倍他洛尔

倍他洛尔(betaxolol,商标名称 Kerlone)为特异性肾上腺素神经β_1-受体阻滞剂,新近在美国批准用于降低血压及减慢心率。倍他洛尔对β-受体的阻断作用比普萘洛尔(心得安)更强。对正常人因运动而心率加速者,其减慢心率的效应为普萘洛尔的4倍。它对受体没有局部激动作用,仅有微弱的膜稳定作用。对动物或人,它抑制异丙肾上腺素产生的正性频率作用,并降低血压,还抑制肾上腺素对狗产生的室性心律失常,但不能抑制洋地黄产生的异位心律。     

美托洛尔治疗急性心肌梗死患者达不同目标心率对一年预后的影响

现在临床已广泛应用β受体阻滞药治疗急性心肌梗死(AMI),且以减慢心率为目标,但心率减少至多少为宜,尚未有更多国人的数据。本研究旨在探讨美托洛尔治疗急性心肌梗死患者达不同目标心率对一年预后的影响。     

施泰可

名 称:盐酸索他洛尔片(Sotalol Hydrochloride Tablets) 商品名:施泰可~(TM)(Sotacor Tablets)。 特 点:施泰可兼有Ⅱ类(β-肾上腺素受体阻断药)和Ⅲ类(延长心肌动作电位复极时间)抗心律失常药特性。索他洛尔非选择性阻断β-肾上腺素受体,但无内在拟交感活性和膜稳定作用,小剂量时,表现出β-受体作用,可延长窦房周期和房室(AV)结不应期,减慢房室传导(延长AV时间);较大剂量时可延长心房、心室动作电位时间和有效不应期(ERP),在体表心电图上表现为QT间期及心率校正QT(QTc)间期延长,表现出Ⅲ类抗心律失常药特征。索他洛尔与胺磺酮不同.不抑制心肌动作电位O相去极化速率(Vmax),对QRS波和 HV间期无影响。     

β受体阻滞剂美托洛尔注射剂临床评价

β受体阻滞剂自1975年开始用于治疗心力衰竭。随后的大规模临床试验表明在常规治疗的基础上加用卡维地洛、美托洛尔、比索洛尔可降低病死率，而应用布辛洛尔的试验未取得阳性结果。目前被证实有效的β受体阻滞剂具有不同的肾上腺素能受体选择性和附加特性。我们现在探讨一下β受体阻滞剂美托洛尔的临床疗效。     

新药橱窗

名称:盐酸索他洛尔片(Sotalol Hydrochloride Tablets) 商品名:施泰可~(TM)(Sotacor Tablets)。 特点:施泰可兼有Ⅱ类(β-肾上腺索受体阻断药)和Ⅲ类(延长心肌动作电位复极时间)抗心律失常药特性。索他洛尔非选择性阻断β-肾上腺素受体,但无内在拟交感活性和膜稳定作用,小剂量时,表现出β-受体作用,可延长窦房周期和房室(AV)结不应期,减慢房室传导(延长AV时间);较大剂量时可延长心房、心室动作电位时间和有效不应期(ERP),在体表心电图上表现为QT间期及心率校正QT(QTc)间期延长,表现出Ⅲ类抗心律失常药特征。索     

新药橱窗

名称:盐酸索他洛尔片(Sotalol Hydrochloride Tablets) 商品名:施泰可~(TM)(Sotacor Tablets)。 特点:施粲可兼有Ⅱ类(β-肾上腺素受体阻断药)和Ⅲ类(延长心肌动作电位复极时间)抗心律失常药特性。索他洛尔非选择性阻断β-肾上腺素受体,但无内在拟交感活性和膜稳定作用,小剂量时,表现出β-受体作用,可延长窦房周期和房室(AV)结不应期,减慢房室传导(延长AV时间);较大剂量时可延长心房、心室动作电     

新型肾上腺素β受体阻滞药奈必洛尔在心血管疾病中的应用进展

奈必洛尔是一种新型的第三代肾上腺素β受体阻滞药,对β_1受体具有高选择性,可通过内皮L-精氨酸/一氧化氮途径扩张血管,清除自由基,改善内皮功能,还具有不干扰糖脂代谢、抗血小板聚集等优点。本文综述了奈必洛尔的结构特点、药动学、作用机制和临床研究进展。     

