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The Cardiovascular Effects of Inhaled Fenoterol Alone and during Treatment with Oral Theophylline

1989; Elsevier BV; Volume: 96; Issue: 6 Linguagem: Inglês

10.1378/chest.96.6.1317

1931-3543

Amber Flatt, Carl Burgess, Hugh H. Windom, Richard Beasley, G Purdie, Julian Crane,

Pharmacological Effects and Assays

We have investigated whether oral theophylline potentiated the cardiovascular effects of fenoterol administered by metered-dose inhaler. Eight healthy subjects were investigated on four occasions. On successive days (1 and 2), the subjects were given doses of 400μg, 600μg, and 800μg of fenoterol at 15-minute intervals (total dose, 1.8 mg) or matched placebo. Systolic time intervals, blood pressure, and the ECG were recorded at baseline and five minutes after each inhalation. Thereafter, the subjects were treated with slow-release theophylline for eight days. On days 9 and 10, the procedures on days 1 and 2 were repeated. The order of treatment was applied according to a crossover Latin-square design. The effects after theophylline alone were no different from placebo. Theophylline potentiated those hemodynamic effects of fenoterol due to enhanced cardiac sympathetic tone (mean±SE) as measured by a decrease in Q-S2I (–41.6±7.6 ms vs −27.3±5.9 ms; p=0.0004), an increase in systolic BP (23.5±2.8 mm Hg vs 9.0±5.3 mm Hg; p=0.00001), and an increase in heart rate (15.8±1.6 bpm vs 9.1±3.7 bpm; p=0.0013). The responses mediated by β2-adrenergic receptor stimulation, namely, a decrease in PEP and diastolic BP, were not potentiated. Although fenoterol prolonged the Q-Tc interval and decreased T-wave amplitude, these effects were not potentiated by theophylline. Oral theophylline potentiates the positively inotropic and chronotropic effects of fenoterol. We have investigated whether oral theophylline potentiated the cardiovascular effects of fenoterol administered by metered-dose inhaler. Eight healthy subjects were investigated on four occasions. On successive days (1 and 2), the subjects were given doses of 400μg, 600μg, and 800μg of fenoterol at 15-minute intervals (total dose, 1.8 mg) or matched placebo. Systolic time intervals, blood pressure, and the ECG were recorded at baseline and five minutes after each inhalation. Thereafter, the subjects were treated with slow-release theophylline for eight days. On days 9 and 10, the procedures on days 1 and 2 were repeated. The order of treatment was applied according to a crossover Latin-square design. The effects after theophylline alone were no different from placebo. Theophylline potentiated those hemodynamic effects of fenoterol due to enhanced cardiac sympathetic tone (mean±SE) as measured by a decrease in Q-S2I (–41.6±7.6 ms vs −27.3±5.9 ms; p=0.0004), an increase in systolic BP (23.5±2.8 mm Hg vs 9.0±5.3 mm Hg; p=0.00001), and an increase in heart rate (15.8±1.6 bpm vs 9.1±3.7 bpm; p=0.0013). The responses mediated by β2-adrenergic receptor stimulation, namely, a decrease in PEP and diastolic BP, were not potentiated. Although fenoterol prolonged the Q-Tc interval and decreased T-wave amplitude, these effects were not potentiated by theophylline. Oral theophylline potentiates the positively inotropic and chronotropic effects of fenoterol.