Metabolic aspects of maximal exercise performance after slow release metoprolol and after atenolol

Summary Maximal exercise performance by eight healthy male subjects was tested after one week of medication with slow-release metoprolol 200 mg/d (metoprolol-SR), atenolol 200 mg/d or placebo, in a double blind crossover trial. The maximal working capacity was significantly decreased after atenolol and metoprolol-SR. Plasma glucose and FFA concentrations during the exercise test did not change: either after placebo therapy or after beta-blockade. The anaerobic threshold did not change after beta-blockade, but the changes in lactate due to the exercise were less after beta-blockade. Neither beta-blocker affected the exercise-induced alteration in airway resistance. Both drugs caused a small but significant ventilatory depression at rest and at 75% of maximal exercise. It is concluded that the limiting factor in maximal exercise performance after ₁-adrenergic blockade does not lie in oxygen transport to the working muscles via ventilation and the circulation, but is most probably due to anaerobic metabolism.     

HPLC法测定复方阿替洛尔片中阿替洛尔与硝苯地平的含量

目的:采用高效液相色谱法考察并建立测定复方阿替洛尔片中阿替洛尔与硝苯地平含量的方法。方法:色谱柱为Phe-nomenex—ODS 3柱(250 mm×4.60 mm,5 μm),甲醇-水-磷酸盐缓冲溶液(取磷酸二氢钾6.8 g,加水1000 mL溶解后,用磷酸调pH至3.0)-庚烷磺酸钠适量摇匀(65:35:3:0.13 g=V:V:V:W)为流动相,流速为1.0 mL·min～1,检测波长为240 nm,进样量为10μL。结果:阿替洛尔的线性范围为10-250μg·mL-1(r=0.9999),硝苯地平的线性范围为4—100 μg·mL-1(r=1.0000),平均回收率分别为99.45％和99.51％。结论:本法精密度好,结果准确可靠,适用于该复方制剂的质量检验分析。     

阿替洛尔注射液对血管刺激、溶血和过敏的实验研究

目的 :观察阿替洛尔注射液血管刺激性和是否具有溶血、凝聚和过敏作用。方法 :兔耳缘静脉注射阿替洛尔 ,0 .2 5mg·kg- 1,qd× 3d ,停药 2 4h后做病理组织学检查 ,并与氯化钠注射液对照组比较 ;体外不同浓度的阿替洛尔注射液 0 .1～ 0 .5mL在 5mL兔红细胞氯化钠注射液中放置 0 .5～ 2 4h ,观察对兔红细胞悬液的溶血作用及有无红细胞凝聚作用 ;给豚鼠腹腔注射阿替洛尔 ,每只 0 .5mL ,qod× 3次 ,2wk和 3wk后分别再腹腔注射该药 ,每只2 .5mL- 1,然后观察 30min内是否出现过敏反应。结果 :阿替洛尔注射液对兔血管内皮没有损伤和刺激作用 ,与氯化钠注射液对照血管比较 ,两者无明显差异 ,对兔红细胞没有致溶血作用和凝聚作用 ,豚鼠未出现过敏反应。结论 :阿替洛尔注射液对用药血管没有刺激性反应 ,也无溶血及红细胞凝聚现象 ,对豚鼠无过敏反应。制剂有关安全性检测结果符合新药申报要求。     

Comparison of the metabolic effects of long-term treatment with pindolol or atenolol by hypertensive patients

Summary The effects of plasma lipids, blood glucose, and serum total cholesterol, LDL-cholesterol, VLDL-cholesterol, 6-month period were studied in 18 patients with essential hypertension.There were no significant changes in the concentration of serum total cholesterol. LDL-cholesterol, VLDL-cholesterol, and triglycerides during treatment periods with pindolol or atenolol, although there was a tendency to higher triglyceride levels during atenolol treatment.The serum HDL-cholesterol levels were significantly lower after 6 months of therapy with atenolol than before treatment, but HDL-cholesterol levels increased slightly during pindolol treatment. The ratio of HDL-cholesterol to total cholesterol decreased significantly during 6 months of treatment with atenolol.Fasting blood glucose concentrations did not change significantly during 6 months of treatment with pindolol or atenolol, but during oral glucose tolerance test, blood glucose values at 60 min were raised after pindolol therapy. Serum insulin levels during oral glucose tolerance test at 120 min were decreased after pindolol therapy, but no significant changes were found in C-peptide levels during treatment periods.     

