International nifedipine trial on antiatherosclerotic therapy (intact)

Summary A number of animal studies revealed an inhibition or retardation of the progression of atherosclerosis by calcium-antagonists. Encouraged by these studies, a multicenter trial on the progression of coronary artery disease (CAD) in man was initiated testing the antisclerotic effect of nifedipine against placebo in 426 patients with mild to moderate coronary disease over 3 years. All patients underwent coronary angiography before entering the trial and will be restudied after 3 years; changes of the coronary artery lumen size are quantitatively assessed by a computer-assisted system (CAAS). INTACT (International Trial on Antiatherosclerotic Coronary Therapy) is therefore the first randomized prospective study on the progression of CAD based on a quantitated anigraphic control of the coronary system.This report presents the design of this still-ongoing study as well as inclusion and exclusion criteria. The quantitative evaluation of the coronary angiograms and the mode of compliance test are described in detail. A number of baseline data as well as the preliminary results of the quantitative evaluation of the first coronary angiograms are presented.Beside the results on the effect of the calcium-antagonist nifedipine on the progression of CAD, INTACT might also supply information on the antiatherosclerotic potency of other drugs administered additionally (beta-blockers and nitrates) and of HDL-cholesterol.     

Comparison of acute haemodynamic effects of nifedipine and isosorbide dinitrate in patients with heart failure following acute myocardial infarction

The acute haemodynamic effects of nifedipine (10 mg sublingually) and isosorbide dinitrate (5 mg sublingually) were compared in 13 patients with heart failure due to acute myocardial infarction. Nifedipine induced a significant reduction in systolic (from 122 ± 5 to 107 ± 3 mm Hg: mean ± SEM; P < 0.002) and diastolic blood pressure (from 85 ± 3 to 75 ± 2 mm Hg; P < 0.01). Heart rate did not change significantly, nor did mean right atrial pressure. The mean pulmonary arterial pressure was lowered from 31 ± 2 to 27 ± 2 mm Hg (P < 0.005). The left ventricular filling pressure decreased from 24 ± 1 to 19 ± 1 mm Hg (P < 0.0001). A significant increase in cardiac index (from 2.33 ± 0.13 to 2.69 ± 0.15 l/min per m²; P < 0.001) and in stroke volume index (from 24 ± 2 to 28 ± 2 ml/beats per m²; P < 0.005) was registered. Systemic vascular resistance fell from 1742 ± 145 to 1308 ± 85 dynes/sec per cm⁻⁵ (P < 0.00005). After isosorbide dinitrate was administered a significant reduction in mean right atrial pressure (from 9.5 ± 1.6 to 5.1 ± 1.2 mm Hg; P < 0.0001), in mean pulmonary arterial pressure (from 32 ± 1 to 23 ± 1 mm Hg; P < 0.00001) and in left ventricular filling pressure (from 23 ± 1 to 16 ± 1 mm Hg; P < 0.0001) was seen. No significant change in systolic and diastolic blood pressure, heart rate, cardiac index, stroke volume index and systemic vascular resistance was registered. No side-effects were seen after nifedipine and isosorbide dinitrate were administered.     

药物性牙龈肥大发病机制的研究进展

药物性牙龈肥大(DIGO)主要由长期服用苯妥英钠、环孢素A、硝苯地平引起,不仅影响牙面的清洁与美观和牙齿正常生理功能,而且可能造成患者心理上的障碍。然而,DIGO发病机制复杂,无法明确,导致治疗较为棘手。许多学者对其进行了多方面的研究,提出许多观点与假设,包括胶原生成与降解失衡机制、炎症等。该文从分子机制与药物具体机制两方面总结了近几年对DIGO发病的研究,并对DIGO未来的研究方向进行探讨,希望能够对DIGO的预防与临床治疗有所帮助。     

Effect of a New Vasodilator,Pinacidil (P 1134), on Potassium,Noradrenaline and Serotonin Induced Contractions in Rabbit Vascular Tissues

Abstract: Ring preparations of rabbit aorta were contracted by potassium (127 mM). Pinacidil (P 1134), a new vasodilator (2.3×10⁻⁵ M), the calcium antagonists verapamil (3.4×10⁻⁷ M), nifedipine (3.4×10⁻⁹ M) and hydralazine (1.9×10⁴ M) relaxed the preparation by 50%. 50% relaxation of noradrenaline-contracted tissues was obtained with pinacidil, 6.8×10⁻⁵ M, verapamil, 2.4×10⁻⁴ M and hydralazine, 1.9×10⁻³ M. At 2×10⁻⁷ M concentration nifedipine was almost inactive. In ring preparations of rabbit aorta exposed to calcium-free medium and then depolarized with potassium (127 mM), pinacidil, 5×10⁻⁵ M and nifedipine, 10⁻⁸ M significantly inhibited the contractions by cumulative addition of calcium. Hydralazine, 10⁻³ M had no effect. Noradrenaline-induced contractions in calcium-free medium or in presence of increasing amounts of calcium were significantly inhibited by nifedipine, 10⁻⁸ M and hydralazine, 10⁻³ M. Pinacidil, 10⁻⁴ M had no effect. Pinacidil, 1.3×10⁻⁵ M and verapamil, 2.0×10⁻⁵ M inhibited by 50% the serotonin-induced increase of perfusion pressure of isolated rabbit ear artery. The noradrenaline effect in this preparation were 50% inhibited by pinacidil, 2.4×10⁻⁴ M and by verapamil, 8.8×10⁻⁵ M. Hydralazine, 10⁻³ M exerted minor inhibitory effect. It is suggested that interference with calcium influx contributes to the vasodilator activity of pinacidil.     

