盐酸特拉唑嗪的药效学观察

目的：观察国产盐酸特拉唑嗪的降压作用。方法：观察单次和连续多次灌胃盐酸特拉唑嗪对自发性高血压大鼠和肾型高血压大鼠的降压作用。结果：盐酸特拉唑嗪单次灌胃给药剂量依赖性，降低自发性高血压大鼠的收缩压；连续2周灌胃给药剂量依赖性降低自发性高血压大鼠和肾型高血压大鼠的收缩压。结论：盐酸特拉唑嗪具有明显的降压作用。     

硝苯地平,阿替洛尔合用对大鼠自发性高血压及麻醉开胸犬？…

在所择剂量范围内硝苯地平-阿替洛尔复方单次、连续灌胃给药对自发性高血压大鼠均有明显降压作用。与硝苯地平、阿替洛尔单方比较,降压作用明显,且对心率无明显影响。对麻醉开胸犬有降低平均动脉压、减轻心脏负荷作用。     

盐酸特拉唑嗪的药效学观察

目的　 观察国产盐酸特拉唑嗪的降压作用。 方法 　观察单次和连续多次灌胃盐酸特拉唑嗪对自发性高血压大鼠和肾型高血压大鼠的降压作用。 结果 　盐酸特拉唑嗪单次灌胃给药剂量依赖性 ,降低自发性高血压大鼠的收缩压 ;连续 2周灌胃给药剂量依赖性降低自发性高血压大鼠和肾型高血压大鼠的收缩压。 结论 　盐酸特拉唑嗪具有明显的降压作用     

乌拉地尔治疗肾性高血压20例观察

目的观察乌拉地尔注射液对肾性高血压的临床疗效。方法肾性高血压20例,给予乌拉地尔注射液12.5mg静推,继以0.1~0.4mg/min的滴速持续静脉点滴,观察血压、心率变化及不良反应情况。结果乌拉地尔注射液治疗肾性高血压能很快控制血压,并且不增加心率,无严重不良反应。结论乌拉地尔治疗肾性高血压安全有效。     

地尔硫联合硝苯地平治疗肾移植并发高血压20例

目的：研究地尔硫、硝苯地平联合用于环孢素治疗肾移植并发高血压的长期疗效。方法：将40例经环孢素治疗的肾移植并发高血压患者随机分为治疗组和对照组各20例，治疗组给予地尔硫，每次30 mg，po，bid；硝苯地平每次10 mg，po，tid。对照组只给予硝苯地平，用法同治疗组。根据血压控制情况，调整治疗组地尔硫和对照组硝苯地平剂量。对患者进行＞2 a的临床观察，观察患者血药浓度及动脉血压、肾功能。结果：地尔硫干扰环孢素代谢，导致环孢素剂量降低40.0%，但未见其增强环孢素肾毒性。两组的平均血压水平相似，维持在正常范围内。两组肾功能差异无显著性(P＞0.05)。结论：地尔硫、硝苯地平联用于肾移植并发高血压症，安全有效，并能节约肾移植患者的费用。     

地尔硫对高血压急性脑卒中病人的降压治疗

目的 :观察地尔硫在高血压急性脑卒中病人中的降压作用。方法 :有急性脑卒中的高血压病人 6 5例 ,根据血压值不同 ,分为A组 31例 ,先采用地尔硫针剂 5 0mg溶于氯化钠注射液或 5 %葡萄糖注射液 2 5 0mL中 ,iv ,gtt ,2～ 4h滴完。 2 4h后 ,采用地尔硫缓释片剂 90mg ,po ,qd ,服用2wk。B组 34例 ,采用地尔硫缓释片剂 90mg ,po ,qd ,服用 2wk。结果 :A组和B组用药后d 14降压有效率分别为 90 %与 88% ,P >0 .0 5。A组病例静脉用药后 10 ,2 0 ,30 ,6 0 ,12 0min血压降压幅度与其前一观察时刻的血压值差别有显著意义 ,降压安全性达 90 %。 2组病例治疗后d 1,2 ,7,14的血压降压幅度与其前一观察值差别均有显著意义 ,治疗后d 7,14神经功能缺损评分和日常生活活动Barthel指数 ,与用药前比较差别均有显著意义。所有病例用药后不良反应轻微。结论 :地尔硫对高血压急性脑卒中病人的降压疗效确切、安全性高。     

褐藻氨酸对肾性高血压大鼠的降压作用

目的：探讨褐藻氨酸的降压作用。方法：用肾外包扎法使大鼠形成肾性高血压模型。模型组分为高剂量组（300μg/kg），低剂量组（150mg/kg)，并设阳性对照组和阴性对照组，均行灌胃，每天1次，共20天。结果：低剂量组大鼠血压降低20．2％，高剂量组降低26．2％，与生理盐水组比较均有非常显性差异（P＜0．01）。结论：褐藻氨酸对肾性高血压大鼠具有降压作用。     

