Minette compared 6-mg and 12-mg tablets of fenoterol hydrobromide with 20-mg tablets of meta-proterenol for their bronchodilator efficacy, as measured by changes in FEV1. Metaproterenol had a more rapid onset of action, but after one hour, both doses of fenoterol resulted in greater bronchodila-tion. Insignificant side effects were reported following the administration of fenoterol. Benjamin compared the effects of both 5-mg and 10-mg tablets of fenoterol with 40 mg of metaproterenol on the peak expiratory flow in asthmatic patients. Increases in this measurement were greater and more prolonged for the fenoterol-treated patients. In the same study, it was also shown that both of these doses of fenoterol resulted in greater and more prolonged bronchodilation than that produced by oral administration of 4 mg of albuterol (salbutamol). In a study of ten coal miners selected for the presence of reversible bronchial obstruction, Minette compared 12mg tablets of fenoterol with 2-mg tablets of albuterol and with placebo tablets. The ventilatory effects, as measured by mean changes in FEVi, were similar for the two sympathomimetic preparations.
Only two of the 20 patients in our study developed nervousness after receiving the 5-mg dose of fenoterol hydrobromide, while three patients experienced this complaint after receiving the 7.5-mg dose, as well as after the 10-mg dose. Only two patients developed shakiness on the two higher doses. This problem of nervousness and shakiness is common to all selective -adrenergic bronchodilator drugs given in standard therapeutic dosages.
The responses to administration of ephedrine in this study are interesting because they cast further doubt on the value of this agent as a bronchodilator drug. Tashkin et al showed that 25 mg of ephedrine produced significant bronchodilation between one and four hours after oral administration, whereas Chervinsky and Chervinsky found a “striking lack of efficacy” resulting from administration of 24 mg of ephedrine. These latter workers thought that their patients may have developed tachyphylaxis as a result of previous administration of the agent. Our patients had not received ephedrine in the weeks preceding the study, so the poor response to this drug could not be interpreted as being due to tachyphylaxis. Other investigators have also reported the relative lack of efficacy of ephedrine.
There are two previous studies of fenoterol in the American literature, which compared the effects of aerosol and oral administration of this drug with metaproterenol (orciprenaline); fenoterol was found to have a greater and more prolonged bronchodilator effect. In an extensive review of -sympathomimetic drugs used in the treatment of asthma, Leifer and Wittig claimed that the available literature makes fenoterol “appear to be the bronchodilator of choice in the world.” Although the present study does not provide grounds for such an enthusiastic claim, it is clear that fenoterol must be considered to be a bronchodilator drug of major importance.
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The results of this study demonstrate that when given orally in doses of at least 5 mg, fenoterol hydrobromide is an effective bronchodilator drug. This 5-mg dose resulted in improvements in FEVi and Gaw/Vb which appeared within two hours and lasted for six and three hours, respectively, after administration. On the other hand, at one hour after administration, the 7.5-mg and 10-mg doses produced improvements, which lasted up to eight hours for each measurement. No significant cardiac side effects were noted with these higher doses of fenoterol, indicating that this drug is a relatively selective stimulator of /fe-adrenergic receptors. Nervousness and shakiness did occur in a small number of patients in this study (Table 3). No other significant subjective or objective adverse effects were detected following any of the three dosages of fenoterol. Since the onset of action of fenoterol is delayed, with peak effects occurring from two to three hours after administration, its role in the treatment of asthma and other bronchospastic diseases will largely be in the prevention of exacerbations and in long-term maintenance therapy, rather than in the treatment of acute episodes.
We conclude from this study that fenoterol is a valuable bronchodilator drug, effective for up to eight hours after administration when given orally. The optimal dose would appear to be 7.5 mg in adult patients, but further studies should be performed to determine optimal regimens of dosage.
Earlier published articles describing this topic are given below: