硝苯啶对心绞痛患者血液流变学作用

<正> 钙通道阻滞剂抑制离子进入细胞内,也抑制心肌细胞兴奋—收缩耦联中钙离子利用,因而抑制心肌的收缩,减少心肌耗氧,影响多种腺体分泌,抑制血小板聚集,改进低氧血症时血液流变学异常,改善红细胞变形性。我们对25例口服硝苯啶的心绞痛患者的血液流变学进行研究,旨在探讨硝苯碇对该类患者血流变学影响。     

硝苯啶对稳态时氨茶碱药物动力学和药效学的影响

本文报告了１０名慢性阻塞作肺疾病（ＣＯＰＤ）患者服用硝苯啶前后稳态时氨茶碱药物动力学和药效学的变化，整个实验分二个期，Ⅰ期为单服氨茶碱３天至稳态；Ⅱ期为二药合并用药５天。各期测得的氨茶碱药物动力学参数，Ｃ＾ｓ＾ｓＴＰＫ分别为１２．９１，１１．３μｇ／ｍＬ；ＣＬ＾ｓ＾ｓ分别为０．０４５，０．０５２Ｌ／ｈＫｇ；ｔ１／２分别为１０．０９，９．３４ｈ；Ｖｄ＾ｓ＾ｓ分别为０．６２８，０．６４５Ｌ／Ｋｇ。药效     

硝苯吡啶和间硝苯啶扩血管降压作用的比较

本实验比较了硝苯吡啶与间硝苯啶的降压作用与持续时间、血流动力学效应及光稳定性。结果表明,二者均具有明显的扩血管降压作用。硝苯吡啶和间硝苯啶引起麻醉大鼠血压下降的ED_(50)分别为0.25±0.13和0.20±0.07μmol/kg;iv 50μg/kg其作用持续时间为68±48和58±30min;间硝苯啶对光稳定,而硝苯吡啶曝光3h则丧失降压活性。     

间硝苯啶与美托洛尔合用对兔血液动力学的影响

用阻抗法测定间硝苯啶(m-Nif)和美托洛尔(Met)对清醒兔血液动学力的影响。m-Nifiv(20μg/kg)或十二指肠给药(0.25 mg/kg)可增加心脏指数、降低总外周阻力及血压,而对心率无影响。m-Nif与等量或5倍量Met合用时,可减慢心率,并保持m-Nif的上述作用。m-Nif与两种剂量Met合用的作用差别是后者心率减慢更为明显。结果提示,m-Nif与小剂量Met合用是可取的,尤其在高血压和冠心病伴有心率增快的患者是有利的。     

硝苯啶合并普萘洛尔治疗原发性高血压38例

本文报告钙通道阻滞剂硝苯啶合并β阻滞剂普萘洛尔治疗原发性高血压38例6mo。疗效观察:硝苯啶口服起效时间15-30min,高峰时间1-1.5h,和普萘洛尔联用服6mo后,药效可维持36-48h,72h仍能低于基础血压。平均降压5.6/2.6kPa(42.1/19.4mmHg),总有效率达97％。经随机分组30例作同期对照,结果表明,两药并用,剂量小,副作用少,效果显著。是一组简便、速效、安全的药物组合,用于重症高血压应急处理和慢性高血压维持治疗。     

硝苯毗啶治疗高血压病69例

硝苯吡啶又名心痛定，是一种钙阻泄剂，有扩张血管作用。除治疗冠心病心绞痛外，还广泛用于高血压病的治疗。现将我院87年至88年6月用硝苯吡啶治疗高血压69例，报告如下。     

间硝苯啶与硝苯啶对急性心肌缺血大鼠左心室舒张功能的影响

结扎大鼠冠脉引起T值延长,-dP/dt_(max)和-dP/dt_(max)·LVSP~(-1)降低、LVEDP抬高等心肌舒张功能降低的改变。预先分别iv M-Nif,Nif 15μg/kg均能不同程度地改善急性缺血心肌的舒张功能,其中M-Nif作用较强。此外,iv M-Nif尚有一过性增强舒张功能的作用。     

邻氯间硝苯啶的合成

据报道,邻氯间硝苯啶[2,6-二甲基-4-(2-氯-3-硝基苯基)-1,4-二氢吡啶-3,5-二甲酸二甲酯,1]与血管舒张感受器有较好的亲和性,是有希望的血管扩张剂。本文     

Acute and chronic effects of nifedipine in arterial hypertension

Summary Sublingual administration of nifedipine 10 mg to 11 patients and 20 mg to 6 patients with arterial hypertension caused a rapid and significant decrease in blood pressure in both groups. The average maximal reductions in the two groups were 21/16 mm Hg and 27/21 mm Hg. A concomitant rise in heart rate was found. Forearm blood flow showed a significant increase and the calculated vascular resistance a significant decrease 15–60 min after administration of both the 10 mg and the 20 mg doses. There was a negative correlation between basal vascular resistance and the maximal change of this parameter (r=–0.72, p<0.01). Plasma concentrations of nifedipine showed considerable individual variation, with slow absorption in some patients, which indicated failure of sublingual absorption in them. The difference between the mean plasma concentration in the two dose groups was statistically significant after 45 min. A negative correlation was present between the plasma concentration of nifedipine and the observed change in calculated vascular resistance (r=–0.74 at t=30 min). Treatment of 10 hypertensive patients with nifedipine 30–60 mg daily for 6 weeks reduced mean blood pressure from 175/115 mm Hg to 151/96 mm Hg (p<0.001). Heart rate and forearm blood flow rose, whereas the forearm vascular resistance showed a significant decrease. Side effects of a sensation of heat and reddening of face were noted in some patients. It is suggested that nifedipine may be useful both in the acute and chronic treatment of arterial hypertension.     

硝苯地平缓释剂联合利尿剂治疗173例老年高血压患者安全性与有效性临床观察

目的探讨硝苯地平缓释剂联合不同利尿剂(氢氯噻嗪和吲达帕胺)的治疗方案对老年高血压患者的降压安全性及有效性,以寻找适合我国老年高血压患者的降压方案。方法将173例老年高血压患者随机分为3组,Nif组服硝苯地平缓释片10 mg/次,2次?d-1;Nif+HCTZ组在服用硝苯地平基础上加服氢氯噻嗪,剂量为12.5 mg/次,1次?d-1,Nif+ID组在服用硝苯地平基础上加服吲达帕胺,剂量为2.5 mg/次,1次?d-1,疗程8周,考察用药期间血压的变化,进而评价3种用药方案的有效率及安全性。结果 Nif组平均坐位血压从(172.4±12.3)/(101.4±8.6)mmHg降为(150.9±11.6)/(86.4±7.1)mmHg;Nif+HCTZ组平均坐位血压从(176.7±13.6)/(100.8±7.65)mmHg降为(139.7±12.7)/(81.3±8.2)mmHg;Nif+ID组平均坐位血压从(175.4±11.8)/(105.2±9.03)mmHg降为(142.5±10.8)/(81.6±8.6)mmHg。2种联合用药方案有效率与Nif组降压有效率相比,差异有统计学意义(P<0.01),对血钾和肾功能影响差异无统计学意义。主要不良反应为颜面潮红和踝部水肿,Nif+HCTZ组及Nif+ID组比Nif组老年患者不良反应明显减少。结论硝苯地平缓释剂联合利尿剂氢氯噻嗪或吲达帕胺,降压有效率高于单用硝苯地平缓释剂,对老年高血压患者代谢无影响,是老年高血压的有效治疗方案。     

间硝苯地平与硝苯地平对肾血管性高血压大鼠血流动力学影响

问硝苯地平(m-Nif)和硝苯地平(Nif)20mg·kg~(-1)·d~(-1),ig,9wk,对大鼠银夹左肾动脉所致肾血管高血压模型能明显降低高血压,预防和逆转肾血管高血压所引起的心肌肥厚,在离体工作心脏,心肌的收缩和舒张功能及血流动力学参数均得到明显改善,心脏湿重减轻,表明m-Nif和Nif具有防治高血压心肌肥厚,改善心脏血流动力学的作用。     

Dose adjustment of nifedipine in hypertensive patients

Summary Ten patients with essential hypertension (WHO grade I–II) were treated in an open dose-adjustment study with the standard regimen of slow-release nifedipine 20 mg b. d. for 2 weeks and with an individualized dose for 6 weeks. The optimum dose, defined as that producing a pre-dose diastolic blood pressure (dBP) of 90 mm Hg at steady state, was determined from the individual concentration-effect relationship after a test-dose of 20 mg.On standard therapy, the reduction in pre-dose dBP was inadequate in 4 patients and it was excessive in 1 patient. After 2 weeks of individualized treatment, the required pre-dose antihypertensive effect was obtained in all patients. The individual doses required were 10 mg b. d., 10 mg t. d. s. 20 mg b. d., 20 mg t. d. s. and 20 mg q. d. s.One patient dropped out of the study because of side effects. Loss of the antihypertensive effect was observed in one patient after 6 weeks of treatment.On the optimized dose, the average value of the pre-and 2 h post-dose steady state nifedipine concentrations (27.6 g/l) compared well with model-derived optimum concentrations (28.6 l/l) (r=0.9210).The results show that the dose of nifedipine can be accurately predicted using the individual concentration-effect relationship after a single dose.     

Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study

AIMS: As melatonin has been found to play a role in the mechanisms of cardiovascular regulation, we designed the present study to evaluate whether the evening ingestion of the pineal hormone might interfere with the antihypertensive therapy in hypertensive patients well-controlled by nifedipine monotherapy. METHODS: Forty-seven mild to moderate essential hypertensive outpatients taking nifedipine GITS 30 or 60 mg monotherapy at 08.30 h for at least 3 months, were given placebo or melatonin 5 mg at 22.30 h for 4 weeks according to a double-blind cross-over study. At the end of each treatment period patients underwent a 24 h noninvasive ambulatory blood pressure monitoring (ABPM) during usual working days; sleeping period was scheduled to last from 23.00 to 07.00 h. RESULTS: The evening administration of melatonin induced an increase of blood pressure and heart rate throughout the 24 h period (DeltaSBP = + 6.5 mmHg, P < 0.001; DeltaDBP = + 4.9 mmHg, P < 0.01; DeltaHR = + 3.9 beats min-1, P < 0.01). The DBP as well as the HR increase were particularly evident during the morning and the afternoon hours. CONCLUSIONS: We hypothesize that competition between melatonin and nifedipine, is able to impair the antihypertensive efficacy of the calcium channel blocker. This suggests caution in uncontrolled use of melatonin in hypertensive patients. As the pineal hormone might interfere with calcium channel blocker therapy, it cannot be considered simply a dietary supplement.     

硝苯啶与卡托普利合用治疗重症高血压和慢性心力衰竭

作者以硝苯啶与卡托普利联合服用治疗重症原发性高血压和慢性充血性心力衰竭病人各7名。观察短期血流动力学变化。临床结果表明,联合服用后的抗高血压作用较明显;心衰病人的心功能也有显著改善。这表明机理不同的血管扩张药物联合应用后可能起到协同作用。因此,长期口服血管扩张药物联合治疗心血管疾病是合理的。     

Comparison of guanabenz and clonidine in hypertensive patients

Summary

The antihypertensive and clinical effects of two centrally acting drugs, guanabenz and clonidine, were compared in a double-blind trial in 29 patients with established hypertension. After a 1-week baseline period and 2 weeks on placebo, patients received treatment with either guanabenz (mean dose 24?mg daily) or clonidine (mean dose 0.45?mg daily) alone for 8 weeks. Both drugs produced equivalent and highly significant (p < 0.001) reductions in systolic and diastolic blood pressures in the standing and supine positions. They also reduced significantly the standing and supine pulse rates. Normal orthostatic responses were maintained with both regimens. AN but 1 patient in each group reported side-effects during active treatment, the most frequent being dry mouth and sedation with each drug. No laboratory or ECG abnormalities related to treatment were observed.     

Vascular and cardiac effects of HP 406 and nifedipine in vitro and in conscious spontaneously hypertensive rats and renal hypertensive dogs

The cardiovascular effects of the calcium antagonists HP 406 and nifedipine were assessed in a series of in vitro and in vivo studies. HP 406 was found to display moderate affinity for dihydropyridine binding sites, as determined by the inhibition of [³H]-nitrendipine binding on rat ventricular membranes. HP 406 was found to have an IC₅₀ of 1.3 × 10^?7 M as compared to nifedipine with an IC₅₀ of 7.0 × 10^?9 M. Additional in vitro studies were conducted with isolated spontaneously contracting and electrically paced guinea pig atria and rabbit aortic rings. HP 406 was found to have minimal effects on cardiac chronotropic and inotropic activity in isolated guinea pig atria. In contrast, nifedipine caused significant dose-related reductions in heart rate and myocardial contractile force. Rabbit aortic rings were precontracted with potassium chloride (KCI) or norepinephrine (NE), and HP 406 or nifedipine was added to tissue baths in a cumulative dose range. HP 406 and nifedipine both caused dose-related relaxation of KCI- and NE-contracted rings; however, the IC₅₀'s against KCI were found to be significantly lower than those against NE for both compounds. The IC₅₀'s against NE were found to be 4.8 × 10^?8 M and 5.9 × 10^?8 M for HP 406 and nifedipine, respectively. The IC₅₀'s against NE were 1.9 × 10^?5 M for HP 406 and 4.4 × 10^?5M for nifedipine. Finally, the antihypertensive activity of HP 406 and nifedipine were compared in the spontaneously hypertensive rat (SHR) and renal hypertensive dog. Both compounds produced significant reductions in mean arterial pressure at 1 mgikg p.o. in the SHR and at 3 mgikg p.o. in the renal hypertensive dog. Nifedipine was also found to cause a significantly greater tachycardia compared to HP 406. The results of this study show that HP 406 is a potent antihypertensive agent with minimal direct or reflex-mediated chronotropic effects. The mechanism of this antihypertensive activity appears to result from calcium-channel antagonism and vascular dilation.     

Cross-over study of muzolimine and hydrochlorothiazide-amiloride in hypertensive patients

Summary Thiazide therapy is a widely used first line treatment for arterial hypertension. Its useful value, particularly in mild or moderate hypertension, is sometimes reduced by metabolic side-effects, as hypokalaemia and hyperuricaemia.In the present study the antihypertensive efficacy of a new, non-sulphonamide diuretic Bay g 2821 (muzolimine) was evaluated in comparison with the combination of hydrochlorothiazide-amiloride over a period of 4 weeks. A highly significant decrease in systolic and diastolic blood pressures was produced by both treatments.No decrease in serum potassium nor an increase in cholesterol, triglycerides, uric acid or glucose was detected during the 4 week treatment period. Subjective side-effects, such as headache and dizziness, were very rarely observed during Bay g 2821 treatment.The new diuretic appears, therefore, to be effective in the treatment of arterial hypertension without untoward side-effects.     

A double-blind comparison of indoramin and propranolol in the treatment of moderate to severe essential hypertension

Summary

In a double-blind study, patients with moderate to severe essential hypertension were treated randomly with either indoramin or propranolol orally. The dose of both drugs was increased as necessary, to a predetermined level, in order to reduce the diastolic (Phase V) blood pressure to 100 mmHg or less. Patients were followed up for 12 weeks. There were 23 patients on propranolol and 27 on indoramin. The blood pressure in 22 patients on propranolol and 25 patients on indoramin was satisfactorily controlled in both the supine and standing positions. Mean supine blood pressure decreased from 181.3±14.2/116.2±6.8 mmHg to 140.6±7.1/95, 7±3.6 mmHg after 12 weeks of treatment in patients receiving propranolol and from 188.3±18.9/118.4±8.7 mmHg to 144.7±7.3/95.7±2.5 mmHg in those treated with indoramin. There were no significant differences between the effects on supine and standing blood pressures and blood pressure control was maintained throughout the 12-week period in patients receiving indoramin and those receiving propranolol. Propranolol reduced the mean heart rate by approximately 16 beats/min in both the supine and standing positions. The maximum effect was seen 4 weeks after starting treatment and was maintained throughout the study. Sinus bradycardia (heart rate <60/min) occurred in 9 (39%) patients receiving propranolol. Indoramin caused a small but significant reduction in mean heart rate of approximately 4 beatslmin in both the supine and standing positions. The maximum effect was seen after 2 weeks of treatment and was maintained for the rest of the duration of treatment. Eight (34.8%) patients on propranolol and 8 (29.6%) patients on indoramin experienced side-effects. These were mild to moderate in nature in the majority of cases. Fatigue and dizziness from indoramin and fatigue from propranolol were the commonest side-effects reported. Neither drug produced any significant alteration in the haematological and biochemical variables studied.