普萘洛尔的临床应用

普察洛尔（心得安）为β肾上腺能受体阻滞剂,主要用于心律失常、心绞痛、高血压、甲状腺功能亢进。近年来随着大量心血管新药的应用,使普萘洛尔在心血管方面已失去昔日的辉煌,而在心外疾病的用途却大为拓宽,现综述如下。1治疗门脉高压食管胃底曲张静脉出血苦茶洛尔阻滞心脏β受体使心率减慢,心输出量减少,内脏血流减少。同时阻滞内脏血管的β2受体反射性地使内脏血管α受体活性增强,内脏动脉收缩,门脉下降。其有效剂量指使心率减少25％的剂量,其时心输出量减少30．7％,门脉压下降25％．一般以40mg为首次剂量,可逐渐增至有效剂量4…     

兰地洛尔的药理作用及其围手术期的应用

兰地洛尔是一种新型超短效心脏高选择性的肾上腺素β_1受体(β_1受体)阻断药,β_1/β_2为255,t_(1/2)短(3.5 min)。主要用于治疗手术时心动过速性心律失常(心房纤维性颤动、心房扑动及窦性和室上性心动过速)。兰地洛尔选择性高,其负性变时作用比艾司洛尔强,而负性变力作用比艾司洛尔弱,两者之比较艾司洛尔高,是围手术期一种更安全的β_1受体阻滞药。本文综述兰地洛尔的药理作用及其临床应用。     

不同β受体阻滞药对老年男性原发性高血压骨质代谢的影响

目的:观察不同β受体阻滞药对老年男性原发性高血压病人骨密度(BMD)及骨折发生率的影响。方法:随机连续选择年龄>60岁的老年男性原发性高血压患者350例。按干预方式不同,分为比索洛尔组99例(5～10mg.d-1,qd);美托洛尔组95例(25～50mg.d-1,bid);阿替洛尔组83例(12.5～25mg.d-1,tid);对照组73例(未服用β受体阻滞药)。服用β受体阻滞药患者用药时间均在>3年。分别比较组间血清钙磷浓度、碱性磷酸酶浓度、骨密度、骨折发生率。结果:各治疗组血钙浓度、血磷浓度、碱性磷酸酶浓度与对照组间各相应数据比较,差异均无统计学意义(P>0.05);各治疗组骨密度与对照组间比较,有显著性差异(比索洛尔组1.49±0.12g.cm-2、美托洛尔组1.45±0.11g.cm-2、阿替洛尔组1.41±0.13g.cm-2与对照组1.11±0.17g.cm-2比较,P<0.05);各治疗组间骨密度比较,差异均无统计学意义(P>0.05);各治疗组骨折发生率较对照组比较有下降趋势,但组间比较差异无统计学意义(比索洛尔组骨折发生率7.07%、美托洛尔组骨折发生率6.32%、阿替洛尔组骨折发生率7.23%与对照组骨折发生率10.96%比较,P均>0.05);各治疗组间骨折发生率比较,差异均无统计学意义(P>0.05)。结论:长期服用治疗剂量β受体阻滞药(比索洛尔或美托洛尔或阿替洛尔)的老年男性原发性高血压患者的骨密度下降程度明显减轻,骨折发生率下降。     

社区开展高血压管理过程中高血压的控制效果分析

目的评价社区血压管理模式实施1年后高血压患者的血压控制效果。方法用自身对照实验的方法,比较社区内628名自愿参加研究的高血压患者在实施高血压管理方案1年后与实施前的血压控制效果的变化。结果相比于高血压控制干预前,干预后的患者平均收缩压降低5.91mmHg,平均舒张压降低4.77mmHg,差异具有统计学意义(P<0.05),治疗依从比率增加了28.6%,血压达标率增加了20.7%,差异具有统计学意义(P<0.05)。结论社区开展高血压控制管理能显著提高高血压患者的治疗依从性和血压达标率,有效降低血压,有利于改善患者健康情况。     