Modest antihypertensive effect of epanolol,a beta1-selective receptor blocker with beta1 agonist activity: An acute and long-term hemodynamic study at rest and during exercise and double crossover comparison with atenolol on ambulatory blood pressure

Summary Beta-blockers with less cardiodepressive effect than traditional nonselective beta₁₊₂-blocking agents could be useful in the treatment of hypertension, provided the reduction in blood pressure was satisfactory. Epanolol, a selective beta₁-receptor blocker with intrinsic sympathomimetic activity, induced a fall in intraarterial pressure of 8% at rest sitting and 11% during 100 W bicycle exercise after the first dose of 200 mg in 12 patients with essential hypertension. Heart rate, stroke index, and cardiac index initially fell by 14%, 11%, and 23%, respectively. The total peripheral resistance index increased by 21% after 2 hours, and then reverted towards the pretreatment level. After 10 months of epanolol treatment (mean 300 mg/day), the reduction in arterial pressure was 5% at rest and 10% during exercise. Cardiac index and heart rate were still reduced 14–21%, while total peripheral resistance was unchanged or slightly increased (2–10%). Twenty-four hour ambulatory blood pressure was higher on epanolol (300 mg/day) than on atenolol (150 mg/day) treatment (137/97 vs. 128/91 mmHg). Thus, the achieved blood pressure reduction induced by epanolol was moderate, while other characteristics of beta-receptor blockade, in particular, the reduction of heart rate and cardiac output, were maintained. This suggests that the compound may be useful for other cardioavascular disorders, e.g., angina pectoris in patients without hypertension or cardiac arrhythmia.     

Captopril and atenolol are equally effective in retarding progression of diabetic nephropathy

Summary The progression of diabetic nephropathy can be positively influenced by maintaining a low blood pressure level. This has been shown in studies with conventional antihypertensive treatment as well as with ACE inhibitors. Whether the latter group of drugs is more effective remains to be proven and was the aim of our study. In a prospective randomized study we compared the effects of ACE inhibition and -blockade on retarding progression of renal function in IDDM patients with an early stage of overt diabetic nephropathy. Twenty-nine patients were studied for 2 years, 15 were randomized for treatment with captopril and 14 for atenolol. Every 6 weeks blood pressure and urinary albumin and total protein excretion were measured. GFR was measured every 6 months as ⁵¹Cr-EDTA clearance. Baseline values for blood pressure, renal function and albuminuria were identical in the two groups. The effect of both drugs on blood pressure was not significantly different. In the captopril-treated patients MAP before and after 2 years was 110±3 (SEM) and 100±2 mm Hg, respectively and in the atenolol-treated patients 105±2 vs 101±2 mm Hg. Both drugs reduced albuminuria and total proteinuria to the same extent. With captopril albuminuria decreased from 1549 (989–2399) to 851 (537–1380) mg/24 h and proteinuria from 2.5 (1.6–3.8) to 1.2 (0.8–1.8) g/24 h. With atenolol albuminuria decreased from 933 (603–1445) to 676 (437–1047) mg/ 24 h and proteinuria from 1.5 (1.0–2.4) to 0.9 (0.6–1.5) g/24 h. The rate of decline of GFR was similar with both treatments, on captopril –4.9±2.1 and on atenolol –3.7±1.6 ml · min^–1· year^–1. No major side effects with either drug were observed. We conclude that, in this 2-year study, captopril and atenolol are equally effective in retarding progression of diabetic nephropathy.Abbreviations IDDM insulin-dependent diabetes mellitus - ACE angiotensin converting enzyme - ECC endogenous creatinine clearance - MAP mean arterial pressure - GFR glomerular filtration rate     

