A Comparison of the Actions of Different Bronchodilators in Asthma

Abstract

The actions of the following pressurized bronchodilators were compared by administration to 24 asthmatics: (1) Medihaler Iso Forte, (2) Alupent, (3) Medihaler-duo, (4) Bronchilator, and (5) Prenomiser Plus. These contained one or more of the following: isoprenaline, orciprenaline, isoetharine, phenylephrine, atropine methonitrate, and thenyldiamine. The dose was a single discharge from the container. The response was assessed by calculating the mean percentage change in F.E.V. at intervals after inhalation. The mean peak rises were respectively (1) 49 4%, (2) 43 6%, (3) 36-2%, (4) 33 5%, and (5) 23'5 %. The amplitude of peak response to isoprenaline was related to the logarithm of the dose. Weight for weight, orciprenaline had a peak bronchodilator activity 41-5% that of isoprenaline and isoetharine 50%. The preparations did not differ significantly in the time taken to reach maximum response, which varied from 5 to 60 minutes; three-quarters of the maxima occurred within 15 minutes. The half-life for Alupent was 2 hours; for Medihaler-duo, which contains 240 /Ag. of-phenylephrine per dose, it was 1* hours; for the remaining preparations it was about 1 hour. The decay rate, after the first half-hour, was 6% of the basal F.E.V. per hour for Medihaler-duo; for the other preparations it was 10-12%. In the doses given, Alupent yielded 20% and 30% increases lasting 130 and 67 minutes; after Medihaler Iso Forte these lasted 78 and 46 minutes. Similar comparative experiments, designed to eliminate effects of dosage difference, are desirable. Rebound bronchoconstriction occurred in 23% of 92 experiments. There was no response to propellent alone. The mean percentage change in F.E.V. may not be the best way of expressing results. No fewer than 28 varieties of bronchodilator aerosol are available commercially in Britain today. Eight of these are supplied in solution, and 20 in pressurized containers. Almost all of them differ in composition and dosage. The confusion of choice presented by this wide range is scarcely resolved by the published results of numerous drug trials in which two or more bronchodilators have been compared.

`Metered' aerosols of bronchodilator drugs in clinical trials: Influence of the method of administration

“…In again confirming the greater utility of the [R,, x Vtg] calculation (compared with simple recording of R.) in estimating bronchial obstruction, our observations suggest that maximally effective inhalant doses may not be provided by conventional pressurized nebulizers whether given by well-instructed patients (Freedman, Meisner, and Hill, 1968) or by a physician (Ishikawa and Cherniack, 1969). Improvement in airways indices following selfdosage of the isoproterenol with phenylephrine aerosol was of lesser degree than the changes seen when the same mist was given by the physician from the identical apparatus, with the effects of both statistically inferior to those following the use of the breath-actuated device which did not require manual synchronization of mist release with patient inspiration.…”

A New Bronchodilator Response Grading Strategy Identifies Distinct Patient Populations

“…identified 80% with at least minimal and 50% with moderate or greater FEV1 BDR, while the ATS/ERS method identified only 20.6% positive.Interpretation of BDR for obstructive airways disease (OAD) patients in pulmonary laboratories has long been disputed. Nearly fifty years ago, Freedman et al suggested that most physicians would agree that a FEV1 increase <10% is valueless and that a 20%-30% increase was likely useful23 . In 1974, a CHEST advisory committee recommended positive BDR required FEV1 change in both percent and absolute volume24 .…”

Comparison of cumulative and non-cumulative techniques to measure dose-response curves for beta agonists in patients with asthma.

“…Doses of isoprenaline were given at five minute intervals since the response to inhaled isoprenaline is near maximum at this time and a longer time would have rendered earlier doses inactive by the end of the study. 3 The response was greater with the cumulative technique than the non-cumulative technique for FEVy, FVC, and PEFR, though the differences were significant only for FEVy. Since the magnitude of the difference between the two techniques was similar for FEVI, FVC, and PEFR-15%, 9%, and 16% respectively-differences in statistical significance presumably reflect the relatively small differences between the two techniques and the better reproducibility of FEV1 measurements.…”