甜菊苷对大鼠及犬的降血压作用

目的：评价甜菊苷的抗高血压作用。方法：采用动静脉插管术研究甜菊苷静脉注射对清醒及麻醉自发性高血压大鼠和麻醉犬的降血压作用特点。结果：清醒自发性高血压大鼠甜菊苷５０～２００ｍｇ／ｋｇ,ｉｖ,麻醉自发性高血压大鼠甜菊苷２５～３９８ｍｇ／ｋｇ,ｉｖ麻醉犬甜菊苷１６～１５９ｍｇ／ｋｇ,ｉｖ,均可剂量依赖地降低收缩压和舒张压,降压持续时间延长,且降舒张压的作用较收缩压明显。自发性高血压大鼠甜菊苷６３～２５１     

乌拉地尔、硝酸甘油用于高血压急症院前急救的临床分析

目的观察乌拉地尔、硝酸甘油注射液对高血压急症的临床疗效,并分析其对心率的影响。方法将80例高血压急症患者随机分为乌拉地尔组与硝酸甘油组各40例。乌拉地尔组给予乌拉地尔注射液25mg用0．9％氯化钠注射液20mL稀释,5min内静脉推注,随后用乌拉地尔50mg加入0．9％氯化钠注射液250mL中静脉滴注,初始速度为0．5mL／min（100μg／min）;硝酸甘油组给予硝酸甘油注射液5mg加入0．9％氯化钠注射液250mL中静脉滴注,初始速度为0．5mL／min（10μg／min）。比较两组给药前后血压、心率变化。结果乌拉地尔组、硝酸甘油组均可明显降低高血压急症患者血压．达到治疗目标．两组间疗效比较无明显差异,硝酸甘油组治疗后心率明显增快,不良反应较多。结论乌拉地尔作用迅速、降压平稳．不良反应轻微．是高血压急症院前急救的理想药物。     

地尔硫卓注射液在血透治疗期间突发高血压的降压作用

目的观察在血透治疗期间突发高血压时静脉推注地尔硫卓的降压效果。方法25例血透患者,给予地尔硫卓注射液50mg加入5%葡萄糖注射液250ml中静脉推注,分别观察5、30、60min血压变化。结果5min内血压开始下降达至85%;30min内全部病例血压均有所下降;60min时血压达到正常范围内的病例数为60%。结论地尔硫卓注射液在血透治疗期间突发高血压降压效果明显,不良反应,平稳安全。     

Studies on the anti-vasoconstrictor activity of BRL 34915 in spontaneously hypertensive rats; a comparison with nifedipine.

1. The blood pressure lowering and anti-vasoconstrictor effects of BRL 34915 and nifedipine were compared in female spontaneously hypertensive rats (SHR). 2. In conscious SHR, intravenous injection of BRL 34915 (0.1, 0.3 mg kg-1) produced rapid, dose-related falls in mean arterial pressure of greater than 3 h duration. Nifedipine, at the same intravenous dose levels, also evoked rapid anti-hypertensive effects, though these responses were of lesser magnitude and duration than those observed for BRL 34915. 3. In anaesthetized, ganglion-blocked SHR, BRL 34915 (0.1, 0.3 mg kg-1 i.v.) dose-dependently antagonized the pressor responses to incremental intravenous infusions of noradrenaline (3.8-28.5 ng min-1) or phenylephrine (120-907 ng min-1) but did not inhibit pressor responses to incremental infusions of methoxamine (0.47-3.63 micrograms min-1), angiotensin II (7.0-52.9 ng min-1) or vasopressin (0.27-2.0 mu min-1). 4. In anaesthetized, ganglion-blocked SHR, nifedipine (0.1, 0.3 mgkg-1 i.v.) antagonized the pressor responses to each of the infused vasoconstrictor agents, being most effective against responses to noradrenaline or angiotensin II. 5. In pithed SHR, both BRL 34915 and nifedipine (each at 0.3 mg kg-1 i.v.) reduced the basal blood pressure level and produced marked inhibition of frequency-dependent pressor responses evoked by electrical stimulation of the spinal cord sympathetic outflow (0.25-4.0 Hz). Restoration of the basal diastolic blood pressure to within the control range, using a continuous intravenous infusion of vasopressin (0.98 mu min-1), prevented the inhibitory effect of BRL 34915. In the case of nifedipine, however, even raising the basal blood pressure to a level exceeding that recorded in control rats (with vasopressin, 2.0 mu min-1), did not reverse the inhibitory effect of the drug on frequency-dependent pressor responses. 6. It is concluded that the anti-hypertensive properties of BRL 34915 in SHR are probably unrelated to an anti-vasoconstrictor action. In contrast, it is suggested that the broadly-based anti-vasoconstrictor properties of nifedipine may contribute substantially to the anti-hypertensive properties of this drug.     

Pharmacokinetics and pharmacodynamics of nifedipine infusion in normal volunteers.

Two studies of the pharmacokinetics and pharmacodynamics of intravenous nifedipine infusion were performed: the first, a randomised double-blind crossover study of nifedipine and its vehicle in eight subjects, the second a dose ranging study in nine subjects. Nifedipine pharmacokinetics did not vary with dose or duration of infusion up to 8 h, and are similar to those reported for other nifedipine preparations. Nifedipine increased heart rate and forearm blood flow and decreased blood pressure after bolus injection but not during prolonged infusion. The vehicle decreased blood pressure and increased forearm blood flow after bolus injection but not during prolonged infusion. It did not affect heart rate. The vehicle's haemodynamic activity has not been previously recognised and is of potential importance in the study of this and similar preparations of calcium antagonists.     

Dose response and length of action of nifedipine capsules and tablets in patients with essential hypertension: A randomised crossover study

Summary Twelve patients with essential hypertension on no other drug treatment were entered into a randomised crossover study of 5, 10 and 20 mg capsules of nifedipine given 3 times a day and 20 mg tablets given twice a day. Each dose was given for 2 weeks in a random order. All forms of nifedipine were effective in lowering blood pressure.However, 5 mg capsules were less effective than the 10 and 20 mg capsules or 20 mg tablets. There was little to choose between the latter. All doses of nifedipine were more effective 1 and 3 h after the dose compared to subsequent times afterwards. Indeed, as time elapsed after the last dose up to 12 h, there was a gradual increase in blood pressure. However, even at 12 h the 10, 20 mg capsules and 20 mg tablets were still causing an approximate 10% reduction in blood pressure.Nifedipine tablets are as effective as capsules though they might be longer acting, particurarly around 6 h after the last dose.     

Blood pressure response to enalaprilic acid in essential hypertension: Dose-response and effect of pre-treatment with furosemide

Summary Enalaprilic acid (MK 422), the active metabolite of enalapril, has recently become available for intravenous administration. In order to establish the proper dose for rapid blood pressure reduction, 9 patients with moderate to severe essential hypertension on a constant sodium intake of 100 mmol/24 h were studied. They received four single doses of MK 422 according to an up-and-down titration schedule. Doses between 5 and 80 mg resulted in effective blood pressure reduction with an onset of action of about 10 minutes. Within this dose range the response was flat. No symptomatic hypotension was observed. The fall in blood pressure was less pronounced in patients with low initial plasma renin activity (PRA). Accordingly, a study was done to show whether the blood pressure response could be augmented by preceding stimulation of PRA by injection of 40 mg furosemide 15 minutes before the administration of MK 422. PRA increased after furosemide, but the blood pressure response to MK 422 was not augmented.     

The effect of calcium channel blockade with nifedipine on splanchnic and systemic haemodynamics in cirrhosis

The splanchnic and systemic haemodynamic effects of a single sublingual dose of nifedipine (slow calcium channel blocker) in nine patients with cirrhosis of the liver and portal hypertension were studied. Nifedipine produced a significant reduction in the mean arterial blood pressure (98 +/- 5.3 vs. 86 +/- 5 mmHg, P less than 0.05) but did not alter the mean heart rate, portal venous pressure or total liver blood flow. The systemic antihypertensive effect of nifedipine can be achieved without altering liver blood-flow in patients with chronic liver disease and portal hypertension.     

Evaluation of the method for nifedipine administration for a rapid onset of clinical effect: a clinical study in normal volunteers

Nifedipine is frequently used for patients who require an immediate reduction of blood pressure elevated temporarily by various administration techniques including sublingual route without administrating intravenous infusion of vasodilator. A cross-over clinical study was conducted to investigate the optimal administration method of nifedipine for rapid management of hypertension. Four method of administering 10 mg nifedipine (the capsule was bitten and swallowed, sublingually with a hole in it or the contents administered orally or intranasally with a syringe) were evaluated with regarded efficacy, safety, and usefulness in 6 normal volunteers. Systolic and diastolic blood pressures were correlated with the nifedipine serum concentration in each method. Nifedipine pharmacokinetic parameters differed among the 4 administration methods. Nifedipine was absorbed rapidly by not only intestinal mucosa but also the nasal or oral mucosa. The pharmacological effect of intranasal or sublingual administration was superior. However, mint oil which is present in nifedipine capsules stimulates nasal mucosa when administered intranasally. For clinical usage, nifedipine capsules in which a hole is made with a needle, administered sublingually, can be effectively and safely used for rapid management of systemic hypertension.     

