功能异常密切相关，高血脂、糖尿病、吸烟及精神压力等因素触发或加重冠心病急性心...     

抗血小板药物的研究进展

抗血小板药可抑制血小板聚集,进而抑制动脉中血栓形成,是防治动脉血栓性疾病的重要治疗药物。随着心脑血管疾病发病率逐年增加,临床对抗血小板药物的应用、疗效和不良反应的研究越来越多。为获得更好的抗血小板效果,目前临床急需一种抗血小板药物或药物组合,能达到提高抗血小板效果,同时降低药物副作用、减少药物抵抗发生概率、降低术后出血再栓塞风险的目的,以适合更广泛的人群。按药物作用机制,抗血小板药分为如下几类：①环氧酶抑制剂：代表药物阿司匹林,具有强烈的抗血小板聚集作用;②二磷酸腺苷受体拮抗药（ADPR - A）：代表药物噻氯匹定、氯吡格雷、普拉格雷;③血小板膜糖蛋白（GP）Ⅱb／Ⅲa 受体抑制剂：代表药物阿昔单抗、依替非巴肽、替罗非班;④磷酸二酯酶抑制剂：代表药物双嘧达莫、西洛他唑,通过激活血小板腺苷环化酶（cAMP）或抑制磷酸二酯酶对 cAMP 的降解作用,使血小板内 cAMP 浓度增高而产生抗血小板作用;⑤5-羟色胺受体拮抗剂：代表药物沙格雷酯,可以特异性地与5- HT2受体结合,抑制血小板的聚集。本文对近年较有潜力的或已上市的几类抗血小板药物的临床研究进展进行综述。     

抗血小板药物作用靶点的研究进展

目的:为新型抗血小板药物的研发提供参考。方法:以"抗血小板""血小板黏附""血小板活化""血小板聚集""作用机制""Antiplatelet""Platelet adhesion""Platelet activation""Platelet aggregation""Mechanism"等为中英文关键词,在中国知网、万方数据、Pub Med等数据库中组合查询2003年1月-2020年2月发表的相关文献,就血小板参与血栓形成过程中各个级联反应相关的重要信号通路及其作用,以及以各个分子信号为靶点的药物研究进展进行综述。结果与结论:共检索到相关文献3 863篇,其中有效文献52篇。目前,抗血小板药物作用靶点包括血小板黏附信号靶点[如膜糖蛋白(GP)Ⅰb-Ⅸ-Ⅴ与血管性血友病因子的相互作用、GPⅥ与胶原的相互作用]、血小板活化信号靶点[二磷酸腺苷(ADP)受体通路、磷酸二酯酶相关信号、磷脂酰肌醇-3-激酶信号、血栓素相关信号)、血小板聚集靶点[GPⅡb/Ⅲa、蛋白酶激活受体]、磷脂酶C、P-选择素、血小板活化因子等。这些靶点和信号通路参与了血小板黏附、激活、聚集过程以及促进了血小板相关血栓的形...     

抗血小板聚集药物研究概况

抗血小板聚集药物是通过抑制血小板的异常黏附、聚集和释放反应以抵抗血栓形成和动脉粥样硬化的发展.     

抗血小板聚集药物研究概况

抗血小板聚集药物是通过抑制血小板的异常黏附、聚集和释放反应以抵抗血栓形成和动脉粥样硬化的发展。     

抗血小板药物的临床应用

<正> 血小板在血栓形成、动脉粥样硬化的发生发展过程中起着重要作用。抗血小板药广泛应用于临床心脑血管疾病的预防和治疗。下面对抗血小板药物的作用机理及临床应用作一综述。1 抑制血小板花生四烯酸代谢的药物代表药物是阿司匹林。此药于1897年合成,1899年作为解热镇痛药问世并广泛应用于临床。1968年Zucker和Weiss首先观察到阿司匹林有体外     

浅谈抗血小板药物治疗监测方法

目前,抗血小板药物监测已经越来越受到临床的重视,对治疗效果的监测往往体现在对血小板功能的监测上,本文总结了临床常用的监测血小板功能的试验,介绍了一些新的监测抗血小板药物手段。     

抗血小板药物的临床应用及其发展趋势

血小板在冠状动脉血栓形成的起始中起关键性的作用。血管壁的损伤使内皮下基质暴露，血小板通过糖蛋白(glycoprotein，GP)Ib与冯利威布兰德因子(von-Willebrand factor，vWF)结合，GP Ia与胶原结合及其他黏附分子的相互作用结合到损伤处，促进凝血酶、二磷酸腺苷(ADP)、胶原和血栓素A2(TXA2)等释放而被活化。     

