Interaction of orally administered metoprolol,practolol and propranolol with isoprenaline in asthmatics

Summary In a single-blind study eight patients with asthma received on five different days, in randomized order, doses of: propranolol 40 mg, metoprolol 50 mg and 100 mg (a new selective beta₁-blocking agent with no intrinsic activity), practolol 200 mg or placebo. The beta₁-blocking potency of the selective drugs at these dose levels was higher than or equal to that of propranolol. The effects on heart rate, blood pressure, ventilatory capacity (FEV₁) and skeletal muscle tremor were studied at rest and during infusion of increasing doses of isoprenaline. There was a slight decrease in FEV₁ after propranolol and both doses of metoprolol. After the placebo, isoprenaline produced a dose-dependent increase in heart rate, systolic blood pressure, FEV₁ and tremor, and lowered the diastolic blood pressure. Propranolol almost completely blocked the effects of all doses of isoprenaline on heart rate, FEV₁ and tremor, and, to a lesser extent, any change in systolic and diastolic pressure. The two doses of metoprolol and practolol did not inhibit the effect of isoprenaline on FEV₁. The effect of metoprolol and practolol on the isoprenaline-induced increase of heart rate indicated their selectivity for beta₁-receptors. The increase in tremor during infusion of isoprenaline was blocked by propranolol, but not by the selective beta₁-blockers, which implies that the induction of tremor was a beta₂-effect. The effect of isoprenaline on FEV₁ was not inhibited by selective beta₁-blocking agents, and so, when combined with beta₂-stimulators, they may be given to asthmatic patients.     

美托洛尔对老年患者心功能及心率变异性的影响

目的评价美托洛尔对老年患者心功能及心率变异性(HRV)的影响。方法心血管病老年患者426例,年龄≥70岁,口服美托洛尔治疗12个月。观察治疗前、治疗12个月后BP、HR、HRV(340例窦性心律患者)、左室收缩末期容积(LVESV)和舒张末期容积(LVEDV)、左室射血分数(LVEF)和心排血量(CO)的变化。结果与治疗前比较,治疗后BP、HR明显降低(P<0.05),LVEDV及LVESV明显降低[(173.22±45.42)ml vs.(158.55±40.34)ml和(150.34±54.14)mlvs.(134.65±44.02)ml](P<0.05)],而LVEF和CO明显增加[(56.16±3.26)%vs.(60.25±4.05)%和(4.2±1.2)L vs.(5.4±1.9)L](P<0.05)]。HRV各参数均较治疗前明显升高。药物相关的不良反应无明显增加。结论对老年患者,美托洛尔降低心率和血压的同时,明显改善HRV及心功能。     

Influence of propranolol and pindolol on the haemodynamic effects of papaverine,isoprenaline and noradrenaline in hypertensive patients

Summary The influence of two -adrenoceptor antagonists, propranolol and pindolol, on the haemodynamic effects of papaverine, isoprenaline and noradrenaline was investigated in 9 male patients with first degree essential hypertension. Propranolol and pindolol were given according to a doubleblind, crossover scheme. Heart rate and blood pressure were measured before and after each treatment. Propranolol 670 µg/kg i. v. reduced the supine and standing systolic blood pressures by 2.3% and 1.6%, respectively. Similarly, the intravenous administration of pindolol 35 µg/kg reduced supine and standing systolic blood pressure by 5.5% and 8.3% respectively (clinically insignificant). Neither drug affected diastolic blood pressure. Following propranolol, there were moderate reductions in supine and standing heart rates, respectively by 24% and 20% (p<0.001). Similarly, but to a lesser extent, pindolol reduced supine and standing heart rate by 12% and 17% (p<0.001). The effects of papaverine, which, at 1.5 mg/kg i. v. reduced systolic blood pressure by 5–10% and increased heart rate by 8–15%, were not significantly influenced by the -blockers. The blood pressure and heart rate responses to isoprenaline, on the other hand, were attenuated or inhibited by both -blockers. While the -blockers inhibited the -adrenoceptor component of noradrenaline, the pressor component of noradrenaline, which is mediated through the -adrenoceptors, was not influenced by propranolol, but was inhibited after pindolol. It is concluded that pindolol differs qualitatively from propranolol in that it inhibited both the -and -adrenoceptor effects of noradrenaline.Abbreviations BP blood pressure - ECG electrocardiogram - HR heart rate - ISA intrinsic sympathomimetic activity     

The pharmacodynamic and pharmacokinetic interaction of flecainide acetate with propranolol: Effects on cardiac function and drug clearance

Summary The effect of aluminum phosphate on the bioavailability of ranitidine has been investigated in 10 young, healthy volunteers. Following a random cross over design, each subject took at a 1 week interval 150 mg ranitidine alone or with 11 g aluminum phosphate. Plasma and urine ranitidine levels were measured by HPLC. The antacid reduced both the maximum plasma ranitidine concentration by 40% and the area under the curve by 30%. Elimination of ranitidine was not changed. The results indicate that aluminum phosphate significantly diminished the bioavailability of ranitidine.     

