Wolfe J D, Tashkin D P, Calvarese B, Simmons M
N Engl J Med. 1978 Feb 16;298(7):363-7. doi: 10.1056/NEJM197802162980703.
In 17 patients with moderate to severe asthma, we compared acute bronchodilator effects of the following drugs or drug combinations using a double-blind crossover design: terbutaline, 5; aminophyline 400; terbutaline, 5, plus aminophyline, 400; terbutaline, 2.5; aminophylline, 200; terbutaline, 2.5, plus aminophyline, 200 mg; and placebo. The higher doses of terbutaline and aminophylline alone produced comparable bronchodilation and similarly frequent adverse side effects; low doses of each drug also had comparable effects. The high-dose combination produced significantly (P less than 0.05) greater bronchodilatation than either drug alone. The low dose combination had bronchodilator effects comparable to those produced by the higher dose of either drug alone. These findings suggest therapeutic advantages in combining high doses of theophylline and an oral beta adrenergic agonist (terbutaline) in asthma not well controlled on high doses of either drug alone and in combining these drugs in lower doses in patients experiencing intolerable side effects from a high dose of either drug.
在17例中重度哮喘患者中,我们采用双盲交叉设计比较了以下药物或药物组合的急性支气管扩张作用:特布他林5mg、氨茶碱400mg、特布他林5mg加氨茶碱400mg、特布他林2.5mg、氨茶碱200mg、特布他林2.5mg加氨茶碱200mg以及安慰剂。单独使用较高剂量的特布他林和氨茶碱产生的支气管扩张作用相当,且不良反应发生频率相似;每种药物的低剂量也有类似效果。高剂量组合产生的支气管扩张作用明显(P<0.05)强于单独使用任何一种药物。低剂量组合的支气管扩张作用与单独使用较高剂量的任何一种药物相当。这些发现表明,对于单独使用高剂量药物无法良好控制的哮喘患者,将高剂量的茶碱与口服β肾上腺素能激动剂(特布他林)联合使用具有治疗优势;对于因高剂量的任何一种药物出现难以耐受副作用的患者,将这些药物低剂量联合使用也具有治疗优势。