Shapiro W, Park J, DiBianco R, Singh S N, Katz R J, Fletcher R
Chest. 1981 Oct;80(4):425-30. doi: 10.1378/chest.80.4.425.
Nadolol, a new nonselective beta 1 and beta 2 adrenergic blocking agent, has a plasma half-life of 17 to 23 hours. We studied 37 volunteers with stable angina pectoris who had five or more episodes of pain per week and who also had a 1 mm or greater ST segment depression 80 msec past the J point during a Bruce protocol treadmill test. An eight-week placebo controlled run-in period preceded double-blind randomization to nadolol administered once per day (17 patients) or identical appearing placebo for four weeks (20 patients), after which an exercise test was done. Diaries for pain episodes and nitroglycerin consumption were kept. Exercise tests were performed 24 hours after the last nadolol or placebo dose. Episodes of pain per week were reduced 59.8 percent after nadolol and 28.2 percent after placebo (P less than .01). Nitroglycerin consumption after nadolol was reduced 66.8 percent while after placebo it was reduced 36.2 percent (P less than .05). Resting and peak heart rates and peak rate-pressure products showed typical reductions due to beta-blockade 24 hours after nadolol compared with stability of these during placebo, all P less than .001. Exercise time after nadolol increased 42.2 percent, which was more than the 14.5 percent increase after placebo (P less than .05). Exercise work after nadolol increased 64.7 percent, greater than the 22 percent increase after placebo (P less than .05). Mean ST segment depression at end of exercise was little changed before and after treatment in both groups, reflecting consistency of effort. Improvement in symptoms and work capacity associated with nadolol significantly exceeded the placebo group responses. Unlike other available agents of this class, a single daily dose of nadolol produced therapeutically effective 24-hour beta-blockade in patients with disabling angina pectoris.
纳多洛尔是一种新型的非选择性β1和β2肾上腺素能阻滞剂,其血浆半衰期为17至23小时。我们研究了37名稳定型心绞痛志愿者,他们每周有五次或更多次疼痛发作,并且在布鲁斯方案跑步机试验中,J点后80毫秒处ST段压低1毫米或更多。在双盲随机分组接受每日一次的纳多洛尔治疗(17例患者)或外观相同的安慰剂治疗四周(20例患者)之前,有一个为期八周的安慰剂对照导入期,之后进行运动试验。记录疼痛发作和硝酸甘油消耗的日记。在最后一剂纳多洛尔或安慰剂后24小时进行运动试验。服用纳多洛尔后每周疼痛发作次数减少了59.8%,服用安慰剂后减少了28.2%(P<0.01)。服用纳多洛尔后硝酸甘油消耗量减少了66.8%,而服用安慰剂后减少了36.2%(P<0.05)。与安慰剂期间这些指标的稳定性相比,服用纳多洛尔24小时后,静息心率、峰值心率和峰值速率压力乘积因β受体阻滞剂作用出现典型下降,所有P<0.001。服用纳多洛尔后运动时间增加了42.2%,高于服用安慰剂后的14.5%的增加幅度(P<0.05)。服用纳多洛尔后运动功增加了64.7%,大于服用安慰剂后的22%的增加幅度(P<0.05)。两组运动结束时的平均ST段压低在治疗前后变化不大,反映了运动强度的一致性。与纳多洛尔相关的症状和工作能力改善显著超过安慰剂组的反应。与该类其他现有药物不同,每日一剂纳多洛尔在致残性心绞痛患者中产生了治疗有效的24小时β受体阻滞作用。