Anticholinergic Drugs Print E-mail



The vagus nerve is the parasympathetic nervous system's pathway to the lungs. It affects airway muscle tone and mucus secretion. When the vagus nerve is stimulated, it releases acetylcholine, the cholinergic mediator. This mediator contracts the airway muscle and increases mucus production. Because this whole mechanism involves nerves, its effects are termed neurally mediated.

These cholinergic mediator effects can be stopped by a drug that blocks the action of acetylcholine. Atropine does just that. In fact, atropine inhalation was a standard asthma treatment until the 1930s, when the first crop of beta-stimulators (the general adrenaline imitators) rendered the side effects of atropine unacceptable. But though atropine was pushed off center stage, it never quite disappeared.

There is now new interest in anticholinergic bronchodilators spurred by two developments over the past 35 years. One is better understanding of the ways in which acetylcholine influences the diameter of healthy and diseased airways. Second has been development of effective atropine-like drugs thatunlike their parentare not absorbed into the general circulation. Local administration (by inhalation) of these atropine-derived drugs means much smaller doses are needed, and therefore side effects are much gentler.

The most extensively studied atropine derivative, ipratropium bromide, has been available since the early 1980s as an MDI under the brand name Atrovent. COPD patients were among the first test subjects for this drug. Its action and side effects were compared to the two commonly used bronchodilators. Most studies found COPD patients more responsive to ipratropium bromide than to beta-adrenergic and theophylline bronchodilators, either alone or in combination.

The time span is different, though. One dose of a beta-stimulator takes less than 30 minutes to achieve the maximum amount of bronchodilation, but it lasts for only 3 to 4 hours. One dose of the anticholinergic drug takes from 30 minutes to 3 hours to achieve maximum bronchodilation, but the effects last for 4 to 8 hours.

A growing number of doctors now prescribe these two different bronchodilators together to provide the best of both worlds. Combining the beta-stimulator's rapid onset with the anticholinergic's long-lasting activity is more effective than using either one alone (and permits beta-stimulator dosage to be lowered). (Theophylline and steroids also increase the potency of anticholinergic drugs.)

At present, though, there is little evidence to tell us whether ipratropium bromide and the beta-stimulator should be taken one right after the other or separated by a brief interval, or in which order they should be used. Most doctors we spoke with in the metropolitan New York area have their patients inhale Atrovent 15 to 30 minutes before using their prescribed beta-adrenergic bronchodilator. European pharmaceutical companies' solution is the production of "combination inhalers," now available in the United States.

For COPD patients with an obvious asthma component, anticholinergic therapy is most effective with bronchospasm triggered by inhaled irritants (such as cold air and cigarette smoke), and in patients whose symptoms become worse during stress. It is also particularly effective for COPD patients whose major symptom is coughing. Ipratropium bromide works well with any age patient but is at its best with adults over 40.

The initial introduction of ipratropium bromide met with concern that it would produce side effects similar to those of atropine. Atropine's undesirable consequences appear at doses equal to, or just slightly above, those needed to produce bronchodilation. Of particular concern for COPD patients are the severe inhibition of airway mucus secretion and mucociliary transport. Also, atropine is contraindicatedwarned againstin two conditions common in elderly patients: narrow-angle glaucoma and obstruction of the bladder's neck.

But this early concern was unfounded. Because so little inhaled ipratropium bromide crosses into the blood, side effects are almost nonexistent. Studies in asthmatic and chronic bronchitis patients taught us that ipratropium bromide does not substantially affect mucus production or consistency even with larger than normal doses. And inhaling four times the recommended dose does not increase intraocular pressure (a major worry with glaucoma's already dangerously increased pressure within the eye) or weaken the bladder muscle that maintains urinary continence.

In summary: ipratropium bromide is a safe, well-tolerated bronchodilator. Although with asthma it is less potent than beta-stimulators, in chronic bronchitis and emphysema it is usually equal or greater in potency.


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