钙增敏剂左西孟旦的研究进展

新型钙增敏剂左西孟旦(LS)通过增加细胞收缩蛋白对Ca2+的敏感性及K+通道的开放而兼有强心和扩血管作用.LS强心时不增加心肌耗氧,因此适用于心力衰竭、心肌缺血及心源性休克患者的强心治疗.最新研究表明,LS具有减轻炎症反应、抑制细胞凋亡等作用,提示LS在感染性休克强心治疗可能有优势.本文主要就LS新近的研究进展作一综述.     

新型钙增敏剂左西孟旦在失代偿性心力衰竭中的应用及疗效评价

目的评价左西孟旦注射液在治疗充血性心力衰竭患者中的临床疗效及安全性。方法选取重症充血性心力衰竭患者47例,随机分为观察组和对照组。对照组患者给予常规治疗:除了一般治疗外,给予洋地黄强心、利尿剂、血管扩张药、β受体阻滞剂等治疗。观察组在对照组用药基础上,静脉应用左西孟旦注射液治疗,用药前后检查超声心动图评估心功能,监测肝、肾功能,心率,血压变化、呼吸困难程度及血生化指标的变化。结果治疗后两组左室射血分数明显加强(P<0.05),临床症状及体征均有不同程度的改善,观察组总有效率与对照组比较,差异有统计学意义(P<0.05)。结论左西孟旦可使充血性心力衰竭患者射血分数提高,呼吸困难程度下降,全身状况改善。可有效地减轻心脏负荷,改善心脏收缩功能,而且患者的耐受性好,较为安全。     

新型钙增敏剂的研究进展

钙增敏剂能够避免传统强心药的某些缺点,成为一类新的治疗充血性心力衰竭(CHF)的药物,具有广泛的应用前景。本文对钙增敏剂的分类、作用机制、临床试验情况及其与PDE-Ⅲ抑制活性之闻的关系等方面进行综述。     

新型钙增敏剂的研究进展

钙增敏剂是一类新的强心药物,该类药物通过增加心肌收缩蛋白对Ca2+的敏感性来发挥强心作用,克服了传统强心药增加心肌耗氧量和引起细胞内钙超载等缺点,在治疗心衰、休克及心脏保护方面有良好的发展前景。文中综述了该类药物的分类、已上市药物及正在进行临床研究药物近年的研究进展。     

新型钙增敏剂的研究进展

钙增敏剂是在研究治疗充血性心力衰竭的新型强心药时发现的一类作用机制完全不同于传统强心剂的强心药物。它们主要通过增强心肌收缩系统对Ca^2＋的敏感性来发挥强心作用。近年来发现，钙增敏剂不仅在治疗心衰方面有着较好的应用前景，而且还有良好的抗休克以及调节外周血管反应性、改善器官组织血流量等作用。     

盐酸椒苯酮胺稳定性考察

目的 考察盐酸椒苯酮胺的稳定性.方法 依据2010年版<中国药典(二部)>附录药物稳定性试验指导原则的有关技术要求,进行盐酸椒苯酮胺稳定性试验,包括影响因素试验、加速试验、长期试验.结果 2年考察结果显示,3批样品的外观性状、熔点、溶液颜色和澄清度、pH、干燥失重、含量均无显著变化,单个及总有关物质含量有所增加.结论 盐酸椒苯酮以塑料瓶包装,在常温阴凉处保存,有效期暂定2年.     

注射用盐酸椒苯酮胺配伍稳定性研究

目的 考察注射用盐酸椒苯酮胺在不同制剂中的配伍稳定性.方法 采用高效液相色谱(HPLC)法测定注射用盐酸椒苯酮胺在10％葡萄糖注射液(pH=4.4)、5％葡萄糖注射液(pH=4.8)、5％葡萄糖氯化钠注射液(pH=3.9)和0.9％氯化钠注射液(pH=5.1)中的溶液澄清度、颜色、澄明度,并测定2,6,12,24h时含量变化.结果 本品在酸性液体中稳定,加入10％葡萄糖、5％葡萄糖或5％葡萄糖氯化钠注射液中,24 h内稳定性良好.结论 本品可加入葡萄糖注射液或5％葡萄糖氯化钠注射液中使用,不宜加入0.9％氯化钠注射液中使用.     