Chronic ouabain treatment enhances cardiac myosin ATPase activity in rats

1. Chronic ouabain administration increases blood pressure and produces a positive inotropic effect. However, the temporal changes capable of affecting both arterial and ventricular pressures and myosin ATPase activity during the induced hypertension have not been determined. 2. The aim of the present study was to investigate the time-course of the induction of hypertension to define when changes occur in Wistar rats treated with 25 mg/kg per day, s.c., ouabain for 3, 7, 15 or 30 days. 3. In anaesthetized rats, diastolic blood pressure increased after 7 days treatment with ouabain and after 15 and 30 days treatment, increases were observed in systolic blood pressure, left ventricular systolic pressure and myosin ATPase activity. After 15 days treatment, heart rate (HR) also increased, but after 30 days treatment HR returned to control levels. However, only after 30 days treatment did the left ventricular positive and negative first derivatives of intraventricular pressure (dP/dt(max) and dP/dt(min), respectively) increase. Increased arterial and left ventricular systolic pressures and myosin ATPase activity observed after 15 days treatment maintained similar levels as those after 30 days treatment. 4. The results suggest that changes in arterial and left ventricular pressures, HR and myosin ATPase activity induced by chronic ouabain treatment are time dependent, increasing after 15 days treatment. After 30 days treatment, the increase in systolic and diastolic arterial and ventricular pressures remained stable, as did inotropism. Normalization of HR after 30 days treatment suggests that during the period from Day 16 to Day 30 ouabain-induced hypertension is dependent, at least in part, on increased sympathetic activity.     

滋肾缓肝煎联合硝苯地平控释片对高血压患者的观察研究

目的：观察研究滋肾缓肝煎联合硝苯地平控释片对高血压患者的临床疗效。方法：收集整理62例高血压患者的临床资料,均采用滋肾缓肝煎联合硝苯地平控释片治疗,以4周为1个疗程,观察疗效,定期观察患者血压夜间下降率和夜间血压负荷的情况。结果：患者血压下降率及血压负荷下降明显,夜间的收缩压、舒张压最大及最小值清晰,高血压症状得以控制;不同疗程相比具有统计学意义。结论：滋肾缓肝煎联合硝苯地平控释片干预降压疗效确切。     

Effect of sustained-release verapamil therapy on the blood pressure at rest and on the pressor response to isometric exertion in hypertensive patients

Summary The effect of a new formulation of verapamil sustained release (SR) 240 mg tablets on resting blood pressure (BP) and on the pressor response to isometric exertion have been examined in a single-blind, placebo-controlled, cross-over study in 12 hypertensive patients (mean age 45 years).SR verapamil and placebo were administered every 12 h for 6 consecutive weeks. At the end of each period of treatment BP and heart rate (HR) were measured at rest and during isometric exercise, performed as a handgrip (HG) test for 3 min at 30% of the maximum voluntary contraction. There was a significant reduction in resting systolic and diastolic BP, with no change in HR. BP and HR at peak exercise were lower after verapamil than after placebo, but the maximal absolute increase did not change during verapamil therapy.The results are compatible with a role of SR verapamil b.d. in reducing resting BP in hypertension, and in lowering very high pressure at the peak of a HG test, without modifying the physiological reactivity of cardiovascular system.     

Investigations of the antihypertensive long-term action of candesartan cilexetil in different dosages under the influence of therapy-free intervals

