Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room
Anthony S. RebuckKenneth R. ChapmanRaja T. AbboudPeter D. ParéHarvey KreismanNorman WolkoveF Vickerson
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Ipratropium bromide
Fenoterol
Anticholinergic agents
Vital capacity
Ipratropium
Bronchodilatation
Ipratropium bromide
Fenoterol
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Ipratropium bromide
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Summary: The bronchodilator effects of 40 μg ipratropium bromide (I) and 400 μg fenoterol (F) by pressurised aerosol and both drugs in combination were compared with placebo (P) in a double‐blind study in eight patients with chronic, partially reversible airways obstruction. The four treatments were (1) IP, (2) PF, (3) IF and (4) PP, with the second aerosol administered two hours after the first. Both drugs produced significant bronchodilatation for five hours, the response being greater and more rapid in onset with fenoterol. Both drugs in combination (IF) produced significant additive bronchodilatation from three to six hours after fenoterol. This additive effect may have been due to the improved lung function caused by ipratropium bromide and does not imply a synergistic effect. There were no side‐effects reported. The results suggest that both ipratropium bromide and fenoterol are effective bronchodilating agents in patients with chronic asthma.
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Eighteen patients hospitalised with acute bronchial asthma are examined. Nine were given aerosol treatment with an ipratropium bromide solution and 45 minutes later with a phenoterol solution. The remaining 9 were given the same treatment in reverse order. The results obtained showed that phenoterol has a stronger bronchodilatory activity than ipratropium bromide, especially when administered after the anticholinergic product.
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Two double-blind, placebo-controlled studies were performed in patients with chronic, partially reversible airflow limitation to compare ipratropium bromide and fenoterol administered singly with the combination treatment. In the first study, ipratropium bromide, 40 µg, or placebo was administered 2 h before fenoterol, 400 µg, or placebo, both by metered-dose inhaler. The combined treatment demonstrated significant additive bronchodilatation with an improved forced expiratory volume in 1 s (FEV1) response from 3 to 6 h after fenoterol administration. In the second study, ipratropium bromide, 0.5 mg, fenoterol, 2.0 mg, or placebo was administered by aerosolized solution with a nebulizer. The FEV1 response to the combined treatment, administered at the same time, was significantly greater than for fenoterol (0.5, 0.75, 4 and 6 h) and for ipratropium bromide (0.25–1.5, and 4 h) at various times. There was a disproportionate increase in forced vital capacity (FVC) compared with FEV1 for all treatments, suggesting dilatation and increased stability of small airways. In both studies, no synergistic effect is implied. In summary, additive bronchodilatation may be achieved with combined ipratropium bromide and fenoterol treatment by metered-dose inhaler or aerosolized solution.
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A double-blind, randomized trial was carried out in 48 children to assess the effects of inhaled ipratropium bromide, fenoterol or a combination of both drugs in treating their moderately severe acute asthma. Doses were adjusted according to the age of the patients and administered by nebulizer. Measurements of pulse rate and respiratory rate and assessment of the severity of symptoms were made at fixed intervals during the first 2 hours on treatment. Repeat nebulizations were given, if necessary, at 2-hourly intervals. The results suggested that fenoterol provided the most adequate treatment and there was no evidence to indicate that the addition of ipratropium produced any improved benefit.
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We evaluated the effect of anticholinergic and beta-adrenergic inhaled bronchodilators, alone or in sequence, in 11 patients with chronic obstructive pulmonary disease. We compared the agents albuterol and ipratropium bromide when each was used as a single aerosol in the maximal dose. After giving a maximal dose of one agent, we compared the effect of adding the other with that of adding a placebo. When used alone, both bronchodilators significantly increased airflow and relieved hyperinflation, and there was no significant difference between the two. After the improvement with the initial bronchodilator, the subsequent effect of a second inhaled bronchodilator was not greater than that of placebo. These results suggest that in the treatment of chronic obstructive pulmonary disease, these two aerosols are usually equipotent in maximal doses and the addition of a second agent is of no practical value. The data support the prescription of a single inhaled agent in most cases but do not rule out the value of combinations of agents under special circumstances.
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Ipratropium bromide (0.5 mg) and fenoterol (2 mg) produced equivalent peak bronchodilatation between 1 and 2 h after administration to eight patients with chronic partially reversible airways obstruction. The duration of action compared with saline was 6 h for ipratropium and 4 h for fenoterol. Both drugs in combination produced greater bronchodilatation than either drug alone. The increase in FVC was disproportionately greater than FEV1 with both drugs and saline, suggesting relief of obstruction of small airways.
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The efficacy and safety of a novel fenoterol/ipratropium bromide metered-dose inhaler (MDI) formulated with a non-chlorinated propellant, HFA134a, has been compared with placebo and the conventional chlorofluorocarbon (CFC)-containing fenoterol/ipratropium bromide inhaler (Berodual) in asthmatic patients. Fifty-two patients were enrolled in two centres. The fenoterol/ ipratropium bromide treatment produced significantly (P < 0.0001) greater bronchodilatation than placebo. There were no significant differences between the mean peak and average forced expiratory volume in the first second (FEV1) for patients receiving 2 puffs of the fenoterol/ipratropium bromide HFA134a inhaler and the conventional CFC inhaler. In addition, time to onset and duration of efficacy were comparable for these two treatments. None of the patients showed a fall of > or = 15% in baseline FEV1 or needed rescue medication within 30 min after inhalation of the test drug. No paradoxical bronchoconstriction was observed as measured by sGaw. The two inhaler formulations were well tolerated. A taste-related complaint, lasting for a few minutes after inhalation, was reported by a higher proportion of patients who inhaled the HFA134a formulation, mainly by patients selected in one of the two centres. In conclusion, a dose of 100 micrograms fenoterol/40 micrograms ipratropium bromide inhaled from a MDI containing HFA134a propellant is safe and provides effective bronchodilatation of equivalent degree, onset and duration of action to the same dose from the conventional CFC formulation.
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