Pharmacokinetics of levosimendan and its circulating metabolites in patients with heart failure after an extended continuous infusion of levosimendan

AIMS: The purpose of the study was to characterize the pharmacokinetics of levosimendan and its metabolites OR-1855 and OR-1896 in patients with congestive heart failure. METHODS: Levosimendan was administered as a continuous intravenous infusion for 7 days. Twelve subjects received the drug at an infusion rate of 0.05 micro g kg(-1) min(-1) and 12 at a rate 0.1 micro g kg(-1) min(-1). RESULTS: Steady state concentrations of levosimendan were achieved within 4 h. Peak concentrations of the metabolites occurred after termination of the infusion. The mean (+/- SD) half-life of the active metabolite OR-1896 was 81 +/- 37 h after the lower dose and 81 +/- 28 h after the higher dose (P = 0.992, 95% confidence interval on the difference -27.5, 27.7). CONCLUSIONS: The metabolites of levosimendan, OR-1855 and OR-1896, were formed and eliminated slowly, their peak concentrations occurring after termination of the 7-day infusion of the drug.     

左西孟旦在临床麻醉和重症监护病房中的应用及前景

左西孟旦是一种新型钙增敏剂,在增强心肌收缩力的同时不增加细胞内钙负荷,能激活ATP敏感性钾通道(K_(ATP)通道),具有抗心力衰竭、抗心肌顿抑、降低周围血管阻力、舒张冠状动脉及肺血管等作用。本文综述左西孟旦在临床麻醉和重症监护病房(ICU)中的应用。     

Section Review: Cardiovascular & Renal: Calcium sensitisers and heart failure

To date, the use of positive inotropic agents for the treatment of heart failure has not been a success. Not only have these drugs had little documentable beneficial effect on survival, but in some instances, most notably with the phosphodiesterase inhibitors, they have-caused an unacceptable increase in early mortality due to arrhythmias [1]. This has led to a body of opinion in some quarters that positive inotropic therapy for heart failure is a doomed approach and that all efforts should be concentrated on preventing or reversing atheroma, enhancing blood flow to the myocardium and dealing with the effects of secondary compensatory mechanisms. Although everyone agrees that prevention is better than cure, it seems inevitable that there will always be substantial numbers of patients with heart failure of various degrees of severity. Thus, it is important to be very sure of the facts before abandoning any hope of pharmacological contractile support for these patients. This article briefly reviews current evidence on the potential utility of calcium sensitisers.     

左西孟旦注射液在中国健康人体的药代动力学

目的研究左西孟旦注射液在中国健康人体的药代动力学。方法 30名健康男性受试者,采用随机、开放、单剂量试验设计,分别单次静脉注射左西孟旦注射液1.0,2.0,3.0 mg。用HPLC法测定血药浓度;用WinNonlin软件计算药代动力学参数。结果 3个剂量左西孟旦的主要药代动力学参数:Cmax分别为(109.24±14.52),(201.38±38.94)和(317.65±45.75)ng.mL-1;Tmax分别为(11.5±2.4),(11.5±3.4)和(11.9±2.6)min;t1/2分别为(0.68±0.10),(0.60±0.08)和(0.80±0.08)h;AUC0-t分别为(81.38±12.64),(143.13±29.63)和(289.86±48.57)μg.h.L-1。结论 1～3 mg给药剂量范围内,左西孟旦均具有线性动力学特征。     

Haemodynamic interactions of a new calcium sensitizing drug levosimendan and captopril

