Considerations of Anticholinergic Drug, Ipratropium Bromide (Sch 1000), as an Aerosol in Chronic Bronchitis and Asthma

Atropine has been administered parenterally and by inhalation to prevent and curtail asthmatic attacks. Gold and associates showed that procedures decreasing vagal stimulation, including intravenous or aerosol treatment with atropine, could prevent increases in airway resistance caused by several different antigens in dogs. Pretreatment of asthmatic patients with atropine can block their shortterm response to methacholine and certain antigens. Intravenous administration of atropine to dogs prevented bronchospasm induced by intravenous or aerosol administration of serotonin (5-hydroxytryptamine).

Aerosol administration of ipratropium can reverse acetylcholine-induced bronchospasm in humans or, if used as a pretreatment, prevent allergen-induced obstruction. Nervous regulation of the airways is under sympathetic and parasympathetic control Animal models suggest a predominant role of the vagal constrictor pathways. In humans with chronic bronchitis, the bronchodilator effects of an anticholinergic drug may be equal to or greater than those exerted by a sympathomimetic agent.


Our data show that in patients with bronchial asthma, ipratropium bromide, particularly when given in doses of 40/ig and 80/ig, usually has as rapid an onset of action as isoproterenol and a longer duration of action. Other studies have confirmed the rapid onset of action of ipratropium.

It is apparent from our study and others that ipratropium is as efficacious a bronchodilator drug in asthma as are the -adrenergic agents and can probably be used without risk of cardiovascular side effects. Comparisons with -adrenergic agents suggest that ipratropium may have a more prolonged action than isoproterenol (more information about ipratropium).

Analyzing the data in any group of patients with chronic bronchitis is a more difficult but intriguing task. One of the major problems is that of definition. The American Thoracic Society’s definition, according to which sputum must be produced daily for three or more months during a period of more than two years, does not adequately define the population. Production of sputum, even in individuals with a history of smoking or occupational exposure, is not invariably a sign of chronic bronchitis.  Intrinsic and extrinsic asthma, as well as bronchiectasis, are associated with chronic production of sputum. Therefore, a population of chronic bronchitic patients who show reversible obstruction may represent a subgroup of this entity. Most chronic bronchitis is thought of as being manifested by irreversible airway obstruction, at least as demonstrable by tests of pulmonary function performed before and after the administration of broncho-dilator drugs. The bronchodilator drugs employed in the past have nearly always been of the ^-adrenergic or methylxanthine groups. We only admitted to our study patients with chronic bronchitis who demonstrated an increase in FEVi of at least 20 percent after inhaling isoproterenol. Consequently, no claim regarding the efficacy of isoproterenol or ipratropium in the general population of patients with chronic bronchitis can be made. What can be stated is that in individuals with chronic bronchitis or chronic asthmatic bronchitis in whom airway obstruction has been found to be reversible by administration of isoproterenol, 10/xg and 20/xg doses of ipratropium proved roughly comparable to isoproterenol in the onset and intensity of effect and were possibly slightly superior in the duration of action. At the higher doses, ipratropium was superior to isoproterenol with regard to the magnitude and duration of effect in this subgroup of patients with chronic bronchitis. Several other studies (none published in this country) have shown that airway obstruction in chronic bronchitic patients was reduced after treatment with ipra-tropium. See the article about the effect of passive smoking on lung function in asthmatics:

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Irreversible airway obstruction

Some concern has been voiced about the use of atropine-like agents because of possible cardiovascular, ocular, and secretion-drying effects. The results of our study reflect no significant alterations of pulse or blood pressure at any of the doses of ipratropium that we tested. Other studies have confirmed this paucity of cardiovascular side effects. Dryness of the mouth and scratching in the trachea have been reported as side effects at incidences ranging up to 25 percent. These side effects were not encountered in our study.

In conclusion, we have seen that aerosol administration of ipratropium in doses up to 80/xg is a more effective bronchodilator therapy than isoproterenol in patients with asthma, chronic bronchitis, or chronic asthmatic bronchitis associated with partly reversible airway obstruction. A major advantage over isoproterenol is the considerably prolonged duration of action, which is comparable for bronchitic, as well as asthmatic patients. Cardiovascular, ocular, and subjective side effects and the effects on sputum appear to be minimal. Long-term studies are still required to assess the efficacy and safety of continuous protracted treatment.

Other facts on this subject you can read in the following articles:

Bronchodilator Action of the Anticholinergic Drug, Ipratropium Bromide (Sch 1000), as an Aerosol in Chronic Bronchitis and Asthma
Data of Anticholinergic Drug, Ipratropium Bromide (Sch 1000), as an Aerosol in Chronic Bronchitis and Asthma