Interaction between isoprenaline and aminophylline in asthma

Campbell, I. A., Middleton, W. G., McHardy, G. J. R., Shotter, Margaret V., McKenzie, R., and Kay, A. B. (1977).Thorax, 32, 424-428. Interaction between isoprenaline and aminophylline in asthma. Using a factorially designed study, 38 patients with bronchial asthma received a single dose of either isoprenaline by inhalation (9), aminophylline intravenously (10), isoprenaline and aminophylline (11), or placebo (8). The maximum expiratory flow (V max), the maximum expiratory flow at 50% of vital capacity (V max50), and the concentrations of plasma cyclic AMP were measured at time intervals up to two hours. The combination of isoprenaline and aminophylline acted synergistically in terms of the percent increase in V max50. However, this was statistically significant only at 20 minutes. Plasma cyclic AMP concentration rose with a similar time course of response to the changes in small airways. The elevations in plasma cyclic AMP observed with the drug combination were higher than those for the individual drugs at 10, 20, 30, and 60 minutes but these differences were not statistically significant. These observations support the concept that changes in bronchial smooth muscle tone are mediated by concentrations of cyclic nucleotides and that combinations of isoprenaline and aminophylline, rather than the administration of each drug separately, may have therapeutic advantages in the treatment of bronchial asthma.