抗血小板药物研究概况

血小板在动脉硬化发病、血栓尤其是动脉血栓性疾病形成过程中起着十分重要的作用。抗血小板药物是通过抑制血小板的异常粘附、聚集和释放反应以抵抗血栓形成和动脉粥样硬化的发展。当前 ,对此类药物的研究十分活跃 ,本文对此作一简述。1　酚酸类化合物刘岱琳等[1] 通过对 19种酚酸类化合物体外抗ＡＤＰ诱导兔血小板聚集活性的测定 ,发现没食子酸、阿魏酸、对羟基桂皮酸、琥珀酸、酒石酸、壬二酸、丹皮酚等有明显抑制血小板聚集作用 ,其抗血小板聚集活性与结构的关系为 :邻三酚羟基的酚酸比邻二酚羟基的酚酸活性强 ;而脂肪二酸类比酚酸类化合…     

抗血小板药物致胃肠道出血的防治进展

抗血小板聚集是血栓栓塞性疾病防治的重要措施,但由抗血小板药物引发的胃肠道损害临床常见。本文就阿司匹林与氯吡格雷等抗血小板药物导致胃肠道出血的研究现状及其防治的研究进展作一综述。     

Comparative effectiveness of different antiplatelet agents at reducing TNF-driven inflammatory responses in a mouse model

Antiplatelet drugs are conventionally used as treatments because of their anti-coagulation functions. However, their pleiotropic effects are of great significance to the treatment of ischaemic cardiovascular diseases. Many studies have reported that an excessive amount of inflammation driven by tumour necrosis factor (TNF) is closely related to the prevalence of atherosclerosis. As the drug selection criteria and evaluation methods related to the anti-TNF activity of antiplatelet drugs remain limited, our investigation of these drugs should prove beneficial. In this study, we compared the anti-TNF activity of three antiplatelet agents, namely clopidogrel, sarpogrelate, and cilostazol, using the TNF-induced inflammatory mouse model. After the oral administration of these drugs, acute inflammation was induced via injection of lipopolysaccharide (LPS) or D-galactosamine (D-gal) and TNF. Serum TNF levels, and the mRNA and protein expression levels of TNF in mouse heart tissue, macrophage accumulation in aortic lesions, and mouse survival were analysed to compare the anti-TNF effects of the three antiplatelet agents. Of the three antiplatelet agents, cilostazol significantly reduced the different levels under the most effective observation. In addition, cilostazol was found to attenuate the TNF-stimulated phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) p65 in the aortic vascular smooth muscle cell line, MOVAS-1 and the D-gal plus TNF-challenged heart tissue of mouse. Therefore, cilostazol is the most ideal of the three antiplatelet drugs for the treatment of TNF-mediated inflammatory disorders.     

Chalcones as potent antiplatelet agents and calcium channel blockers

In an effort to continually develop potent antiplatelet agents with vasorelaxing and antiinflammatory actions, a novel series of antiinflammatory chalcones was continually screened to evaluate their antiplatelet and vasorelaxing effects. Their structure–activity relationships and mode of action were discussed and characterized. A novel series of antiinflammatory chalcones was studied on antiplatelet effect in rabbit washed platelets and human platelet‐rich plasma (PRP) and vasorelaxing effect in rat thoracic aorta. Arachidonic acid‐induced platelet aggregation was potently inhibited by almost all the chalcone derivatives and 13–15 also had a potent inhibitory effect on cyclooxygenase. The selective chalcones 12–16 tested in human PRP significantly inhibited secondary aggregation induced by adrenaline. In rat thoracic aorta, most of chalcones at high concentration significantly depressed the contractions induced by Ca²⁺ (1.9 mM) in high K⁺ (80 mM) medium and the phasic and tonic contractions caused by norepinephrine (3 μM). In the rat thoracic aorta, the phenylephrine‐ and high K⁺‐induced ⁴⁵Ca²⁺ influx were both inhibited by a selective chalcone derivative, 14 . These results indicate that the antiplatelet actions of chalcones are mainly mediated through the suppression of cyclooxygenase activity and reduced thromboxane formation and their inhibitory effects on the contractile response caused by high K⁺ and norepinephrine in rat thoracic aorta are mainly due to inhibition of Ca²⁺ influx through both voltage‐dependent and receptor‐operated Ca²⁺ channels. Drug Dev. Res. 53:9–14, 2001. © 2001 Wiley‐Liss, Inc.     

