三种治疗高血压药物的成本-效果分析

目的对3种治疗高血压药物进行经济学评价。方法运用成本-效果分析法对氨氯地平、非洛地平、缓释硝本地平的疗效及成本进行比较。结果3组成本-效果比分别为1.14、0.81、0.78。结论缓释硝本地平为最佳方案。     

结缔组织生长因子与原发性高血压模型大鼠心肌纤维化的关系及药物干预研究

目的 评价结缔组织生长因子（CTGF)与原发性高血压模型大鼠（SHR）心肌纤维化的关系,以及CTGF作为抗心肌纤维化靶点的敏感性。方法 将32只14周龄雄性SHR随机分为SHR对照组、卡托普利组、硝苯地平组和螺内酯组各8只,SHR对照组不给予任何药物,其他3组分别灌胃给予卡托普利100 mg•kg-1•d-1、硝苯地平30 mg•kg-1•d-1 、螺内酯30 mg•kg-1•d-1,共12周。同时设8只同龄雄性SD大鼠为正常对照组。免疫组化法和RT-PCR法检测各组大鼠转化生长因子β1（TGF-β1）和CTGF表达情况,MASSON染色分析测量胶原容积分数（CVF）,碱水解法测定羟脯氨酸(Hypro)含量。结果 SHR对照组左室重量指数（LVI）、CVF、Hypro、CTGF、TGF-β1表达均明显高于正常对照组（均P＜0.01）;与SHR对照组比较,卡托普利组和螺内酯组LVI、CVF、Hypro、CTGF、TGF-β1表达显著降低（均P＜0.05）;CTGF、TGF-β1、CVF、Hypro和LVI呈高度正相关（P＜0.01）。结论 CTGF与SHR心肌纤维化关系密切,卡托普利、螺内酯能抑制其表达,CTGF可作为新的抗心肌纤维化靶点。     

Long-term effects of nifedipine on carbohydrate and lipid metabolism in hypertensive hemodialyzed patients

Summary To evaluate long-term effects of nifedipine on carbohydrate and lipid metabolism, 15 hypertensive patients undergoing regular hemodialysis treatment were investigated before nifedipine therapy, after 3 and 9 weeks, and 2 weeks after stopping nifedipine therapy. Three weeks following the administration of nifedipine, both glucose and insulin concentrations decreased significantly from 102.1±2.6 to 94.9±2.2 mg/dl and from 19.9±2.9 to 13.9±1.7 µU/ml and also remained significantly lower after 9 weeks of nifedipine therapy. This effect was paralleled by a fall of noradrenaline and dopamine. Glucagon levels remained constant. Glucose tolerance tests performed during nifedipine medication and 2 weeks after stopping of nifedipine therapy did not differ significantly. An increase of pyruvate, citric acid cycle intermediates, and ketone bodies — but not of lactate — was registered during nifedipine medication. The observed effects were not completely abolished after the 2-week placebo phase. Our data indicate that nifedipine lowers serum glucose values despite decreased insulin and constant glucagon levels in hypertensive hemodialyzed patients. Considering additionally the behavior of catecholamines and organic acids, the effects could be explained by the improvement of peripheral glucose utilization.Abbreviations BUN Blood urea nitrogen - PCA Perchloric acid - RDT Regular hemodialysis treatment     

Pharmakokinetik und kardiale Wirksamkeit von β-Acetyldigoxin und Digitoxin unter einer Kombinationstherapie mit Nifedipin

Summary The effect of nifedipine (N) on the pharmacokinetics and pharmacodynamics of -acetyldigoxin (AD;n=11) and digitoxin (DGT;n=10) was studied in 21 patients with cardiac insufficiency stage II–III NYHA. Glycoside plasma concentration and renal excretion as well as electrocardiogram heart rate, atrioventricular transconduction time (PQ), duration of electrical systole corrected for heart rate (QT_c), mean amplitude of T waves in leads V₂ to V₆ (T_V2–6) and systolic time intervals total electromechanical systole index (QS_2I), left ventricular ejection time index (LVET_I), pre-ejection period index (PEP_I), PEP/LVET-ratio were recorded repeatedly before and during coadministration of 40–60 mg/day N. Plasma AD concentrations were 0.64±0.22 ng/ml (mean±SD) before and 0.61±0.21 ng/ml during co-administration of N over 10–14 days, plasma DGT concentrations 13.9±4.1 ng/ml before and 13.7±4.5 ng/ml during co-administration of N over 4–6 weeks. Daily glycoside excretion was not affected by treatment with N. Heart rate and PQ-interval were not significantly changed during co-administration of N whereas T-wave flattening was intensified and QT-duration was lengthened. Concomitant treatment of AD and N led to an increase of PEP_I and PEP/LVET compared to AD alone in ten patients whereas the systolic time intervals after concomitant treatment of DGT and N in most patients did not differ from those after DGT alone. From our findings we conclude that N had no clinically significant effect on pharmacokinetics and pharmacodynamics of AD or DGT.