左西孟旦联合美托洛尔对老年慢性心力衰竭患者心功能、N端脑钠肽前体和心室重构的影响

目的 研究左西孟旦联合美托洛尔对老年慢性心力衰竭患者心功能、N端脑钠肽前体水平和心室重构的影响。方法 选取2015年1月-2017年12月新疆兵团第一师医院诊治的老年慢性心力衰竭患者81例,按治疗方法分为对照组41例、观察组40例。对照组口服美托洛尔片治疗,观察组联合给予左西孟旦注射液治疗。比较两组的治疗有效率,心功能指标以及N端脑钠肽前体水平。结果 观察组老年慢性心力衰竭患者的总有效率为92.50%,明显高于对照组的75.61%,差异有统计学意义（P<0.05）。治疗后两组患者的左心室射血分数、左心室舒张末期内径、左心室后壁厚度均显著改善,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组更明显,组间比较差异有统计学意义（P<0.05）。两组治疗后的N端脑钠肽前体水平均明显降低,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组更为明显,组间比较差异有统计学意义（P<0.05）。结论 左西孟旦联合美托洛尔可以有效改善老年慢性心力衰竭患者的心功能,降低N端脑钠肽前体水平,抑制心室重构,且具有较高的安全性。     

血灵侧脑室注射对大鼠动脉血压和心率的影响

目的：血灵是降血压中药制剂。本实验探讨血灵对心血管中枢的作用及其机理。方法：将药物微量地注射入麻醉大鼠侧脑室,观察注药后６０ｍｉｎ内血压和心率的变化。结果：（１）侧脑室注射血灵（１０ｍｇ／２０ｕｌ）引起动脉血压明显升高,２５ｍｉｎ时达到峰值,增幅为２６．５９％;心率增加,增幅为１５．７６％,侧脑室注射相同窖的ＮＳ。血压和心率无明显影响。（２）血压升高与侧脑室注射血灵的剂量呈明显的剂量－效应关系。（     

美托洛尔控制不停跳冠状动脉搭桥术中心率的临床研究

目的探讨美托洛尔控制冠状动脉搭桥术中心率的效果及安全性。方法回顾性分析4｜D例不停跳冠状动脉搭桥术患者的临床资料。结果40例患者静脉注射美托洛尔1min后HR开始减慢,3min后即显著下降至（69．2±10．8）~／min,与治疗前[（85．1-i-13．5）次／min]差异有统计学意义（t=3．94,P〈0．01）,10min时降到最低值（63．0±6．2）次／min,30min后缓慢上升,但仍未超过治疗前水平;术中平均动脉压相对稳定,治疗后3min、5min、10min、30min与治疗前差异无统计学意义（F=0．56,P〉0．05）。结论美托洛尔能有效控制不停跳冠状动脉搭桥术中心率变化,且不会导致血流动力学变化。     

Heart rate and blood pressure responses to intravenous boluses of isoprenaline in the presence of propranolol, practolol and atropine.

Six healthy subjects were studied on two occasions. Graded bolus injections of isoprenaline sulphate were given intravenously and control dose-response curves were drawn for the changes in heart rate and blood pressure. In a random order each subject received an intravenous infusion of either propranolol or practolol and further dose-response curves were constructed PRE- and POST-atropine (0.04 mg/kg). Exercise tachycardia was reduced 26.1 +/- 2.7% by propranolol and this was not significantly different from the reduction by practolol (21.2 +/- 1.9%). Propranolol attenuated the isoprenaline tachycardia (dose ratio 43.7) and after atropinisation the dose ratio was not significantly altered (41.1). Practolol also attenuated the isoprenaline tachycardia (dose ratio 4.4) but after atropinisation the dose ratio was significantly increased to 8.8, though this remained significantly less than the dose ratio for propranolol. At a heart rate increase of 25 beats/min, the isoprenaline-induced control fall in mean blood pressure was 9-11 mm Hg. After propranolol administration this fall was converted to a small increase of + 2.3 +/- 1.3 mm Hg. Following practolol, however, the mean blood pressure reduction was 19.7 +/- 2.9 mm Hg. Practolol did not significantly block the isoprenaline-induced fall in diastolic pressure. The difference in potency of propranolol and practolol, demonstrated by their effect on isoprenaline induced tachycardia at doses shown to have equal effects on exercise tachycardia, is contributed to but not fully explained by the reflex withdrawal of cardiac vagal tone which occurs with cardioselective but not non-selective antagonists.     