Antihypertensive effects of amlodipine, a new calcium antagonist]

The antihypertensive effects of oral administration of amlodipine (AML), a new calcium antagonist, were investigated in hypertensive animals. AML (1-10 mg/kg) produced a dose-dependent reduction of blood pressure (BP) in spontaneously hypertensive rats (SHR). The effect of AML reached a maximum at 4-6 hr and was sustained even at 10 hr post-dose, in contrast to the case of nifedipine that produced a maximum effect at 1 hr with a rapid recovery. Heart rate (HR) was increased slowly and slightly by AML (10mg/kg), but increased rapidly and markedly by nifedipine (3, 10 mg/kg). The dose (ED 30) of AML required to decrease BP by 30 mmHg was 2.3 mg/kg and similar to the case of nifedipine. AML also produced long-lasting reduction of BP in renal and DOCA hypertensive rats. The ED30 values were 2.4 and 2.2 mg/kg and similar to the respective values of nifedipine (ED 30:2.4,2.1 mg/kg). In renal hypertensive dogs (RHD), the effect of AML (0.1,0.3,1.0 mg/kg) was maximum at 4-6 hr and long-lasting, producing similar reductions of both systolic and diastolic BP (ED30: 0.3-0.4 mg/kg respectively). In SHR (1 or 3 mg/kg/day, for 15 days) and RHD (0.2 mg/kg/day for 20 days) chronically receiving AML, there was an enhancement of the antihypertensive effect of AML within a few days after starting chronic dosing, and thereafter a significant reduction of BP at 24 hr after dosing and constant effects of AML during subsequent treatment. BP after cessation of the chronic dosing gradually recovered to the level before the start of the experiments. No significant changes in HR were observed throughout the experiments. These results indicate that AML produces the antihypertensive effect with a similar potency to nifedipine but with a profile of slow onset and long duration, and there was no development of tolerance to the antihypertensive effects and changes of HR during long-term treatment.     

Nifedipine in the treatment of difficult hypertensives

Summary Nifedipine has been assessed as a possible alternative to other third line drugs in the management of patients with difficult to control hypertension. A group of 20 patients whose blood pressure was unsatisfactory on a 3 drug regimen had their third drug stopped and after a 2 week period nifedipine was added to their beta-blocker plus diuretic therapy. Eleven became normotensive on 30 mg nifedipine daily and a further 6 on 60 mg daily; giving on overall success rate of 85%. This result was achieved with a reduction in side effects and an absence of any haemodynamic or metabolic complications.     

Nifedipine and nimodipine: effect on blood pressure and regional cerebral blood flow in conscious normotensive and hypertensive rats

The dose-dependent reduction of mean arterial pressure (MAP) in conscious spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) was more pronounced after intravenous nimodipine than nifedipine administration. Nimodipine (5 micrograms/kg) followed by infusion of 0.75 microgram/kg/min lowered the blood pressure by 10% in both normotensive and hypertensive rats; the same dose schedule of nifedipine did not lower MAP. Neither drug altered the regional cerebral blood flow (rCBF) in this dose. After 50 micrograms/kg nimodipine were administered, followed by 7.5 micrograms/kg/min nimodipine, MAP dropped 38% in WKY and 46% SHR; corresponding figures for nifedipine were 13 and 17%. In spite of the reduction in MAP and a concomitant decrease in PaCO2, rCBF increased significantly in 19 of 23 regions studied after nifedipine and in 15 regions after nimodipine in SHR. The increase in rCBF in WKY was slight and insignificant in most areas. Thus, both calcium entry blockers reduced the cerebrovascular resistance more in SHR than in WKY.     

Antihypertensive and hormonal effects of single oral doses of Captopril and Nifedipine in essential hypertension

Summary In a single-dose crossover study Captopril (SQ 14225), 1 mg/kg body weight, and Nifedipine (Bay a 1040) 20 mg were administered orally to 12 hospitalized patients with essential hypertension (Stage 1 or 2, W. H. O.). Both drugs significantly reduced blood pressure, but each dose acted differently: the mean maximum arterial pressure reduction was faster and greater with Nifedipine than with Captopril: –23±2% at 37±15 min and –17±1% at 86±25 min, respectively. Captopril inhibited angiotensin II and aldosterone production, but did not accelerate heart rate or stimulate vasopressin release. Nifedipine stimulated vasopressin release and increased heart rate, but the renin angiotensin aldosterone system was not significantly affected. The blood pressure reduction was related to the initial level of activation of the renin angiotensin system only for Captopril. The blood pressure reduction induced by one drug was not related to that produced by the other in the same patient.