Behavioral effects of a calcium channel antagonist: nifedipine

A series of experiments investigated the behavioral effects of a calcium channel antagonist, nifedipine. This antagonist has facilitatory effects on learning and memory as assessed by the active and passive avoidance tests respectively. In the forced swimming test, nifedipine at a dose of 5 mg/kg had an inhibitory effect on immobilization. Finally, nifedipine (2.5 and 5.0 mg/kg) induced an anxiolytic effect in the water consumption test in a novel environment. These findings are discussed with respect to other findings in the same field and to the neurochemical changes known to be induced by calcium channel antagonists.     

Comparison of haemodynamic effects of nifedipine and molsidomine in patients with coronary artery disease

Summary The haemodynamic effects of oral nifedipine 20 mg and molsidomine 4 mg were compared in 24 patients with coronary artery disease.Molsidomine unlike nifedipine caused a significant fall in mean pulmonary artery pressure and left ventricular end-diastolic pressure. Both drugs caused a significant and comparable reduction in systolic and diastolic blood pressure. Although only nifedipine significantly reduced systemic vascular resistance the difference between the drugs was not significant. The heart rate was significantly increased by nifedipine but not by molsidomine. The ejection phase indices were all increased by molsidomine and the increment in the mean normalized systolic ejection rate was significantly greater than that due to nifedipine. The left ventricular end-systolic volume index decreased significantly after molsidomine but not nifedipine.Neither drug significantly affected left ventricular end diastolic volume index, stroke volume index, maximal rate of rise of left ventricular pressure or left ventricular stroke work index.     

Total and free steady-state plasma levels and pharmacokinetics of nifedipine in patients with terminal renal failure

Summary The total and free steady-state plasma levels of nifedipine in patients with renal failure have been compared with those in subjects with normal renal function. Studies were done after administration of nifedipine 10 mg t.d.s. p.o. for 5 days, after i.v. infusion of 4·4 mg, and after a single 10 mg oral dose.The systemic clearance of nifedipine after a single i.v.-dose was higher in subjects with renal insufficiency (854 ml/min) than in those with normal renal function (468 ml/min). After the single oral dose the AUC (6100 ng·min·ml^–1) and maximum plasma concentration (75.0 ng·ml^–1) were lower than in subjects with normal renal function (19300 ng·ml^–1; 122 ng·ml^–1). The plasma protein binding of nifedipine averaged 95.5% in normal subjects and 94.8% in patients with renal failure.Although free and total steady-state plasma levels of nifedipine tended to be somewhat lower than normal in renal failure, the changes in pharmacokinetics and decreased protein binding of nifedipine did not result in a significantly different steady-state plasma level of the drug. The blood pressure response to a given plasma nifedipine level appeared to be enhanced in renal failure.     

CARDIOVASCULAR RESPONSES TO NIFEDIPINE IN ANAESTHETIZED RATS WITH ABNORMAL BLOOD GAS/PH LEVELS

1. Blood pressure and pulse rate responses to intravenously (i.v.) administered nifedipine were studied in chloralose-anaesthetized rats subjected to hypoxaemia, hyperoxaemia, alkalosis, acidosis, hypocarbia with alkalosis, or hypercarbia with acidosis. 2. Ventilation with a gas mixture of 17% O2, 28% O2, or 23% O2 with 5% CO2 at a fixed stroke volume (10 mL/kg) and rate (80 strokes/min) induced hypoxaemia, hyperoxaemia or hypercarbia, respectively. Hypocarbia was induced by ventilation with 17% O2 at 160 strokes/min. Acidosis or alkalosis was produced by intravenous infusion of 1 mol/L HCl or 1 mol/L NaHCO3, respectively, in animals ventilated with room air. 3. There were significant decreases in blood pressure and pulse rate during acidosis, and increases in pulse rate during alkalosis and hypercarbia. No marked changes in these parameters were observed under the other experimental conditions. 4. The control animals showed a dose-dependent decrease in blood pressure without marked changes in pulse rate in response to nifedipine injection. 5. Significant reductions in the hypotensive effect of nifedipine were observed in rats subjected to alkalosis, acidosis, or hypercarbia. A similar tendency was also found during hypocarbia while the responses to nifedipine during hypoxaemia and hyperoxaemia were statistically the same as those in the controls. 6. It is concluded that alterations of blood pH reduce the hypotensive effect of nifedipine, and we suggest that blood pH changes probably play a more important role than PO2 or PCO2 abnormalities in altering the cardiovascular responses to nifedipine in hypoventilated or hyperventilated rats.     

硝苯毗啶及山莨菪碱对大鼠血小板膜流动性及血小板聚集功能的影响

硝苯吡啶与山莨菪碱分别可使大鼠血小板膜微粘度最大增加38.3％及37.1％.并使大鼠血小板5min最大聚集率降低40.5％及42.0％(P值皆小于0.001)。药物效应随其浓度增加而增强,当药物浓度达最大药物效应时,再增加浓度反而使其药物效应减弱。两种药物的血小板膜作用曲线及其抑制血小板聚集作用曲线基本相似。     