Effects of oral salbutamol and pirbuterol on FEV1, heart rate and blood pressure in asthmatics

1 In a double-blind trial the effects on ventilatory function (FEV₁), heart rate and blood pressure of oral pirbuterol and oral salbutamol in various single doses were studied in ten patients with chronic asthma.

2 Pirbuterol (15 mg) and salbutamol (4 mg) produced equal peak levels of bronchodilatation.

3 There was no significant difference in the mean rise in heart rates caused by the two drugs, and no other significant side-effects were noted.

     

Impact of metoprolol treatment on cardiac function and exercise tolerance in heart failure patients with neuropsychiatric disorders

Objective: To investigate the impact of neuropsychiatric disorders on the effect of metoprolol on cardiac and motor function in chronic heart failure (CHF) patients.

Methods: From February 2013 to April 2016, CHF patients with clinical mental disorders received metoprolol (23.75 or 47.5?mg, once daily, orally) at the Second Affiliated Hospital of Kunming Medical University. Mental status was confirmed by means of the Hospital Anxiety and Depression Scale (HADS) and the Copenhagen Burnout Inventory (CBI) scale. Cardiac function parameters such as systolic blood pressure (SBP), ejection fraction (EF) and cardiac index (CI) as well as motor function including the 6 meter walk test (6MWT) and the Veteran’s Specific Activity Questionnaire (VSAQ) were assessed as primary outcomes of the study.

Results: A total of 154 patients (median age, 66.39 years; men, n?=?101) were allocated into eight groups based on their mental status. There were no significant differences in heart rate (HR) or SBP control achieved by metoprolol in any groups compared with the control (patients with normal mental status). Furthermore, biphasic ejection fraction (EF) changes were observed in all the groups with a decrease in the first month and increase from the sixth month. However, this increase was significantly lower (p?Conclusion: Depressive and high burnout symptoms, but not anxiety, lower the improvement of cardiac and motor function by metoprolol treatment in CHF.     

Changes in heart rate and forearm blood flow following intravenous boluses of isoprenaline in the presence of practolol and propranolol

1 Increases in heart rate and forearm blood flow following graded intravenous bolus injections of isoprenaline sulphate, were measured in a double-blind randomised study of six subjects who received either placebo, practolol 50 mg, practolol 200 mg, propranolol 10 mg or propranolol 40 mg. 2 Dose related increases in forearm blood flow were produced by the graded boluses of isoprenaline sulphate. 3 Practolol 50 mg attenuated the heart rate response to isoprenaline but did not significantly affect the changes in forearm blood flow. Practolol 200 mg further attenuated the heart rate responses but also decreased the forearm blood flow responses. 4 Propranolol 10 mg and propranolol 40 mg significantly attenuated both the heart rate and forearm blood flow responses. The effect on forearm blood flow tended to be greater than the effect on heart rate. 5 Practolol 200 mg had the same effect on heart rate responses as propranolol 10 mg but a significantly smaller effect on the forearm blood flow responses. 6 The measurement of forearm blood flow following intravenous bolus injections of isoprenaline provides useful information about the beta 2-adrenoceptor antagonism of propranolol and practolol. However, application of the technique may be limited by the magnitude of the heart rate response and by the short-lived nature of the increase in forearm blood flow.     

Effects of long-acting propranolol on blood pressure and heart rate in hypertensive Chinese.

In a double-blind, balanced and randomised study we used treadmill exercise to assess the effects of long-acting propranolol (LA propranolol) 160 or 320 mg or placebo, given once daily for 4 weeks, on heart rate (HR) and blood pressure (BP) in 15 Chinese subjects with mild primary hypertension (PHT). We used 24 h ECG monitoring to assess drug effects on HR. Another 18 patients were similarly assessed without exercise. Steady-state plasma propranolol concentrations after LA propranolol 160 and 320 mg were comparable to those after ordinary propranolol 80 and 160 mg daily measured in 11 and 12 separate patients. LA propranolol 160 and 320 mg reduced HR and BP before and during vigorous exercise. LA propranolol 160 and 320 mg reduced HR for 17.6 and 21.4 h of the day, and 320 mg significantly reduced the mean 24 h HR, and the mean maximum HR. The drug effects on BP and HR, and the average plasma propranolol levels after LA propranolol were similar to those reported in European subjects.     

