Bremner P, Burgess C, Beasley R, Woodman K, Marshall S, Crane J, Pearce N
Department of Medicine, Wellington School of Medicine, New Zealand.
Respir Med. 1992 Sep;86(5):419-23. doi: 10.1016/s0954-6111(06)80009-0.
The pulmonary and extrapulmonary effects of two doses of nebulized fenoterol (5 mg) salbutamol (5 mg) and ipratropium bromide (0.5 mg) at 60 min intervals were compared in nine patients with asthma in a double-blind, randomized study. Measurements of heart rate, blood pressure, electromechanical systole (QS2I), QTc interval, FEV1 and plasma potassium were made at baseline and at 15, 30 and 60 min after each nebulization. Both beta-agonists caused significantly greater inotropic (QS2I), chronotropic (HR), electrocardiographic (QTc) and hypokalaemic effects than ipratropium bromide (IB), with fenoterol being more potent than salbutamol. Fenoterol had no greater effect on FEV1 than salbutamol although both were superior to IB. Only the first four subjects had two doses as originally intended, because the second administration of fenoterol resulted in marked cardiovascular effects and hypokalaemia. The observed differences in extrapulmonary effects between fenoterol and salbutamol provide a plausible group of mechanisms which may explain the increased risk of death associated with fenoterol in severe asthmatics.
在一项双盲随机研究中,对9例哮喘患者每隔60分钟雾化吸入两剂非诺特罗(5毫克)、沙丁胺醇(5毫克)和异丙托溴铵(0.5毫克)后的肺部和肺外效应进行了比较。在每次雾化前及雾化后15、30和60分钟测量心率、血压、机电收缩期(QS2I)、QTc间期、第一秒用力呼气量(FEV1)和血浆钾。两种β受体激动剂引起的变力性(QS2I)、变时性(HR)、心电图(QTc)和低钾血症效应均显著大于异丙托溴铵(IB),非诺特罗比沙丁胺醇更有效。非诺特罗对FEV1的作用并不比沙丁胺醇更强,尽管两者均优于IB。只有前4名受试者按原计划接受了两剂药物,因为再次给予非诺特罗导致了明显的心血管效应和低钾血症。非诺特罗和沙丁胺醇在肺外效应上观察到的差异提供了一组合理的机制,这可能解释了重度哮喘患者中与非诺特罗相关的死亡风险增加的原因。