Waal-Manning H J
Clin Pharmacol Ther. 1979 Jan;25(1):8-18. doi: 10.1002/cpt19792518.
The object of this study was to establish whether cardioselectivity of atenolol confers any advantage over noncardioselective beta-blockade in the treatment of hypertension. A dose of atenolol was established on the basis of morning mean systolic blood pressure (mean of 5 readings) in 27 long-standing hypertensive patients previously controlled on one of three nonselective beta-blockers: propranolol, oxprenolol, or pindolol. Most patients were also taking a diuretic. A crossover trial was then conducted of atenolol and the previous nonselective beta-blocker, each drug being given for 8 wk in randomized order. Other drugs were kept constant. At the end of each 8-wk period a morning test of blood pressure and pulse rate was done, an 11:30 A.M. blood sample was taken for estimation of drug concentration, and spirometry was performed. During the eighth week a glucose tolerance test, fasting lipids, and other biochemical and hematologic estimations were done. On a separate occasion a late morning study was done on the response of blood pressure and pulse rate to three kinds of stress: bicycle ergometer, mental arithmetic, and handgrip. At dosage levels of atenolol giving a mean resting systolic blood pressure equal to that during nonselective beta-blockade, diastolic levels on atenolol tended to be lower at rest and during the mental and handgrip forms of stress. Serum creatinine levels on atenolol were lower than during nonselective beta-blockade. Anti-dioxyribonucleic acid (DNA) titers remained normal in all patients. There was no difference in lung function. There was little difference in glucose and insulin levels during glucose tolerance tests in these patients, half of whom were diabetic. There were no serious side effects but there were a few surprising ones such as vivid dreams in three and muscle cramps in one patient.
本研究的目的是确定在高血压治疗中,阿替洛尔的心脏选择性是否比非选择性β受体阻滞剂具有任何优势。根据27例长期高血压患者早晨平均收缩压(5次读数的平均值)确定阿替洛尔的剂量,这些患者之前使用三种非选择性β受体阻滞剂之一(普萘洛尔、氧烯洛尔或吲哚洛尔)控制血压。大多数患者还服用利尿剂。然后进行了阿替洛尔与之前使用的非选择性β受体阻滞剂的交叉试验,每种药物以随机顺序给药8周。其他药物保持不变。在每个8周疗程结束时,进行早晨血压和脉搏率测试,上午11:30采集血样以测定药物浓度,并进行肺活量测定。在第8周期间,进行葡萄糖耐量试验、空腹血脂以及其他生化和血液学评估。在另一个时间点,对上午晚些时候血压和脉搏率对三种应激(自行车测力计、心算和握力)的反应进行了研究。在给予阿替洛尔的剂量水平下,静息收缩压平均值与非选择性β受体阻滞剂治疗期间相等,阿替洛尔治疗时静息、精神应激和握力应激时的舒张压水平往往较低。阿替洛尔治疗时血清肌酐水平低于非选择性β受体阻滞剂治疗期间。所有患者的抗二氧核糖核酸(DNA)滴度均保持正常。肺功能无差异。这些患者中一半患有糖尿病,他们在葡萄糖耐量试验期间的血糖和胰岛素水平差异不大。没有严重的副作用,但有一些令人惊讶的副作用,如3例出现生动梦境,1例出现肌肉痉挛。