Objective: Levosimendan in a new inodilator drug that sensitises troponin C in heart muscle cells to calcium, thus improving contractility. In previous studies, a single 2 mg intravenous dose of levosimendan increased cardiac output (CO) in healthy volunteers by about 40% and decreased pulmonary capillary wedge pressure in heart failure patients by 40–50%.The aim of the present, double-blind study was to evaluate the safety of concomitant use of levosimendan and an ACE-inhibiting drug. Methods: The haemodynamic effects of levosimendan, given with or without captopril, were evaluated by using 2-dimensional echocardiography, repeated blood pressure measurements and by ambulatory ECG recordings. Twenty-four male patients with stable NYHA II-III heart failure (EF<40%) after a previous myocardial infarct were given, in randomised order, a single IV infusion of levosimendan or placebo. The infusions were repeated after 2 weeks treatment with upto 50 mg b.i.d. of captopril. Twelve patients received levosimendan 1 mg and twelve received 2 mg. Results: Mean CO was increased from 6.0 to 6.81·min^–1 in patients receiving 1 mg levosimendan compared to placebo, but only from 6.3 to 6.51·min^–1 in patients receiving 2 mg. The increase in CO was statistically significant when all levosimendan patients were compared to placebo. Heart rate did not change after either dose. Mean stroke volume increased significantly after 1 mg but not after 2 mg of levosimendan. The addition of captopril did not change the effects of levosimendan. No additional decrease in systolic or diastolic blood pressure was observed when levosimendan and captopril were given concomitantly. Conclusion: It seems that concomitant treatment with captopril does not change the haemodynamic effects of levosimendan. No adverse haemodynamic interactions were seen.     

左西孟旦对右心室衰竭大鼠右心功能、心肌能量代谢和心肌代谢的影响

目的：探究左西孟旦对右心室（RV）肥厚和衰竭者右心功能,心肌耗氧量,心肌能量代谢（MEE）和心肌代谢的影响。方法：右心室衰竭（right ventricular heart-failure,RVF）大鼠肥大和衰竭是由肺部躯干条带诱导的。将大鼠随机（数字表法）分配到安慰剂组（n=16）或左西孟旦组（3 mg·kg^-1·d^-1）（n=13）进行7周干预。通过超声心动图,¹¹C-乙酸正电子发射断层扫描（PET）,¹⁸F-FDG PET和有创压力测量来评估RV MEE和RV代谢。结果：左西孟旦在不影响RV心肌耗氧量的情况下,通过增加右室外径[（0.62±0.06） vs.（0.30±0.03） mm,P<0.001],可改善RV MEE[（26±3）% vs. （14±1）%,P<0.01]。RV MEE的改善与RV心肌葡萄糖摄取的变化无关[（1.3±0.1） vs. （1.0±0.1） μmol·g^-1·min^-1,P=0.44]。在大鼠的肥大和衰竭RV中,左西孟旦改善RV功能而不增加心肌耗氧量,从而改善MEE。结论：左西孟旦对右心衰竭具有潜在的治疗价值,可扩展左西孟旦的临床应用范围。     

强心甾类固醇选择性抗肿瘤机制与相关抗肿瘤药的研究进展

强心甾类固醇（CTS）是一类能与真核细胞胞膜钠钾ATP酶特异性结合的化学物质。近年来研究发现CTS具有抗肿瘤活性,CTS制剂能选择性抑制肿瘤细胞增殖或促进肿瘤细胞凋亡。目前已证实CTS能与钠钾ATP酶结合激活一系列信号通路,导致肿瘤细胞选择性凋亡,而正常细胞不受影响。本文就CTS抗肿瘤机制的研究进展以及新一代具有更强抗瘤活性的CTS衍生物特点作简略综述。     

Alcohol and the brain: recent advances in biomedical research

Considerable progress has been made in our understanding of the cellular mechanisms of action of alcohol on the brain, particularly in relation to tolerance and dependence. Tolerance is associated with changes in the composition of the gamma-aminobutyric acid-benzodiazepine receptor, making it less sensitive to alcohol. An increased density of excitatory glutamate receptors may underlie certain withdrawal manifestations. Other neuroadaptive mechanisms include an increase in presynaptic calcium influx on depolarization and effects on adenylate cyclase. Alcohol also influences the expression of a proto-oncogene which plays an important role in neural development. Further advances in neurobiology offer the prospect of elucidating the mechanisms of tolerance and brain damage.     

重庆市临床研究协调员/临床监查员的工作流动性现状和对策

目的 了解重庆市临床研究协调员(CRC)、临床监查员(CRA)的工作流动性现状,探讨提高CRC、CRA工作稳定性的可行方法.方法 以问卷形式对重庆市22家药物临床试验机构的200名CRC和CRA进行工作流动性情况调查,内容涉及人员基本情况、工作流动性情况、流动原因等方面.结果与结论 回收有效问卷178份,有效回收率89...     

Peptide-based drug discovery: Current status and recent advances

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