硝苯地平联合拉贝洛尔对妊高征患者血管功能、凝血功能及妊娠结局的影响

目的 观察硝苯地平联合拉贝洛尔对妊娠高血压综合征(简称妊高征)患者血管功能、凝血功能及妊娠结局的影响.方法 随机选择2019年1月至2020年12月来我院诊治的150例妊高征患者为研究对象,按随机数字表法将其分为对照组和观察组,各75例.对照组采用硝苯地平治疗,观察组采用硝苯地平联合拉贝洛尔治疗.比较两组的血压控制效果...     

硝苯地平对去负荷比目鱼肌肌球蛋白重链(MHC)异构体转化的影响

目的观测L型钙离子通道抑制剂硝苯地平对尾部悬吊大鼠比目鱼肌重量,以及肌球蛋白重链(MHC)表达水平的影响。方法经饮水每天给予大鼠10mg／kg体重的硝苯地平1与2周。称量比目鱼肌(SOL)与趾长伸肌(EDL)的湿重,用低温SDS-聚丙烯酰胺凝胶电泳观测MHC异构体蛋白表达,并用RT—PCR方法观测MHCmRNA的表达。结果与正常对照组相比,给予硝苯地平处理1与2周的同步对照组大鼠SOL的相对重量未见明显改变;而尾部悬吊1周与2周大鼠SOL的相对重量则分别降低了39．5％和51．7％。经硝苯地平处理的1与2周悬吊大鼠的SOL相对重量较其对照组分别降低了36．6％与52．0％,但与同步悬吊组相比,无明显差异。各组EDL相对重量均未见明显改变。正常对照组与经硝苯地平处理的对照组可检测到MHCⅠ、Ⅱa mRNA与蛋白的表达,悬吊组与经硝苯地平处理的悬吊组可检测到MHCⅠ、Ⅱa、Ⅱb与Ⅱx mRNA以及MHCⅠ与Ⅱa蛋白的表达。在对照组与悬吊组,硝苯地平对Ⅱ型MHC mRNA表达均产生抑制作用,并降低MHC Ⅱa蛋白表达。结论硝苯地平不能防止去负荷引起的SOL萎缩,但在转录水平抑制萎缩SOL的MHC异构体由慢型向快型转化。     

缬沙坦联合硝苯地平缓释片治疗原发性高血压的临床疗效观察

目的：探讨缬沙坦联合硝苯地平缓释片治疗原发性高血压的临床疗效。方法：选择我院内科门诊治疗的86例原发性高血压患者,随机分为缬沙坦联合硝苯地平缓释片治疗组（A组,n=43）和单用缬沙坦对照组（B组,n=43）。对两组患者治疗4周后的有效性和安全性进行比较。结果：两组血压均有下降,A组下降明显,治疗总有效率95．3％,B组总有效率76．7％,两组比较差异有统计学意义（P〈0．05）。结论：缬沙坦联合硝苯地平缓释片治疗原发性高血压降压有效率优于单用缬沙坦。     

多剂量口服硝苯地平缓释片的药动学及生物等效性

目的：研究多剂量口服硝苯地平缓释片在人体内的药动学特点和国产硝苯地平缓释片的生物等效性.方法：健康志愿受试者20名,口服硝苯地平试验品和参比品20mg,用标准二阶段交叉设计自身对照试验方法,采用液相色谱串联质谱方法（LC-MS/MS）测定服药后不同时刻的血药浓度,计算主要药动学参数,并采用方差分析和双单侧t检验（1-2a）90%置信区间进行生物等效性评价.结果：受试者分别口服受试品和参比品后,其主要药动学参数Tmax,Cmax,T1/2和AUCss分别为：（4.10±1.07）,（4.55±1.23）h;（52.64±15.80）,（51.54±12.87）μg/L;（8.44±1.69）,（8.33±2.27）h;（352.96±85.12）,（367.96±71.28）ng/（h·mL）;受试品的相对生物利用度为（96.2±17.3）%.结论：硝苯地平缓释片和硝苯地平缓释片（1）制剂具有生物等效性.     

特拉唑嗪在治疗老年顽固性高血压中的疗效观察

目的探讨特拉唑嗪在治疗老年原发性顽固性高血压的临床疗效。方法将我院收治的80例顽固性高血压患者随机分成两组,均为原发性高血压。对照组36例使用拜新同及安博诺治疗,治疗组44例在对照组的基础上加用特拉唑嗪治疗,两组疗程均为6周。结果治疗组的总有效率明显高于对照组,两组相比较差异有统计学意义（P〈0.05）;两组治疗后的收缩压与舒张压均较治疗前有明显下降,治疗前后差异具有统计学意义（P〈0.05）,治疗组的降压效果明显优于对照组。结论盐酸特拉唑嗪联合多种降压药治疗老年顽固性高血压效果良好,副作用少,值得临床推广。     

硝苯吡啶控释片降压效果观察

应用硝苯吡啶控释片及其普通片剂对４３例高血压患者进行为期４周的治疗，对比结果显示：硝苯吡啶控释片每日口服一次剂量３０ｍｇ，降压平稳，持续２４ｈ，降压总有效率为９０９％，且不增加心率，不良反应轻微。