     

Inhibition of angiotensin II and platelet-derived growth factor-induced vascular smooth muscle cell proliferation by calcium entry blockers

Summary Structural changes within the blood vessel wall such as hyperplasia and hypertrophy of vascular smooth muscle cells are important factors in the pathogenesis of hypertension. Humoral growth factors such as angiotensin II (AII) and platelet-derived growth factor BB (PDGF-BB) may participate in the remodelling of the blood vessel wall. Whether and by which mechanisms antihypertensive treatment is capable of influencing the structural blood vessel alterations to date remains unclear. In the present study, the effect of nifedipine and diltiazem on AII- and PDGF-BB-induced vascular smooth muscle cell proliferation was examined. Nifedipine and diltiazem at a concentration of 10 M did not affect baseline DNA synthesis in isolated vascular smooth muscle cells in culture. AII (final concentration 100 nM) and PDGF-BB (50 ng/ml) stimulated DNA synthesis by approximately 9.0- and 4.6-fold, respectively. Both AII- and PDGF-BB-induced DNA synthesis was significantly blunted by diltiazem and nifedipine in a concentration of 10 M, while no significant influence was seen with concentrations from 10 nM up to 1 M. In contrast, no significant influence of these drugs could be observed on fetal calf serum 5%-induced DNA synthesis. The findings indicate that calcium antagonists possess antimitogenic potential and that they may thus contribute to the regression of structural changes of the blood vessels associated with hypertension.Abbreviations PDGF-BB platelet-derived growth factor BB - AII angiotensin II - FCS fetal calf serum - VSMC vascular smooth muscle cells - ACE angiotensin I converting enzyme This work was supported by HEXAL-PHARMA, Holzkirchen, Federal Republic of Germany     

Comparison of nitroglycerin with nifedipine in patients with hypertensive crisis or severe hypertension

Summary To determine whether nitroglycerin is as effective as nifedipine in lowering the blood pressure in severe hypertension and hypertensive crisis, two goups of 20 patients received in random sequence either 1.2 mg nitroglycerin sublingually or a 10-mg nifedipine capsule, which was chewed and swallowed. The blood pressure fell after 5 min in the nitroglycerin group from 211/122 mmHg to 171/95 mmHG and after nifedipine from 210/118 to 185/102 mmHg. The greater effect of nitroglycerine may result from faster absorption through the oral mucosa than through the small intestinal mucosa where nifedipine is primarily absorbed. After 15–20 min a satisfactory reduction in blood pressure was reached in both groups: 157/91 and 158/92 mmHg, respectively. After 30 min the heart rate in the nitroglycerin group had decreased from 83 to 80/min, but in the nifedipine group it had increased from 84 to 90/min. The reduction in blood pressure persisted up to 6 h. No significant differences in side effects were determined. Since a hypertensive crisis is usually accompanied by left ventricular failure, pulmonary edema, angina pectoris, or infarction, nitroglycerin has been definitively shown positively to influence these conditions, and preference should be given to nitroglycerin in the treatment of hypertensive crises.     

硝苯吡啶治疗原发性高血压病的甲襞微循环监测

对５０例高血压病组用硝苯吡啶不同剂量（５、１０、２０ｍｇ）及２５例正常血压组，用硝苯吡啶１０ｍｇ药前及药后１、２、３、４ｈ同步进行甲襞微血管管径输入枝、血压、心率、温度４项参数同步观察。认为甲襞输入枝管径、血压、心率无论是正常血压组或是高血压病组，用药后均有显著差异，而输入枝管径的恢复时间随高血压分期而有所不同。     

硝苯地平(硝苯吡啶)对原发性高血压患者血浆心钠素、淋巴细胞内游离钙及动脉平均压影响的临床意义

本研究发现,Ⅱ期原发性高血压(EH)患者血浆心钠素(PANP)浓度低于对照组(P<0.001),而淋巴细胞内游离钙(Ca~(2 )L)则明显高于对照组(P>0.001);其中左心室肥厚(LVH)组PANP及Ca~(2 )L均显著高于左室非肥厚(NLH)组;硝苯地平对LVH组PANP、Ca~(2 )L及平均动脉压(MAP)的降低程度均明显大于NLH组。     

硝苯地平与卡托普利联合治疗尿毒症合并难治性高血压病的临床疗效观察

目的：观察硝苯地平与卡托普利联合治疗尿毒症合并难治性高血压病的临床疗效。方法：选取信宜市人民医院2013年9月—2014年9月收治的尿毒症合并难治性高血压病患者126例,以随机数字表法分为3组各42例。对照A组患者给予硝苯地平治疗,对照B组患者给予卡托普利治疗,观察组患者给予硝苯地平与卡托普利联合治疗,观察并比较3组患者的临床疗效、肾功能变化、血压变化、平均血压达标时间及不良反应发生情况。结果：观察组患者总有效率为88．09％（37／42）,明显高于对照A组的66．67％（28／42）、对照B组的61．90％（26／42）,差异均有统计学意义（P＜0．05）;治疗后,观察组患者的舒张压、收缩压显著低于对照A组、对照B组,且平均血压达标时间明显短于对照组A、B组,差异均有统计学意义（ P＜0．05）。结论：硝苯地平与卡托普利联合治疗尿毒症合并难治性高血压病,较单药治疗的效果更为确切。     

硝苯地平缓释片(I)的释放度差异性研究

目的：考察硝苯地平缓释片的释放度（I）控制情况。方法：通过不同厂家、不同处方工艺的硝苯地平缓释片（I）和不同仪器的释放度检测结果,反映硝苯地平缓释片（I）释放度的差异性。结果与结论：硝苯地平缓释片释放度检测结果符合质量标准要求,但制剂批的质量一致性有待提高,明确需进行工艺或质量检测方法研究,进行体内外溶出相关性的评价工作。