Antiasthmatic Agents
Authors: Bernstein Peter R. 
Published: July 2004

Asthma is an extremely complex condition characterized by variable and reversible airways obstruction combined with nonspecific bronchial hypersensitivity. Asthma affects 3–5% of the population and is one of the most common chronic illnesses. Clinically, there are several ways of classifying asthma, and treatment varies depending upon the classification. In extrinsic asthma, also called allergic asthma, experienced by adults and, most commonly, by children, it is possible to demonstrate specific causal agents, usually antigens, eg, animal danders, foods, drugs, house dust, pollens, or mold spores. Intrinsic asthma, also called idiopathic asthma, usually develops in adulthood; allergic factors are not demonstrable in intrinsic asthma. Episodes may be triggered by a variety of stimuli, eg, emotional state, exposure to cold air, or inert dusts. Both intrinsic and extrinsic asthmatics can be prone to exercise‐induced attacks. Individuals who experience a combination of extrinsic and intrinsic asthmatic reactions have mixed asthma. Current asthma treatments are not curative and historically have relied on pharmacologic intervention with bronchodilators. More recently the focal points of both treatment and research efforts have shifted from bronchodilators to agents which reduce the underlying inflammatory state. Management of extrinsic asthma usually includes manipulation of the patient's environment to minimize or completely eliminate the causal agent. Improvements in asthma treatment include the development of more effective, safer formulations of known drugs. Also, the use of reliable sustained release formulations has revolutionized the use of oral xanthines which have a very narrow therapeutic index. For many individuals, asthma symptoms tend to worsen at night and the inhaled bronchodilators do not usually last through an entire night's sleep. β2‐Agonists are widely used in the symptomatic treatment of asthma. Although both oral and aerosol formulations of these bronchodilators have been available for many years, advances have occurred in delivery technology with the development of dry powder aerosols. Nonselective β‐agonists can produce many undesirable side effects. Some selectivity in action was needed. Isoproterenol is a selective agonist at the β receptor. Aerosol administration of isoproterenol produces a prompt (2–5 min) intense bronchodilatation of relatively short (1‐h) duration, and has been widely used for many years. A significant advance in β‐agonist therapy occurred with the discovery of metaproterenol, C11H17NO3, which has a longer (4‐h) duration of action. Terbutaline, C12H19NO3, is an orally active agent having a duration of action of from 6–7 h. Terbutaline has about six times the selectivity of isoproterenol and is claimed to produce fewer side effects. Albuterol, C13H21NO3, also called salbutamol, is the most widely prescribed β2‐agonist for either aerosol or oral administration both in the United States and worldwide. There are several longer acting agents currently under clinical evaluation, eg, bitolterol, C28H31NO5; clenbuterol, C12H18Cl2N2O; and salmeterol, C25H37NO4. For many years oral xanthines were the preferred first‐line treatment for asthma in the United States. Within this class of compounds theophylene, ie, 1,3‐dimethylxanthine, is one member of a class of naturally occurring alkaloids. Common side effects of theophylline therapy for asthma include headache, dyspepsia, and nausea. More serious side effects can occur if blood levels are too high. Many derivatives of theophylline have been prepared. However, the most universal solution has resulted from the development of reliable sustained‐release formulations. The effectiveness of theophylline in the treatment of asthma seems to result from a combination of biological properties not clearly understood. Its predominant mode of action appears to be bronchodilation. Although the benefit of theophylline treatment is without question, its use is decreasing. Steroids use for the preventative treatment of asthma appears to be increasing, because of the identification of asthma as an inflammatory disease. It is known that steroids bind to cytosolic receptors. The steroid–receptor complex then enters the cell nucleus where the complex acts at specific sites and affects protein synthesis. The effect is to reduce the inflammatory response. While disodium chromoglycate (DSCG), C23H14Na2O11, enjoys modest success as a preventative antiasthmatic agent, it has never achieved the same level of popularity in the United States as in other markets, eg, the United Kingdom. Although it is considered one of the safest available antiasthmatic agents, it seems to work best as an adjunct to other therapy. The beneficial effect of atropine, used for centuries, is in preventing exercise‐induced asthma; it and other anticholinergic agents have no effect on bronchial hyperresponsiveness, the release of other mediators, or on the inflammatory process. Ipratropium bromide, C20H30BrNO3, a newer anticholinergic agent, seems to be useful in patient populations that show limited response to β2‐adrenergic agonists.