国产硝苯地平控释片治疗高血压并左室肥厚的临床研究

目的：评价国产控释剂型的硝苯地平（欣然）治疗高血压并左心室肥厚的临床疗效。方法：60例高血压病并左室肥厚患患者随机分为两组，欣然组（国产硝苯地平控释片）和拜新同（德国产硝苯地平控释片）组各30例，30mg／d口服，治疗3个月，观察降压疗效和左室肥厚的变化，结果：（1）欣然组降总有效率90％，拜新同组总有效率96．6％，两组疗效比较差异无显著性，P＞0．05。（2）两组治疗后左室内径，舒张期室间隔厚度和左室壁厚度均缩小，左室重量减少，左室射血分数提高，与治疗前比较均有显著性差异（P＜0．05），两组各项指标变化差值比较无显著差异（P＞0．05），结论：欣然能有效治疗高血压，并能逆转左心室肥厚。     

观察硝苯地平缓释片联合厄贝沙坦片治疗高血压合并糖尿病的疗效

目的 探讨硝苯地平缓释片(圣通平)与厄贝沙坦片联合治疗对原发性高血压(以下简称高血压)合并2型糖尿病(以下简称糖尿病)患者的应用效果。方法 回顾性分析2017年10月至2018年9月在某社区服务中心治疗的112例高血压合并糖尿病患者的临床资料,依据用药方案的不同,分为观察组(硝苯地平缓释片+厄贝沙坦片,56例)与对照组(硝苯地平缓释片,56例),比较2组降压效果与肾功能指标[尿素氮(Blood urea nitrogen,BUN)、尿白蛋白排泄率(Urinary albumin excretion ratio,UAER)、尿微量白蛋白(Microalbuminuria,mAlb)]。结果 治疗前,两组血压、BUN、UAER及mAlb水平对比,差异无统计学意义(P>0.05);治疗3个月后,观察组血压、UAER与mAlb水平均明显低于对照组,差异有统计学意义(P<0.05)。结论 高血压合并糖尿病患者采用硝苯地平缓释片与厄贝沙坦片联合治疗后,可有效控制血压水平,利于减轻肾功能损伤。     

硝苯地平对野百合碱所致大鼠肺动脉高压的影响

目的探讨硝苯地平 (Nif)对野百合碱 (MCT)诱发慢性炎性肺动脉高压的防治作用。方法 3 3只雄性Wistar大鼠随机分为正常对照组、肺动脉高压模型组、Nif治疗组 ,每组 11只。予MCT (5 0mg/kg)制做大鼠肺动脉高压模型后 ,分别给Nif组及模型组大鼠连续灌胃Nif(2 0mg/kg·d)和等量生理盐水 2 1d。采用改良右心导管术测定肺血流动力学参数 ;处死大鼠后 ,称量肺湿重 (wW )、右心室自由壁 (RV)和左心室加室间隔 (LV S)重 ,计算右心肥厚指数 (RV/LV S)。结果Nif能明显降低肺动脉高压模型大鼠的平均肺动脉压及RV/LV S(P <0 0 1) ,但对wW无明显影响 (P >0 0 5 )。结论长期使用Nif能有效防治MCT所致肺动脉高压 ,改善心功能。     

卡托普利与缓释硝苯地平治疗对高血压病患者运动血压的影响

目的:探讨原发性高血压(EH)经治疗血压稳定下降后,运动后血压反应是否恢复正常,以及观察卡托普利与缓释硝苯地平治疗有无差异。方法:观察正常成人22例,44例EH患者随机分为卡托普利和硝苯地平治疗2组。卡托普利始用12.5mg,2次/d,缓释硝苯地平始用10mg,2次/d,治疗2周,血压未降至正常者,分别加至25mg,2次/d或20mg,2次/d;观察3个月。观察结束前1周测定运动前、运动后即刻、5、10、15min血压,计血压恢复至运动前水平的时间(血压恢复时间)。结果:正常组运动后SBP和DBP升高幅度分别为(12.6±3.3)mmHg和(-0.1±2.6)mmHg,血压恢复时间为(5.9±2.0)min;高血压治疗2组虽然血压得到满意控制,但上述参数仍明显增加;但卡托普利组运动后SBP/DBP升幅明显小于硝苯地平组[(14.9±3.2)mmHg/(8.8±3.3)mmHg比(18.9±7.7)mmHg/(11.6±4.5mm)Hg,P均<0.05)];血压恢复时间更短[(9.8±4.6)min比(13.3±5.3)min,P<0.05)]。结论:高血压病患者即使血压得到有效控制,运动血压增幅和血压恢复时间仍明显大于正常血压者。与缓释硝苯地平比较,卡托普利治疗运动血压增幅更小,血压恢复时间更短。     

硝苯地平缓释片联合依那普利治疗冠心病合并高血压患者的疗效及其对NO、CRP、HCY的影响

目的探讨硝苯地平缓释片联合依那普利治疗冠心病合并高血压患者的疗效及其对一氧化氮(NO)、C-反应蛋白(CRP)、同型半胱氨酸(HCY)的影响。方法将116例冠心病合并高血压患者随机分成观察组和对照组各68例。对照组给予口服硝苯地平缓释片;观察组给予硝苯地平缓释片联合依那普。比较2组患者治疗后的临床疗效和NO、CRP、HCY水平的变化,以及治疗过程中的不良反应发生情况。结果治疗后观察组患者的总有效率显著高于对照组(P0.05);2组患者的NO水平在治疗后均显著升高(P0.05),CRP和HCY水平均显著下降(P0.05),且观察组NO、CRP和HCY水平显著优于对照组(P0.05)。2组患者不良反应发生率无显著差异(P0.05)。结论硝苯地平缓释片联合依那普利治疗冠心病合并高血压疗效显著。