Asthma medications.

The National Asthma Education and Prevention Program--Expert Panel Report 3 (NAEPP EPR3) guidelines have been formulated essentially to assess asthma severity to initiate therapy, and to assess asthma control to monitor and adjust therapy. Various medications are used to control the severity of asthma, and they are administered to manage an assortment of pathophysiologic manifestations, including variable recurring symptoms, airflow limitation, airway hyperresponsiveness and inflammation.

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Asthma medications are classified into different categories based on the mechanisms of actions and side effects of the drugs. These categories include the following types of drugs: corticosteroids, beta-2 agonists, anticholinergic bronchodilators, methylxanthines, leukotriene modifiers, immunomodulators and mast cell stabilizers. The references to the NAEPP EPR3 guidelines in this article pertain to asthmatics 12 years of age and older.

Corticosteroids

Corticosteroids play a strategic role in the treatment and control of asthma. The anti-inflammatory effects of corticosteroids render them essential for treating chronic asthma, as well as asthma exacerbations. Airway inflammation has become known as the primary pathophysiologic expression of asthma, thereby accentuating the administration of corticosteroids in treating this disease.

Controlling airway inflammation is the cornerstone of treating and controlling asthma signs and symptoms. In fact, the definition of asthma recognizes the central role chronic airway inflammation plays in the presentation of clinical signs of asthma. Airway inflammation is known to be responsible for airway hyperresponsiveness and airway obstruction from which emerge the signs and symptoms of asthma.

For the management of asthma, corticosteroids are administered via either the systemic (orally or intravenous) or the inhaled route. Inhaled corticosteroids are given to treat mild, moderate and severe persistent asthma. Intermittent asthma is the only classification of asthma that is managed without a steroid. Mild, moderate, and severe persistent asthma, treated according to steps two through six, require a corticosteroid for asthma control.

Mild persistent asthma is treated with a low-dose inhaled corticosteroid (ICS), for example, fluticasone (Flovent 44). Moderate persistent asthma demands the use a medium-dose ICS such as Flovent 110. Flovent 220, a high-dose ICS, is used to help manage severe persistent asthma. Other ICS used for controlling asthma in steps two through six include beclamethasone, budesonide, flunisolide, mometasone, ciclesonide and triamcinolone. For treating severe persistent asthma in step six, the patient may receive both a high-dose ICS and an oral corticosteroid.

For the treatment of an asthma exacerbation in the emergency department, the NAEPP EPR3 guidelines recommend systemic steroids for patients who demonstrate moderate-to-severe attacks that are not responsive to the administration of a short-acting, beta adrenergic bronchodilator.

Beta-2 Agonists

Beta-2 agonists are the keystones of treatment for chronic and acute asthma. As a class, these medications are analogues of epinephrine, and they cause the relaxation of bronchial smooth muscle that comprise most of the airways throughout the tracheobronchial tree. The more recent generation of beta-2 agonists, including albuterol, levalbuterol, bitolterol and pirbuterol, have minimum untoward cardiovascular effects, making them ideal for managing all forms of asthma.

In terms of asthma management, beta-2 agonists are classified as either short-acting beta agonists (SABAs) or long-acting beta agonists (LABAs). LABAs such as salmeterol and formoterol, given in combination with the appropriate dose of ICS, are frontline medications for the day-to-day treatment of moderate and severe persistent asthma. Their bronchodilation effects last about 12 hours. Therefore, these patients use the combination drugs Advair or Symbicort twice daily. Advair is a dry powder inhaler containing 50 mcg of salmeterol available in combination with one of three different doses of fluticasone (100 mcg, 250 mcg and 500 mcg.)

Symbicort contains the LABA formoterol (4.5 mcg) available with two different doses of budesonide 160 mcg and 80 mcg. The LABA-ICS combinations may be used daily by asthmatics who have symptoms consistent with mild, moderate, and severe persistent asthma. LABAs are not beneficial for treating acute onset of asthma symptoms or for an asthma exacerbation. LABAs are never to be used as monotherapy in asthma, only in combination with an ICS.