Clinical trials of an antiplatelet agent,ticlopidine, in diabetes mellitus

Summary

At present there is no simple, reliable and noninvasive method for monitoring progression and improvement in diabetic microangiopathy. However; some diabetic patients with severe microvascular complications show a fairly specific pattern of impaired left ventricular function (abnormal relaxation, cavity filling and wall thinning) and abnormalities of haemorheology (increased viscosity, erythrocyte rigidity and beta-thromboglobulin and decreased threshold for platelet ADP aggregation). A single-blind, 6-months’ crossover study of an antiplatelet agent, ticlopidine, was conducted in 20 diabetics with clinical evidence of microvascular disease. Response to therapy was monitored by digitised M-mode echocardio-graphic analysis of left ventricular diastolic function and haemorheology. All patients had abnormal basal values with no significant change during the 3-month placebo run-in period but, although significant alterations in viscosity, erythrocyte deformability, beta-thromboglobulins and ADP threshold were observed, no change in left ventricular function was detected. It is concluded that, while it may be possible to alter abnormal haemorheology in diabetes, there was no change in one parameter of microvascular end-organ damage.     

2005-2006年上海市东方医院抗血小板药物用药分析

目的：对2005-2006年上海市东方医院抗血小板药物用药合理性进行调查分析,为合理用药提供参考.方法：对抗血小板药物的品种、数量以及与阿司匹林存在药物相互作用的药物进行统计,并对一个使用阿司匹林出现不良反应的病例进行分析.结果：本院抗血小板药物的应用仍存在一些问题.结论：临床需进一步规范使用抗血小板药物.     

冠状动脉粥样硬化性心脏病患者抗血小板治疗的调查分析

目的：调查了解某院冠状动脉粥样硬化性心脏病（以下简称"冠心病"）患者口服抗血小板药物治疗情况,进一步规范医院抗血小板治疗的应用。方法：回顾性调查2015年8月1日-2016年7月31日于某院心血管内科住院的冠心病患者共832例,统计患者基本情况、既往病史、冠心病类型、口服抗血小板药物应用情况和药物品种数发生调整的原因等。结果：冠心病患者出院时口服抗血小板药物治疗品种数发生调整的情况主要为减少抗血小板药物品种数（占比99.14%）,用药品种数减少的主要原因为患者/家属用药依从性差（102例,占比43.22%）,其次为患者具有极高出血风险（55例,占比23.30%）和高出血风险（48例,占比20.34%）。结论：患者/家属用药依从性差和对出血风险的过度担心制约着冠心病患者的规范化抗血小板治疗,临床药师应合理利用药物治疗数据来开展更具针对性的药学服务,确保患者安全有效的应用抗血小板药物。     

Pharmacodynamic properties of antiplatelet agents: current knowledge and future perspectives

Platelets play an important role in atherothrombotic disease. The currently available antiplatelet drugs target key steps of platelet activation including thromboxane A₂ synthesis, ADP-mediated signaling, and glycoprotein IIb/IIIa-mediated platelet aggregation. The improvement of our understanding on the pharmacokinetic and pharmacodynamic characteristics of these drugs enables the tailoring of the most appropriate anti-thrombotic therapy to the individual patient and risk situation in the daily clinical practice. However, current antiplatelet therapies are associated with increased bleeding risk. Thus, further research on platelet functions may give rise to numerous new antiplatelet agents with high anti-thrombotic efficiency and low adverse hemorrhagic side effects.     

金银花及其有机酸类化合物的体外抗血小板聚集作用

目的:观察金银花及其有机酸类化合物的体外抗血小板聚集作用及作用强度。方法:应用比浊法测定金银花及其单体有机酸类化合物的体外抗ADP诱导的血小板聚集作用,通过系列浓度,用Logit法计算50%聚集抑制浓度(IC50)。结果:金银花水提物有抗ADP诱导的血小板聚集作用,其IC50值为0.028g.mL-1,其含有的有机酸类化合物绿原酸的同分异构体(2个)、咖啡酸、异绿原酸类(3个)IC50分别为0.028 6,1.707,2.411,0.026,0.328,0.539g.L-1。结论:金银花及其有机酸类化合物绿原酸的同分异构体、咖啡酸、异绿原酸类均具有较强的抗血小板聚集作用。     

抗菌药物致血液系统不良反应分析

近年来,随着抗菌药物在临床上的广泛应用,抗菌药物相关不良反应也越来越引起人们的关注。其中,由于抗菌药物所引起的血液系统不良反应严重影响了患者的身体健康和医生的药物选择。例如,部分β-内酰胺类抗生素可以引起凝血功能障碍和溶血性贫血,氯霉素、磺胺等可以引起再生障碍性贫血,利奈唑胺可以引起血小板减少和贫血等。正确认识各种抗菌药物所引起的血液系统不良反应及其机制,对于临床抗菌药物的选择具有重要意义。本文针对临床常见抗菌药物引起的血液系统不良反应及其机制进行综述,以期为临床抗菌药物的选择提供参考。