INTRODUCTION: In a randomized, phase IV clinical study with 4 parallel treatment arms, the long-lasting treatment effect of candesartan cilexetil (CAS 145040-37-5, CC, Blopress) was to be demonstrated for a repeated therapy-free interval of 48 h in the dosages 8 and 16 mg with or without hydrochlorothiazide 12.5 mg (CAS 58-93-5, HCT; 4 groups totally). The reason for this design was the known possibility of missed tablet doses in the patients' daily practice leading to a not always sufficient lowering of blood pressure in essential hypertension. Therefore, the intake of the daily tablet dose was intentionally omitted twice (after 6 and 8 weeks) during the 8-week study treatment period. PATIENTS AND METHODS: Primary efficacy variable was the comparison of blood pressure lowering before and after the first 48-hour therapy-free interval following a 6-week treatment period. The confirmatory analysis was done on the basis of paired t-tests and the Bonferroni-Holm "step-down procedure" for the systolic and diastolic results in each of the four treatment groups. Secondary variables were the efficacy 24 and 48 h after the last tablet intake following a 6- and 8-week treatment period, the blood pressure normalization rate and the tolerability. 312 out-patients from 46 study centers in Germany with mild or moderate essential hypertension strictly treated according to the protocol requirements were evaluated in terms of all primary and secondary study parameters. The patient allocation to the 4 treatment arms as well as the conditions at study start concerning demographic data, physical investigation, patient history, ECG, concomitant diseases/therapy and baseline values of blood pressure were well comparable between the four groups. RESULTS: The antihypertensive therapy with CC showed the expected clear effect on blood pressure lowering in 312 per-protocol treated patients with in addition an increase for the higher dosages and for the combination with HCT. The mean rate of lowering (systolic/diastolic) after 24 h for all treatment groups together was 14.5/8.1 mmHg after 6 weeks and 17.3/9.5 mmHg after 8 weeks of therapy. The described antihypertensive blood lowering effect could be maintained in nearly 100% diastolic and 100% systolic values for the first 48-hour therapy-free interval after 6 weeks and in about 100% diastolic and 80% systolic values for the second interval after 8 weeks. These results could be reproduced without relevant differences for the respective single outcome in the four treatment groups. Regarding the primary study efficacy criterion the achieved lowering of blood pressure was highly statistically significant with p-values < 0.0001 in all 4 groups both for systolic and diastolic results. In addition, the long-term action over 48 h could be confirmed by the specific analysis according to Bonferroni-Holm showing that the p-values of all eight hypotheses were below the adjusted significance levels, i.e. in terms of the systolic and diastolic endpoints within the 4 treatment groups. Furthermore, statistically significant differences between the four treatment arms could not be detected regarding the long-lasting blood pressure lowering effect over As for tolerability the entire study provides no evidence on new or unknown pathologic drug reactions as well as on a frequent occurrence of specific adverse events or relevant laboratory changes. CONCLUSIONS: The objectives of the present study were completely met by confirming statistically and clinically the assumption of a clear, long-lasting, safe and metabolically neutral action of CC both for low and high dosages with or without HCT. The intended lowering of blood pressure is effective and well tolerable also repeatedly during the 48-h, therapy-free interval (missed dose trial) which corresponds to a frequent omission of the daily tablet dose and thus well reflects the daily practice in antihypertensive therapeutic regimens.     

Mechanistic Model for Blood Pressure and Heart Rate Changes Produced by Telmisartan in Human Beings

Telmisartan, an angiotensin receptor blocker (ARB), is indicated for the treatment of essential hypertension. This study aimed to develop a mechanistic model of telmisartan drug effect in human beings using non‐invasive markers. Data were acquired from a previous study where telmisartan 80 mg was given once daily for 6 days. Systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) were measured before dosing for days 1–5 and serially after the last dose. Mean arterial pressure (MAP) and pulse pressure (PP) were calculated from SBP and DBP. Relationships between MAP, PP, HR and total peripheral resistance (TPR) were developed. Circadian variation was incorporated into PP and HR, and TPR was assumed to adjust itself in response to changes in PP and HR based on baroreflex mechanism. Drug effects were then described as lowering the set point of MAP through TPR with a physiological feedback effect stimulating HR and PP. Drug concentrations were described by a two‐compartment disposition model with first‐order absorption and lag time, and first‐order elimination. Circadian variation was described by cosine functions, having periods of 12 and 24 hr. A log‐linear model was used to describe drug effect, with estimated drug effect parameter of 0.051/hr. Estimated fractional turnover rate of PP, HR and TPR was 11.2 hr. The model successfully described the time courses of these cardiovascular variables. This work demonstrated the feasibility of using non‐invasive cardiovascular measurements to derive a mechanistic model for telmisartan in human beings. The model may be suitable for other ARBs.     