SABAs, also described as rescue medications, are administered to provide quick relief of bronchoconstriction, cough, tightness of the chest and wheezing. All four categories of asthma, including acute onset of asthma symptoms, exercise-induced bronchospasm and asthma exacerbation indicate the use of SABAs because these drugs have an onset of three to five minutes, and last up to four hours. In fact, 2.5 mg to 5.0 mg can be nebulized every 20 minutes for three doses. If relief has not been achieved, 2.5 mg to 10 mg of albuterol can be administered every one to four hours. If no relief continues, the patient can receive 10 mg to 15 mg of albuterol per hour.

Anticholinergic Bronchodilators

Anticholinergics are a class of medications that inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. Anticholinergics are used to treat a variety of disorders such as gastrointestinal cramps, urinary bladder spasm, motion sickness and asthma.

Anticholinergic bronchodilators are considered quick-relief medications for asthma management in the emergency department. However, evidence is lacking for long-acting anticholinergics such as tiotropium bromide producing additional benefits to beta-2 agonists in long-term therapy. Nonetheless, ipratropium bromide is available in a metered dose inhaler and generically as a nebulized solution. Ipratropium bromide is also available in combination with albuterol.

Methylxanthines

Methylxanthines, which are phosphodiesterase inhibitors, promote bronchodilation. Theophylline, a methylxanthine, affords moderate bronchial smooth muscle relaxation. Consequently, theophylline is not considered a preferred medication for the treatment of mild persistent asthma. Instead, it is regarded as an alternative drug. Methylxanthines have no role in controlling acute symptoms or during an exacerbation of asthma.

Leukotriene Modifiers

Leukotrienes are derived from arachidonic acid and are preformed mediators located within mast cells. When the integrity of the mast cell membrane is compromised by antigen-antibody reactions on the cell's surface, leukotrienes and other mediators are released. Leukotrienes are inflammatory molecules responsible for bronchoconstriction. Leukotrienes appear to trigger acute asthma attacks and cause long-term hypersensitivity of the airways in asthma.

Leukotriene modifiers are categorized as either leukotriene receptor antagonists (LTRAs) or 5-lipoxygenase pathway inhibitors. Montelukast and zafirlukast are LTRAs that block the actions of leukotrienes, thereby preventing airway hypersensitivityincreased mucus secretion, and increased vascular permeability by alleviating airway inflammation. Zileuton, which is a 5-lipoxygenase inhibitor, appears to benefit person treated for exercise-induced bronchospasm and aspirin sensitivity. Leukotriene modifiers are used as alternate therapy for the long-term control of mild and moderate persistent allergic asthma.

Immunomodulators

Omalizumab is a monoclonal antibody that binds to immunoglobulin E (IgE), thereby neutralizing IgE-mediated responses, which occur from the degranulation of basophils and mast cells. Subcutaneously administered, omalizimab neutralizes IgE antibodies, and prevents antigen-antibody reactions from taking place on the surface of basophils and mast cells. The subsequent release of mediators is avoided.

Omalizumab has been deemed appropriate for patients who have allergic asthma, and for those who have severe persistent asthma that is difficult to control with the combination of high-dose ICS and LABA.

Mast Cell Stabilizers

Cromolyn sodium is an anti-inflammatory agent that helps stabilize the surface membranes of eosinophils and mast cells. Consequently, various mediators contained inside these cells are prevented from causing airway inflammation, vascular permeability, and bronchoconstriction. Cromolyn sodium is not a preferred medication, but is recommended as an alternative treatment for mild persistent asthma. Patients who have exercise-induced bronchospasm or allergic asthma may benefit from the prophylactic use of this class of drugs. However, beta-2 agonists are more effective for prophylaxis of exercise-induced bronchospasm.

The armamentarium of drugs available for the treatment of asthma is considerable. Respiratory therapists must be knowledgeable of the application of these medications as disseminated by the NAEPP EPR3. At the same time, respiratory therapists must educate patients with asthma about the use these medications.

by Bill Wojciechowski, MS, RRT

William Wojciechowski, MS, RRT, is chair and associate professor in the department of cardiorespiratory care at the University of South Alabama, Mobile.