Reeves R A, Boer W H, DeLeve L, Leenen F H
Department of Medicine, Toronto Western Hospital, Ontario, Canada.
Clin Pharmacol Ther. 1989 Sep;46(3):279-90. doi: 10.1038/clpt.1989.139.
We determined whether the beta-blockade disappearance rate would determine the degree of subsequent transient beta-adrenoceptor hyperresponsiveness after abrupt withdrawal of a beta-adrenoceptor drug. In a single-blind randomized study, 10 healthy men took a placebo for 1 week and then took nadolol one time a day (t1/2, 18 to 24 hours) or propranolol three times a day (t1/2, 4 to 6 hours) in doses that were increased weekly for 4 weeks to reach 240 mg per day. beta-Receptor responsiveness was assessed before and repeatedly after abrupt drug withdrawal by infusion of isoproterenol and epinephrine and by ergometer exercise. In the 13 days after drug discontinuation, peak beta-receptor sensitivity correlated (p less than 0.05) with the disappearance rate of beta-blockade as assessed by heart rate responses to isoproterenol (r = 0.68) and to submaximal exercise (r = 0.62) and by diastolic blood pressure responses to isoproterenol (r = 0.86) and epinephrine (r = 0.86). Plasma catecholamine levels and renin activity showed no overshoot. beta-Blockers with long plasma t1/2 values may prevent beta-blocker withdrawal syndromes by means of "self-tapering."
我们确定β受体阻滞剂的消失率是否会决定β肾上腺素能药物突然撤药后随后出现的短暂性β肾上腺素能受体高反应性的程度。在一项单盲随机研究中，10名健康男性服用安慰剂1周，然后每天服用一次纳多洛尔（半衰期为18至24小时）或每天服用三次普萘洛尔（半衰期为4至6小时），剂量每周增加，持续4周，达到每天240毫克。在突然停药前和停药后通过输注异丙肾上腺素和肾上腺素以及进行测力计运动反复评估β受体反应性。在停药后的13天内，通过异丙肾上腺素（r = 0.68）和次极量运动（r = 0.62）引起的心率反应以及异丙肾上腺素（r = 0.86）和肾上腺素（r = 0.86）引起的舒张压反应评估的β受体峰值敏感性与β受体阻滞剂的消失率相关（p < 0.05）。血浆儿茶酚胺水平和肾素活性未出现过冲现象。血浆半衰期长的β受体阻滞剂可能通过“自我逐渐减量”来预防β受体阻滞剂撤药综合征。
