BRORICHODILATORS



Drugs directed toward reducing airway tone can be divided into four groups . The sympathomimetics are the most potent broncho-dilators. Subcutaneous epinephrine and nebu­lized isoproterenol have a relatively short dura­tion of action and act on both beta-1 and beta-2 receptors, whereas epinephrine has additional,undesirable alpha effects. The development of noncatecholamine, beta-2-specific agents has im­proved the specificity of the sympathomimetic agents for the adrenergic receptor found in airway smooth muscle, but more importantly has in­creased the duration of action from 60 to 90 min­utes to more than 4 hours and permits oral ad­ministration. Aerosol therapy is the preferred route of administration, because the lower total dose reduces side effects. Oral use often leads to muscle twitching, and parenteral administration appears to markedly reduce their apparent beta-2 specificity.
When sympathomimetic agents are insufficient, the addition of a methylxanthine, such as theo­phylline, is quite useful. Effectiveness appears to be dose related, but the incidence of cardiac, gas­trointestinal, and neurologic toxicity is unac­ceptable at serum levels above 20 )xg/ml. It is most effective when a stable blood level is maintained. Factors that alter theophylline levels are shown in .

Anticholinergic agents were the first clinically available bronchodilators, but their usage de­clined because of concerns about their side ef­fects, specifically the purported inhibition of” lower airway secretions, which is no longer con­sidered to be a problem. As the importance of va-gally mediated mechanisms of bronchospasm have been elucidated, these agents have received renewed interest. They are particularly effective in patients with chronic airway obstruction, and newer agents with fewer extrapulmonary effects are being developed.

Corticosteroids are invaluable, although they do not work acutely to relieve airway obstruction. Their usage early and in sufficient doses in the treatment of acute asthma or the acute exacerba­tion of chronic airflow obstruction has been shown to lessen the degree of airway obstruction (over 12 to 24 hours), to decrease the total time of hospitalization, and to reduce recurrence. The complications of chronic administration limit their usefulness, although the introduction of po­tent, inhaled agents (beclomethasone) has signif­icantly reduced this problem. Unfortunately, an alternate-day regimen, to minimize steroid com­plications, is usually ineffective in patients with bronchospastic lung disease.

Inhaled sodium cromolyn prevents broncho­spasm and is not helpful in the management of an acute asthmatic attack. While stabilization of the mast cell membrane and the prevention of me­diator release are the major proposed mechanisms of action, it is also effective in forms of asthma without an atopic association. In asthmatics who are difficult to control, it is a useful drug to try before turning to chronic oral steroid therapy. The drug has a slow onset of action and should be used for three to four weeks before deciding on its ef­ficacy. It may also be used intranasally to relieve the symptoms of allergic rhinitis.
A suggested scheme for the administration of the bronchodilators is shown in Figure .