心血管药物的新进展(上)

本文总结了心血管药物近年来临床研究的新进展,包括肾上腺素β受体阻滞剂、钙通道阻滞剂、血管紧张素转化酶抑制剂、抗心力衰竭药、抗心律失常药、抗心肌缺血药、抗高血压药、降血脂药、抗血小板药和抗血栓药。提示心血管药物在基础理论指导下,新药品种层出不穷,使心血管疾病的药物治疗发生了重大改观,促进了临床医学的发展。本文有助于医药工作者了解心血管药物的全貌,特别可提供制药厂在开发和研究心血管新药时作参考。     

世界新药研发动向

药物创新是全球医药行业及医药市场快速发展的推动力,在全球创新投入中占有巨大的份额,虽然其研发风险高,但其投资力度仍持续增长。笔者回顾了2006年以来新药研发领域的重大事件,对肿瘤、心血管疾病、糖尿病、艾滋病、多发性硬化症和老年性黄斑变性等常见疾病治疗药物的研究现状进行了总结。     

缓控释技术在药物防治心血管疾病中的应用

缓控释药物在心血管疾病的治疗中起效平稳、释药时间长,具有良好的开发应用前景。本文对近年来国内外心血管疾病的口服缓控释制剂的研究现状进行综述,概述了渗透泵型、骨架型、脉冲型、包衣型、微丸、胶囊及微囊制剂的研究进展,为研发防治心血管疾病的缓控释药物提供参考,对更好地满足患者的用药需求具有积极意义。同时也对心血管缓控释制剂的发展进行了展望。     

抗精神病药物的心血管副作用及其机制的研究进展

近年来,心血管疾病已成为精神障碍患者的主要死因,这引起了国内外学者的广泛关注。多数非典型抗精神病药都会导致显著的代谢不良反应,继而引发心血管疾病。随着抗精神药物的适应证和适应人群的不断扩大,抗精神病药物导致的心血管疾病的机制研究迫在眉睫。越来越多的研究表明,抗精神病药对外周及中枢神经的非特异性的药理作用导致了其心血管副作用,如体位性低血压、心动过速和室性心律失常等,其心血管副作用可能与肾上腺素能受体或胆碱能受体和hERG钾通道的阻断有关,也有可能与自主神经功能受损有关。本次综述旨在结合临床前和临床研究成果,分析并讨论抗精神病药物对心血管系统的直接或间接的影响以及不良反应发生的机制,进而全面了解抗精神病药物对心血管系统的副作用。     

盐酸小檗碱的心血管药理活性研究进展

小檗碱是一种异喹啉生物碱,存在于黄连、黄檗等植物中,临床常用其盐酸盐.盐酸小檗碱具有强心、抗心律失常、内皮保护、心肌保护、降压、抗动脉粥样硬化、糖尿病性心血管疾病治疗等心血管药理活性作用,是一种富有潜力的心血管疾病治疗药物.本文通过对PubMed数据库进行检索,对盐酸小檗碱的心血管药活性研究进行了综述.     

心血管药物的研究进展情况

心血管疾病已成为目前世界发达国家的主要死亡原因。一些发展中国家心血管疾病也逐渐成为威胁生命的头号杀手。心血管药物对增进人类生命健康,改善生活质量有着重大的、特殊的社会意义。自八十年代中期心血管药物就步入其研制开发的黄金阶段。进入九十年代,其主导地位更是不可替代。它是世界范围内用量最多,销售额最大的一类治疗药物。至今一直稳居各类药物之首。生命科学的发展促进了心血药物的发展,反之,心血管药物的发展又促进了生命科学的发展。1 心血管药物现状1.1 抗高血压药:是心血管药物中份额最大的一类。     

2004年美药物研究与开发回顾

开发用于对付在美国日益流行的糖尿病治疗药是美国制药业研究领域中增长最快的部分。根据PB公司的研发指南，在开发不同阶段或已向FDA提出NDA申请的有98个糖尿病治疗药。在十大研究领域中，糖尿病占第7位，并列于10大增长最快的领域中。癌仍然是最大的领域，有545个药物在开发中。抗感染药位居次位（214个），第3位是心血管药（206个）。抗炎药以127个居第4位，余下的依次是呼吸疾病用药第5位（110个）、抗精神病药第6位（107个）、血液病用药第8位、胃肠道药第9位和皮肤病药第10位。     

