Beta Adrenergic Agonists: Specific Beta Adrenergic Bronchodilators

Epinephrine is still the drug of choice for treatment of acute anaphylaxis where a combination of alpha and beta adrenergic properties are desirable. It is still employed in the treatment of severe asthma, and several recent studies have confirmed the efficacy of injections of 0.25 mg (0.01 mg/kg in small children) repeated at 15 to 20 minute intervals in the treatment of patients with acute bronchoconstriction. The principal alternative to epinephrine in the United States is terbutaline.

Even before the development of the newer adrenergic drugs, ephedrine was seldom employed alone. It has demonstrable but relatively weak bronchodilat-ing properties, its use is frequently associated with side effects, and as a single agent it probably has little place in the modem bronchodilator armamentarium.

The combination of ephedrine and aminophylline enjoyed many years of popularity, and it has been repeatedly demonstrated that the combination produces greater bronchodilation than either component alone. Furthermore, the two components complement each other since initially ephedrine contributes more to the bronchodilator effect, then, as subsensitivity develops to ephedrine, theophylline blood levels rise and the aminophylline becomes the principal contributor to the overall bronchodilator action. In both acute and chronic comparisons, the combination tablets have been roughly equivalent to the oral selective betas agonists and it has been suggested that there remains a role for this fixed combination medication in the treatment of patients who require only a mild bronchodilator.

Isoproterenol is a potent but nonselective and short-acting bronchodilator. Cardiac stimulation is usually not a problem with one or two metered doses, but becomes evident if the dose is increased. Isoproterenol is clearly unsuited for maintenance bronchodilator therapy or prophylactic use prior to exercise because of its brief duration of peak effect. The rapid onset of bronchodilator action does provide prompt relief of symptoms in most patients. However, in view of the proven superiority of the newer beta adrenergic agonists, there would appear to be little justification, other than habit, for the continued use of isoproterenol. Read article: “Modern Inhalers for Asthma“.

Bronchodilator Therapy

Isoetharine was the first widely employed drug which clearly had increased affinity for the betas adrenoceptors. Although it has slightly longer duration of action due to resistance to MAO, its pattern of bronchodilation closely resembles that of isoproterenol, and its use would also appear limited to rapid relief of acute attacks of bronchoconstriction. When repeated dosing is required, its decreased cardiac stimulation is an advantage.

By virtue of a shift of the hydroxyl groups to the third and fifth carbons on the benzene ring, metaproterenol is not susceptible to inactivation by COMT and can, therefore, be administered orally. The bulk of the side chain is unchanged from that of isoproterenol and, as might be expected, metaproterenol does not differ significantly from isoproterenol in its relative cardiac and bronchial potency. Furthermore, since metaproterenol is still susceptible to MAO, its duration of action is somewhat shorter than the selective betas adrenergic agonists whether administered orally or by inhalation. Because of this shorter duration of action, metaproterenol is not as well suited for either maintenance bronchodilator therapy or for prevention of exercise-induced bronchoconstriction unless the activity will be completed within two hours.

Terbutaline, albuterol, fenoterol and carbuterol are selective betas adrenergic bronchodilators and to date there is little evidence that any one is more selective for betas receptors than the others. All these drugs are effective orally and by inhalation. All are long-acting by any route of administration. All are largely free of direct cardiac stimulation in doses employed clinically; however, all share the same dose-limiting side effects—tremor and tachycardia. Both of these side effects are directly related to betas receptor stimulation. Stimulation of betas receptors in skeletal muscle causes tremor and betas stimulation of the smooth muscle in blood vessels supplying skeletal muscles results in decreased peripheral resistance, leading to reflex tachycardia and increased cardiac output.