Nisoldipine tablets once daily versus nifedipine capsules three times daily in patients with stable effort angina pectoris pretreated with atenolol

Summary Treatment with nisoldipine (2×10 mg tablets once daily) and nifedipine (2×10 mg capsules three times daily) in patients with severe, but stable effort angina pretreated with atenolol (100 mg once daily in 19 patients and 50 mg once daily in one patient) were compared for their effects on bicycle exercise tolerance and their adverse effects in a randomized 2×4 week, double-blind, double-dummy crossover study. All patients had multivessel disease, 16 patients had occlusion of at least one vessel, and eight patients had a history of myocardial infarction. Two patients left the study during the initial nisoldipine period, one because of aggravation of the angina and the other because of suspected allergic reaction. Addition of nifedipine to atenolol treatment significantly improved the variables measured for severity of angina, such as time of exercise until 1 mm and 2 mm ST-segment depression, total exercise time and total workload. In contrast, no such improvement was noted after the addition of nisoldipine to atenolol. However, nisoldipine resulted in a significant prolongation of the time to the initiation of chest discomfort, the maximum heart rate, and the double product.In atenolol-treated patients with severe effort angina pectoris, nifedipine 20 mg tid improved exercise capacity, while nisoldipine 20 mg once daily did not have a similar effect.     

Acute effects of alcohol, beta blockade, and their combination on left ventricular function and hemodynamics in normal man

Twenty-three healthy males, aged 23 to 62 years, were examinedby M-mode echocardiography and systolic time intervals for 3h after (1) ethanol 1 g/kg by mouth taken over 60 minutes; (2)atenolol 100 mg by mouth; (3) ethanol (1 g/kg) + atenolol (100mg). The peak mean blood ethanol (± s.e.) was 112 ±4mg/100 ml in test 1 and 104 ± 7 mg/100 ml in test 3.During increasing blood ethanol, heart rate (HR), systolic bloodpressure (BP), cardiac output (CO) and echocardiographic indicesof left ventricular (LV) function were significantly augmented,while total peripheral resistance (TPR) decreased. During decliningblood ethanol, systolic BP, L V end-diastolic and end-systolicdiameters, stroke volume (SV) and circumferential wall stresswere significantly reduced; echocardiographic indices of LVfunction were unaltered, but the pre-ejection period/LV ejectiontime ratio was increased, Atenolol decreased llR, systolic BP,SV, CO, and all estimates of LV function, but increased TPR.Ethanol + atenolol tended to cause smaller depressions in theindices of LV function than did atenolol alone, in spite ofsimilar plasma atenolol concentrations (n = 6). It is concludedthat ingestion of modest doses of ethanol evokes vasodilationand enhances LV function during increasing blood ethanol, andreduces LV preload and afterload during decreasing blood ethanolwithout impairing contractility. Social drinking and beta blockadeseem not to have any harmful acute combined effects on the heartand circulation, at least in normal subjects.     

LC-Q-TOF/MS技术鉴定阿替洛尔中氨基醇类有关物质

研究鉴定阿替洛尔中氨基醇类有关物质。阿替洛尔及其强制降解样品中的有关物质采用9-芴甲氧羰酰氯柱前衍生化,以Inertsil ODS-SP （250 mm×4.6 mm,5 μm）色谱柱,甲醇-乙酸铵缓冲液为流动相进行梯度洗脱分离,电喷雾正离子化-高分辨Q-TOF/MS测定这些有关物质衍生物的母离子及碎片离子的准确质量和元素组成,经光谱解析和合成路线分析鉴定各有关物质结构。所建立的方法,阿替洛尔及其氨基醇类有关物质均分离良好,共检测并鉴定出14个杂质峰,其中12个为有关物质,2个为衍生化反应副产物。建立的LC-MS方法可为阿替洛尔有关物质检查和质量控制提供参考依据。