卵巢癌的治疗药物研究进展

卵巢癌是女性生殖器官常见的恶性肿瘤之一,其死亡率居妇科恶性肿瘤首位,且发病率逐年增加。全球新批准并上市的治疗卵巢癌的药物有贝伐单抗、曲贝替定、人参皂苷以及一些新制剂,处于研发后期的抗卵巢癌药物有奥拉帕尼、西地尼布、nintedanib、trebananib以及一些抗卵巢癌药的新剂型品种等。对近年来上市和处于研发后期的卵巢癌的治疗药物进行了详细介绍,同时对抗卵巢癌药的未来发展方向进行了展望,以期为抗卵巢癌药物的研发提供参考。     

2010新药展望 重磅炸弹减少 小病种创新药纷呈

2010年有望上市的药物异彩纷呈,引人关注。多发性硬化领域将会迎来多种口服治疗药物,结束单一注射的时代。糖尿病、心血管以及疼痛等领域,不乏新型治疗药物入市。各企业的研发重点已从重磅炸弹类产品转向小病种创新药。     

心血管疾病药物利用调查

心血管药物近年来发展较快，60年代发展的β-阻滞药，70年代发展的钙括抗剂，80年代开发的血管紧张素转换酶抑制剂是三个主要系列。近20年来，一些新的抗心律失常药等与上述三个系列药在一起，构成当前治疗心血管疾病的主要药物。由于心血管疾病在人群中的发病率高，故应用广泛。本文随机抽取四川省人民医院1996年5月出院病历379份，对其中使用的β-阻滞剂、钙桔抗剂、硝酸酯类、ACEI、抗心律失常药等5类药物进行药物利用调查，其目的是为了了解医生的用药习惯，发现用药的流行趋势，监测用药的合理性。1方法资料来源：随机抽取四川省人民…     

精神分裂症患者心血管疾病风险因素的研究进展

精神分裂症伴随的躯体疾病尤其是心血管疾病是近年来临床医生和研究人员逐渐关注的领域.了解精神分裂症与心血管疾病之间的关系,减轻精神分裂症患者的疾病负担,提高精神分裂症患者的生活质量,是精神科临床工作的重中之重.该综述的目的是概述精神分裂症患者心血管疾病的相关危险因素及潜在的早期诊断方法和预防措施,并讨论了早期发现和预防精神分裂症心血管疾病发生的潜在可行的方法.尽管精神分裂症患者是罹患心血管疾病的高危人群,但目前仍缺乏针对精神分裂症心血管疾病早期发现和预防的具有共识性的治疗指南.精神分裂症患者合并心血管疾病问题需要更多的临床医生和研究人员关注.     

戒烟药物的心血管不良反应

戒烟可降低心血管疾病发生和死亡风险,是心血管疾病二级预防的重要内容。吸烟是一种慢性成瘾性疾病,戒烟过程中常因戒断症状导致复吸,在戒烟过程中需要心理支持治疗和戒烟药物辅助治疗。许多随机对照临床试验证实,戒烟心理辅导有助于患有心血管疾病吸烟者的戒烟。但很少有临床试验证实戒烟药物在心血管疾病患者应用的安全性及有效性。由于尼古丁替代治疗,以及缓释安非他酮和伐尼克兰均可引起交感神经兴奋,理论上增加心肌作功,提高心肌耗氧量;其中尼古丁替代治疗还可能引起内皮功能障碍,使冠状动脉收缩,心肌供氧量减少,因此,越来越多的研究者开始关注合并心血管疾病吸烟者中戒烟药物应用的安全性。     

Selective targeting of glucagon-like peptide-1 signalling as a novel therapeutic approach for cardiovascular disease in diabetes

Glucagon-like peptide-1 (GLP-1) is an incretin hormone whose glucose-dependent insulinotropic actions have been harnessed as a novel therapy for glycaemic control in type 2 diabetes. Although it has been known for some time that the GLP-1 receptor is expressed in the CVS where it mediates important physiological actions, it is only recently that specific cardiovascular effects of GLP-1 in the setting of diabetes have been described. GLP-1 confers indirect benefits in cardiovascular disease (CVD) under both normal and hyperglycaemic conditions via reducing established risk factors, such as hypertension, dyslipidaemia and obesity, which are markedly increased in diabetes. Emerging evidence indicates that GLP-1 also exerts direct effects on specific aspects of diabetic CVD, such as endothelial dysfunction, inflammation, angiogenesis and adverse cardiac remodelling. However, the majority of studies have employed experimental models of diabetic CVD and information on the effects of GLP-1 in the clinical setting is limited, although several large-scale trials are ongoing. It is clearly important to gain a detailed knowledge of the cardiovascular actions of GLP-1 in diabetes given the large number of patients currently receiving GLP-1-based therapies. This review will therefore discuss current understanding of the effects of GLP-1 on both cardiovascular risk factors in diabetes and direct actions on the heart and vasculature in this setting and the evidence implicating specific targeting of GLP-1 as a novel therapy for CVD in diabetes.     

Vitamin D therapy in cardiac hypertrophy and heart failure

Vitamin D3 is made in the skin, modified in the liver to form 25(OH)D, and then further hydroxylated in the kidney to form the active hormone, 1,25-dihydroxyvitamin D3 (calcitriol). Calcitriol binds to and activates the vitamin D receptor (VDR), a nuclear receptor, to regulate numerous downstream signaling pathways in different cells and tissues. Emerging evidence suggests that VDR plays an important role in modulating cardiovascular, immunological, metabolic and other functions. Data from preclinical, epidemiological and clinical studies have shown that deficiency in VDR activation is associated with an increased risk for cardiovascular disease (CVD). Results from interventional trials using either nutritional vitamin D or VDR agonists (VDRAs) support the idea that VDR activation is beneficial for improving the underlying factors of CVD such as hypertension, endothelial dysfunction, atherosclerosis, vascular calcification, cardiac hypertrophy and progressive renal dysfunction. Furthermore, a majority of chronic kidney disease (CKD) patients die of CVD and VDRA therapy is associated with a survival benefit in both pre-dialysis and dialysis CKD patients. Most of the studies measured serum 25(OH)D as an indication for vitamin D deficiency, which does not truly reflect the VDR activation status. Although VDR plays an important role in regulating cardiovascular function and VDRAs may be potentially useful for treating CVD, at present VDRAs are not indicated for the treatment of CVD.     

基于肠心轴学说探讨肠道菌群在心血管疾病中的作用

肠道内庞大的菌群之间相互依存、相互制约,协同参与机体生理代谢和营养物质的消化。肠道菌群与心血管健康相关研究已成为十分重要的研究领域,肠道菌群组成的改变、肠道菌群产生的代谢产物和毒素都能引发心血管系统的病变。心血管疾病(cardiovascular disease,CVD)因高发病率和死亡率已成为一个主要的健康问题,CVD的发生、发展中肠道特定菌群的改变已被确定为疾病发生的关键因素。然而,肠道菌群及其代谢产物如何产生及影响CVD的潜在机制仍不清楚。本文就肠道菌群通过肠心轴调节CVD的最新研究进展进行综述,重点总结肠道微生物及其代谢产物与CVD发生发展之间复杂的相互作用,以及肠道菌群失调的改变对心血管事件发生的影响,探讨肠道菌群与CVD发病机制之间的因果联系。     