Effects of beta-adrenergic blocking drugs on ventilatory function in asthmatics

Summary The effects on respiratory function have been compared of five different beta-blocking drugs injected intravenously in asthmatic patients. In all groups but one there was a decrease in FEV₁ and an increased nitrogen washout time. After practiolol, only two cases of increase of nitrogen washout time were observed without a fall in FEV₁. Thus practolol seems much safer than the other agents in patients prone to respiratory distress.     

The effect of metoprolol and practolol on lung function and blood pressure in hypertensive asthmatics

1 The effect of metoprolol, a new β₁-adrenoceptor blocking agent, was compared to practolol in the treatment of hypertension in seventeen asthmatics during concurrent optimum bronchodilator therapy with a selective β₂-adrenoceptor-stimulant.

2 The two β-adrenoceptor antagonists were given at two dose levels, practolol (200 mg and 400 mg) daily, and metoprolol (100 mg and 200 mg) daily, in a twice-daily dosage schedule, at 12 h intervals, for 17 days. The comparison was made double-blind and a crossover design was used. The drugs were given in randomized order. The study started with a run-in placebo period and there was a washout period on placebo between the treatment periods. Spirometry, blood pressures and heart rates were recorded in a standardized manner.

3 At the lower dose levels no influence on FEV₁ was noted, and no difference was found between the two active drugs. At the higher dose level FEV₁ was reduced by both β-adrenoceptor-blocking drugs. Four out of twelve patients given the higher dose experienced exacerbation of their asthma. The heart rate fell with both drugs and at both dose levels. During the placebo period a marked increase of heart rate was noted. The blood pressure fell at both dose levels compared to placebo, no difference being recorded between the two drugs.

4 Metoprolol and practolol are equally effective β₁-adrenoceptor blocking drugs. In this study it was found that metoprolol could be used in asthmatics who had indications for β-adrenoceptor blockade, provided that the total daily dose did not exceed 100 mg. Optimal bronchodilator treatment with a bronchoselective β-adrenoceptor agonist is an absolute prerequisite in order to avoid the risk of aggravation of asthma.

     

Effect of diltiazem on the pharmacokinetics of propranolol,metoprolol and atenolol

Summary The pharmacokinetic interaction between diltiazem and three -adrenoceptor blockers propranolol, metoprolol and atenolol was investigated in healthy volunteers given diltiazem 30 mg or placebo t.d.s. for 3 days, followed by a single dose of propranolol 20 mg, metoprolol 40 mg or atenolol 50 mg.The AUCs of propranolol and metoprolol were significantly increased after diltiazem and it significantly prolonged the elimination half-life of metoprolol. In contrast, it did not significantly affect the pharmacokinetics of atenolol. Propranolol significantly decreased the resting pulse rate after diltiazem pretreatment as compared to placebo.The results indicate that diltiazem impaired the clearance of propranolol and metoprolol, which are principally metabolized by an oxidative pathway, and that the kinetic interaction between diltiazem and propranolol may partly be related to the significant reduction in the pulse rate produced by the latter.     

美托洛尔治疗舒张期高血压对血糖的影响

目的 探讨美托洛尔治疗舒张期高血压对血糖的影响.方法 选择120例舒张期高血压患者,随机分为研究组与对照组,每组各60例,研究组给予美托洛尔,对照组给予非洛地平,疗程12个月,治疗中定期检测和比较血糖、血压情况.结果 两组治疗后舒张压均较治疗前降低(均P ＜0.05),但两组间治疗前后舒张压差异无统计学意义(P＞0.05).两组治疗1、3、6个月时空腹血糖(GLU)、餐后2h血糖(P2hPG)与治疗前无明显差异,但研究组治疗12个月后GLU、P2hPG[分别为(6.23±0.89)、(7.46±0.71) mmol/L]较治疗前[分别为(4.97±0.52)、(5.21±0.69) mmol/L]及同期对照组[(5.13±0.48)、(5.16±0.67) mmoL/L]均高(均P ＜0.05).结论 美托洛尔治疗舒张期高血压效果较好,长期用药(1年或以上)对血糖有一定升高作用,但未发现其他不良反应,安全性尚好.     

