Asthma Medicines

The use of epinephrine by injection for the treatment of asthma dates to as early as 1903. An aerosol form was developed around 1910. For many decades epinephrine was the only available medication for the treatment of bronchial asthma. Its use in the emergency setting has certainly saved countless numbers of lives.

In view of the fact that epinephrine is a nonselective agent that has potent effects on the heart and circulation, its use for treating bronchial asthma has declined. In elderly patients in particular, administration of epinephrine may result in increases in blood pressure and heart rate. These effects may contribute to the development of stroke and heart attack. For these reasons, emergency room treatment of bronchial asthma usually consists of the administration of a selective B-adrenergic agonist by nebulization.

For Anaphylaxis

Epinephrine is still an important medication for treating severe allergic reactions. It is the treatment of choice for a severe reaction known as anaphylaxis, a total body allergic reaction that may lead to collapse or shock. One example is the severe reaction to a bee sting in a sensitive individual. Injectable preparations of epinephrine that automatically inject a premeasured dose are available by prescription for highly allergic patients.

Over-the-Counter Medication

Over-the-counter nonprescription preparations of aerosol epinephrine should be avoided. These preparations are extremely weak and short acting with effects that may last only a few minutes, and therefore are commonly abused. With the far more effective treatment available for bronchial asthma I feel these agents would best be withdrawn since they may actually deter patients from seeking appropriate and necessary medical attention.

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The B-agonists were developed in the 1940s, with isoproterenol the first of the class. Like epinephrine (adrenaline) this agent has both beta-1 and beta-2 effects. Isoetharine was one of the first”selective”B2-adrenergic agonists introduced in the United States and it was followed by metaproterenol. With the development of selective B2-adrenergic agonists there is no place for the use of nonselective agents that have significant stimulatory effects on the heart and circulation. Further research has produced more potent and longer-acting selective agents.

For the Acute Asthmatic Attack: Short-Acting Agent

Several selective B2-adrenergic agonists are available for use. These agents are available as aerosol sprays delivered by metered-dose inhalers (MDIs), aerosol solution to be delivered by nebulization, dry powders for inhalation (DPI), short and long-acting tablets, and as syrups flavored for children. In the acute asthmatic attack the treatment of choice for prompt relief of symptoms is the administration of a short-acting B2-adrenergic agonist. B2-adrenergic agonists (albuterol, metaproterenol, pirbuterol, terbutaline, fenoterol, and bitolterol) have a rapid onset of action (within minutes) with a duration of action of four to six hours. The recommended dosage is two puffs every six hours as needed. These medications differ in potency as well as how fast they begin to work and when their peak effect is reached. There are also differences in how long the effect of the drug lasts. Fenoterol has never been made available in the United States. Its extremely rapid onset of action may have contributed to its overuse and it has been implicated in cases of fatal asthma in New Zealand. Table 1 lists the B2-agonists by generic and brand name as well as the types of preparations that are available.

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Cromolyn sodium, a derivative of khellin, an Egyptian herbal remedy, is a useful anti-inflammatory agent that may be used as an alternative to inhaled corticosteroids. In severe patients, cromolyn sodium (Intal) may be used in conjunction with steroids. Like the inhaled corticosteroids, cromolyn is also underused. This underutilization does not result from fear of adverse effects but rather from a misunderstanding of its application. Since its introduction, cromolyn has been the drug of choice for childhood asthmatics. From this early application it has been incorrectly assumed that it was a poor drug for adults, particularly those without allergic characteristics. Many studies, however, have documented that cromolyn may be an effective drug for asthmatics of all ages, even in patients with “intrinsic” asthma. It is also clear that cromolyn does not work for all patients. Like the inhaled corticosteroids, it is slow acting and therefore requires a trial of three to six weeks to assess response. Because of this, many patients abandon this drug before it has had an adequate trial.

How Does Cromolyn Work?

It is not clear how cromolyn sodium reduces inflammation. Some evidence has pointed to an action on inflammatory and allergy cells that prevents release of irritating chemicals that cause inflammation. There may also be an antagonistic action on nervous stimulation that prevents bronchoconstriction and reflex cough. Cromolyn has been demonstrated to prevent both the immediate and late reactions of asthma as well as exercise induced asthma in many patients.

How Cromolyn Is Supplied and Used

Cromolyn sodium was initially made available as a powder for inhalation. Unfortunately, this produced considerable coughing and wheezing. It is currently also available as an aerosol for metered-dose inhalers and in solution for nebulization. When used for nebulization it may be combined with a B2-adrenergic agonist. The recommended dosage is two puffs four times a day from an MDI or 20 mg in solution via a nebulizer, also four times a day.

Cromolyn is not an effective drug for acute asthmatic attacks and, like the inhaled corticosteroids, must be used as a preventive maintenance drug. For this reason cromolyn is best not started during an acute attack. It can be introduced toward the end of an oral steroid taper similar to the way that the inhaled corticosteroids are started. Also, like the inhaled corticosteroids, cromolyn can be used alone and does not necessarily require premedication with a B-adrenergic agonist.

Adverse Effects of Cromolyn

Besides being an effective drug, cromolyn has an extremely low incidence of side effects, which explains its first-line use in children where high-dose inhaled corticosteroids have been shown to slow bone development. In adults the inhaled corticosteroids are considered more effective, making cromolyn a second line agent. In those patients with adverse steroid effects cromolyn is an excellent alternative anti­inflammatory. There are few adverse effects to speak of. Occasionally, cough and wheezing may result from its inhalation. This can often be prevented with the use of a B-adrenergic agonist sprayed five to ten minutes before use or given in solution with cromolyn via nebulization. Rarely have total body effects been noted. An extremely small number of patients have noted joint pains and rash. These effects have resolved completely on discontinuation.

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