通过动态血压监测观察福辛普利的降压作用

目的：以动态血压监测手段评价轻至中度原发性高血压患者服用福辛普利的降压作用。方法：患者每天服福辛普利１０ｍｇ,４周为一疗程。结果：福辛普利对收缩压和舒张压及负荷值均有明显降低作用,昼夜降压效果相似,不影响原有昼夜节律,降压作用的谷峰比值,收空压和舒张压分别为６０．７％和６７．５％。副反应轻微。结论：福辛普利是安全有效且服用方便的降压药物。     

氨氯地平联合阿托伐他汀治疗原发性高血压的疗效观察

目的:观察氨氯地平联合阿托伐他汀治疗原发性高血压的临床疗效。方法:104例原发性高血压患者随机分为2组,每组52例。观察组采用氨氯地平联合阿托伐他汀治疗,对照组仅采用氨氯地平治疗,观察比较2组的临床疗效及对血脂、血压、脉压的影响。结果:观察组的总有效率(92.3%)明显高于对照组(76.9%),2组比较差异有统计学意义(P<0.05)。观察组治疗后总胆固醇、甘油三酯水平均明显低于同期对照组(P<0.05),观察组与治疗前比较差异有统计学意义。2组治疗后收缩压、舒张压及脉压明显下降,与治疗前比较差异均有统计学意义(P<0.05);并且,观察组治疗后收缩压、舒张压及脉压均明显低于同期对照组,2组比较差异有统计学意义(P<0.05)。结论:在氨氯地平基础上加用阿托伐他汀能够明显提高治疗原发性高血压的临床疗效,降低患者血脂水平,且降低血压和脉压效果更为明显,二者联合应用具有良好的协同作用。     

不同机制降压药物治疗中青年单纯性舒张期高血压的疗效

目的探讨不同机制降压药物乐卡地平、比索洛尔、替米沙坦在初诊的单纯舒张期高血压患者中的短期疗效。方法纳入初发单纯舒张期高血压患者122例,平均年龄(37.7±5.1)岁,随机分为3个药物治疗组:1乐卡地平组(n=40):予乐卡地平10 mg/d;2比索洛尔组(n=38):予比索洛尔5 mg/d;3替米沙坦组(n=44):予替米沙坦40 mg/d。比较干预4周后的治疗效果差异。结果治疗4周后,所有患者舒张压均有明显下降(P<0.05)。乐卡地平组:舒张压平均降低(8.3±2.0)mmHg,95%可信区间7.5~9.1 mmHg;比索洛尔组:舒张压平均降低(6.8±2.1)mmHg,95%可信区间5.9~7.7 mmHg;替米沙坦组:舒张压平均降低(7.9±1.8)mmHg,95%可信区间7.2~8.6 mmHg。其中乐卡地平及替米沙坦组降压幅度相当(P=0.193),均强于比索洛尔组(P<0.05)。乐卡地平组治疗后,心率较治疗前升高明显(P<0.05),比索洛尔可有效控制患者心率(P<0.05),替米沙坦治疗后,患者心率有所降低(P<0.05)。结论乐卡地平可有效控制单纯舒张期高血压患者的舒张压,但可引起反射性心率增快,必要时可与比索洛尔联合用药;替米沙坦降压效果明确,可有效抑制肾素血管紧张素醛固酮(RASS)系统活性,可作为单纯舒张期高血压患者单药治疗的首选。     

替米沙坦对原发性高血压左心室肥厚的逆转作用观察

目的观察替米沙坦对原发性高血压（EH）伴左心室肥厚（LVH）患者的逆转作用。方法选择EH伴LVH患者62例,均予替米沙坦口服治疗。观察治疗前后患者收缩压（SBP）、舒张压（DBP）、心率（HR）及左室舒张末期室间隔厚度（IVST）、左室后壁厚度（LVPET）、舒张末期左室内径（LVDd）和左室重量指数（LVMI）。结果治疗后患者SBP、DBP均低于治疗前,差异均有统计学意义（P〈0.05）。治疗后IVSH、LVPWT、LVDd、LVMI均低于治疗前,差异均有统计学意义（P〈0.05）。结论替米沙坦能有效地控制血压,且对EH伴LVH有逆转作用,值得临床推广应用。