美托洛尔联合芪苈强心胶囊治疗慢性心力衰竭的临床疗效及其对心功能的影响

目的 探讨美托洛尔联合芪苈强心胶囊治疗慢性心力衰竭的临床疗效及其对心功能的影响.方法 选取武威市中医院2017-2019年收治的慢性心力衰竭患者82例,按照随机数字表法分为对照组与观察组,各41例.对照组予以美托洛尔治疗,观察组在对照组基础上联合芪苈强心胶囊治疗.2组均连续治疗90 d.比较2组临床疗效,治疗前后心功能...     

Effects of intravenous infusion of doxorubicin on blood chemistry, blood pressure and heart rate in rabbits

The effects of a 1 h continuous infusion of doxorubicin (12.5 mg kg-1, 200 mg M-2) on blood chemistry was examined in rabbits over a 6-h period. Plasma glucose levels remained unchanged while insulin levels were significantly decreased to 39, 45 and 61% of the zero time value (12.8 +/- 2.9 ng ml-1) at 30, 60 and 120 min, respectively, after starting the drug infusion. Plasma cortisol levels were increased to 141, 140 and 131% of the initial zero time value (12.3 +/- 2.2 ng ml-1) at 120, 240 and 360 min, respectively. Doxorubicin had no effect on plasma electrolytes, osmolality and urea nitrogen but significantly increased plasma creatinine over the corresponding control value (2.2 +/- 0.8 micrograms ml-1 to 4.9 +/- 0.7 micrograms ml-1) at 120 min and the level remained elevated for the remaining period of the study. Systolic and diastolic pressure, and heart rate were also depressed at 240 and 360 min. The data collected in the present study indicate that the doxorubicin infusion might have a direct effect on beta cells in the pancreas as well as muscle tissue. Changes in cortisol, blood pressure and heart rate appear to be secondary to other effects produced by doxorubicin.     

Effects and plasma levels of propranolol and metoprolol in hyperthyroid patients

Summary The effects and plasma concentrations of different doses of propranolol and metoprolol were studied in 34 hyperthyroid patients. The initial daily doses were propranolol 160 mg or metoprolol 200 mg. If the resting heart rate remained above 75 beats per min after treatment for 4–7 days, the dose was increased and the patient re-examined after a further 4–7 days. Propranolol (n=17) caused a reduced heart rate, a decrease in serum 3,3,5-triiodothyronine (T3) and an increase in serum 3,3,5-triiodothyronine (reverse T3, rT3). In 10 patients, there was no change in T3 or rT3 until the daily dose of propranolol had been increased to 240 or 320 mg. The plasma level of propranolol was significantly correlated with the decrease in T3 and the increase in rT3. Metoprolol (n=17) caused a reduction in heart rate similar to that following propranolol. However, serum T3 was only slightly reduced even after an increase in dose to 300 or 400 mg, and serum rT3 was not altered. Metoprolol concentrations were not significantly correlated with the fall in T3. It appears that the influence of-blockers on T4 conversion is of little importance for the clinical improvement in hyperthyroid patients, and rather it is a consequence of ₁-adrenergic blockade interfering with the effect of T3. In addition, the findings support the assumption that therapeutic failure with-blockers in hyperthyroidism may be due to suboptimal treatment, and that individualized dosage is necessary.     

美托洛尔、苯那普利、拜新同片对原发性高血压患者心率变异性的影响

目的　探讨美托洛尔、苯那普利、拜新同片对原发性高血压患者心率变异性的影响。方法　将 6 0例高血压患者随机分成三组 ,分别服用美托洛尔、苯那普利、拜新同片 ,治疗前与治疗后 4周做动态心电图监测并进行心率变异性分析。结果　服用美托洛尔、苯那普利组用药后时域指标中 SDNN,SDANN,SONN index均显著增高 (P<0 .0 1) ,频域指标中 L F成份明显下降 ,HF成份明显增加 ,L F/HF也明显下降 (P<0 .0 5或 <0 .0 1) ,而拜新同片在治疗后心率变异比较无显著意义 (P>0 .0 5 )。结论　美托洛尔、苯那普利在降压的同时 ,可改善原发性高血压患者的心率变异性 ,尤以美托洛尔组更为显著 ,而拜新同片在治疗前后则差异无显著性