Smoking Cessation for Patients with Cardiovascular Disease

Tobacco use remains the major preventable cause of early mortality and morbidity in the US and is a major risk factor for cardiovascular disease (CVD). Quitting smoking rapidly reduces the risk of cardiovascular events. In this review, we identify and discuss best approaches to assist smoking cessation among patients with CVD. Establishing office systems that reliably identify smokers to healthcare providers is an essential first step. Once the patient is identified as a smoker, providers should inquire about their willingness to quit and advise them to quit or provide motivation to get ready to make a quit attempt. Behavioral (counseling) and pharmacologic (nicotine replacement and non-nicotine medications) treatments double or triple long-term cessation rates and should be offered in combination to all patients with CVD who use tobacco. More intensive behavioral therapy is more effective and should be delivered when possible. The choice of pharmacotherapy will depend upon the clinical history of the patient and patient preference. Nicotine replacement and sustained release bupropion (bupropion SR) are first-line treatments for smoking cessation. Nicotine patches have been studied extensively in patients with stable CVD and have been shown to be safe. Bupropion SR has relatively few cardiovascular adverse effects and may be especially useful for patients with CVD; its safety is currently being studied. Special consideration is needed for hospitalized patients with acute coronary syndromes (e. g. myocardial infarction and unstable angina). The safety of pharmacotherapy in the acute setting is not yet established. Behavioral interventions, however, are very effective and should be delivered to all hospitalized smokers. Finally, it is important to create a clinical environment that is supportive of treating patients with tobacco dependence. Simple changes in office and hospital routines and procedures (routine screening to identify smokers, prompts to encourage intervention and links to more intensive tobacco dependence treatment programs) will substantially improve the identification, treatment, and outcomes of patients with CVD who use tobacco.     

Biomarkers determining cardiovascular risk in patients with kidney disease

Cardiovascular disease (CVD) remains the leading cause of premature death in patients with chronic kidney disease (CKD). Recent evidence suggests that the interaction of "classic" and "non-classic" cardiovascular risk factors is an important contributor in excessive and accelerated CVD in patients with CKD. Indeed, the imposing cardiovascular morbidity and mortality of CKD patients corresponds to a significant extent in endothelial dysfunction, inflammation, oxidative stress, vascular calcification and volume overload. In addition, the kidney's function decline is independently associated with CVD in patients with chronic kidney disease. Currently, there is a growing interest in the role of new biomarkers that are closely correlated with CVD in CKD population. In current review, we summarize the so far acquired knowledge of the most promising biomarkers and we discuss the major clinical correlations of novel risk factors and new biomarkers of CVD in CKD patients, their predictive value for future cardiovascular events and their use in the treatment monitoring of this population.     

Oxidative stress and cardiovascular disease: antioxidants and unresolved issues

Experimental and clinical studies suggest that oxidative stress contributes to the development and progression of cardiovascular disease. However, clinical trials with classic vitamin antioxidants failed to demonstrate any benefit in cardiovascular outcomes. Recent advances in our understanding of mechanisms involved in free radical generation reinstate that a more comprehensive approach targeting the prevention of reactive oxygen species (ROS) formation early in the disease process may prove beneficial. Experimental studies and reviews in oxidative stress were selected to provide a better understanding of the roles of the reactive species in the initiation and progression of cardiovascular disease (CVD). Clinical studies that evaluated the efficacy of several classes of antioxidants in CVD were included in the second part of this review to discuss future therapeutic guidelines based on currently available evidence. In conclusion, before a potential role for antioxidants in the treatment of CVD is eliminated, more carefully designed studies with classic as well as new antioxidants in well-defined patient populations are warranted to provide a definitive answer.     

Pathophysiological roles of endothelin receptors in cardiovascular diseases

Endothelin (ET)-1 derived from endothelial cells has a much more important role in cardiovascular system regulation than the ET-2 and ET-3 isoforms. Numerous lines of evidence indicate that ET-1 possesses a number of biological activities leading to cardiovascular diseases (CVD) including hypertension and atherosclerosis. Physiological and pathophysiological responses to ET-1 in various tissues are mediated by interactions with ET(A)- and ET(B)-receptor subtypes. Both subtypes on vascular smooth muscle cells mediate vasoconstriction, whereas the ET(B)-receptor subtype on endothelial cells contributes to vasodilatation and ET-1 clearance. Although selective ET(A)- or nonselective ET(A)/ET(B)-receptor antagonisms have been assumed as potential strategies for the treatment of several CVD based on clinical and animal experiments, it remains unclear which antagonisms are suitable for individuals with CVD because upregulation of the nitric oxide system via the ET(B) receptor is responsible for vasoprotective effects such as vasodilatation and anti-cell proliferation. In this review, we have summarized the current understanding regarding the role of ET receptors, especially the ET(B) receptor, in CVD.