Rangno R E, Langlois S
Am Heart J. 1982 Aug;104(2 Pt 2):473-8. doi: 10.1016/0002-8703(82)90142-9.
Three groups of hypertensive patients were studied after they had received one of the three pharmacologically different beta blockers for at least 1 month: pindolol, 10 mg twice a day (n = 7), propranolol median dose, 80 mg three times a day (n = 9), or metoprolol, 150 mg (twice a day (n = 8). After abrupt withdrawal of drug and replacement with placebo, we measured the following on day 0 and approximately every 2 days up to 3 weeks; beta-adrenergic sensitivity (BAS) by the chronotropic dose of isoproterenol to increase heart rate by 25 bpm (CD25), resting heart rate and blood pressure, and symptoms. All values are medians. On day 0, beta blockade was evident by increased CD25 values of 618 micrograms for pindolol, 57 micrograms for propranolol, and 10 micrograms for metoprolol as compared to 2.8, 2.4, and 3.0 microgram, respectively, at days 14 to 21, which were considered the ultimate baseline. After pindolol on day 0, the CD25 slowly decreased to, but never below, baseline by days 8 to 21. In contrast, after propranolol on day 0, the CD25 decreased significantly two- to fivefold below baseline from days 4 to 14 (BAS) and after metoprolol two- to threefold below baseline from days 2 to 8. After pindolol, heart rate and blood pressure gradually returned to, but not above, ultimate baseline. In contrast, during the period of BAS there was a significant overshoot of heart rate in eight patients after metoprolol (day 0 = 61, peak = 88, baseline = 74) but not after propranolol, while a significant overshoot of blood pressure occurred in six of nine patients after propranolol (day 0 = 140/87, peak = 157/95, baseline = 140/89) but not after metoprolol. Withdrawal symptoms of headache, palpitations, and tremor occurred in one of seven patients after pindolol, six of nine after propranolol, and three of eight after metoprolol. The degree and duration of beta blockade appeared related to drug potency. Withdrawal phenomena occurred after propranolol and metoprolol but not after pindolol.
对三组高血压患者进行了研究，他们接受了三种药理作用不同的β受体阻滞剂中的一种，且用药时间至少为1个月：吲哚洛尔，每日两次，每次10毫克（n = 7）；普萘洛尔，中位剂量，每日三次，每次80毫克（n = 9）；或美托洛尔，每日两次，每次150毫克（n = 8）。在突然停药并换用安慰剂后，我们在第0天以及之后直至3周的时间里，大约每2天测量一次以下指标：通过异丙肾上腺素使心率增加25次/分钟的变时剂量（CD25）来测定β肾上腺素能敏感性（BAS）、静息心率、血压以及症状。所有数值均为中位数。在第0天，与分别在第14至21天被视为最终基线时的2.8微克、2.4微克和3.0微克相比，吲哚洛尔的CD25值增加到618微克，普萘洛尔为57微克，美托洛尔为10微克，表明β受体阻滞明显。在第0天给予吲哚洛尔后，CD25在第8至21天缓慢下降至基线水平，但从未低于基线。相比之下，在第0天给予普萘洛尔后，CD25在第4至14天显著下降至基线以下两至五倍（BAS）；给予美托洛尔后，在第2至8天下降至基线以下两至三倍。给予吲哚洛尔后，心率和血压逐渐恢复至最终基线水平，但未超过该水平。相比之下，在BAS期间，美托洛尔组有8名患者心率出现显著的过冲现象（第0天 = 61，峰值 = 88，基线 = 74），而普萘洛尔组未出现；普萘洛尔组9名患者中有6名血压出现显著过冲现象（第0天 = 140/87，峰值 = 157/95，基线 = 140/89），而美托洛尔组未出现。吲哚洛尔组7名患者中有1名出现头痛、心悸和震颤等撤药症状，普萘洛尔组9名中有6名，美托洛尔组8名中有3名。β受体阻滞的程度和持续时间似乎与药物效力有关。普萘洛尔和美托洛尔出现了撤药现象，而吲哚洛尔未出现。
