The National Asthma Education and Prevention Program (NAEPP), Expert Panel Report 2 (EPR 2), associated with the National Heart, Lung and Blood Institute and the National Institutes of Health, published Guidelines for the Diagnosis and Management of Asthma in July 1997.1 In June 2002, a guideline update was introduced.2 The NAEPP EPR2 offers a stepwise approach to treating asthma patients, which is meant to assist and not to replace providers? clinical decision making in regard to the patient.1 This approach requires that patients must first be properly staged according to asthma symptom severity and then placed on particular medications and doses that have been proven effective for patients in their individual stage (Tables 1 and 2).
Pharmacologic therapy for asthma is divided into 2 categories: long-term-control and quick-relief medications. The long-term controllers are to be taken on a daily basis by patients with persistent asthma, to prevent asthma symptoms. The quick-relief medications, as the name suggests, offer fast alleviation of acute symptoms. Long-term-control medications include inhaled corticosteroids (ICSs), long-acting inhaled beta2-agonists (LABAs), leukotriene modifiers, mast cell stabilizers, and methylxanthines. Quick-relief medications include short-acting beta2-agonists and oral prednisone.
ICSs are used for their anti-inflammatory properties. These properties include blocking a late reaction to an allergen, reducing airway hyperresponsiveness, and inhibiting the migration and activation of inflammatory cells to the airways. 1 Because asthma is an inflammatory disease, ICSs are considered first-line treatment for all patients with persistent asthma. Available ICSs include fluticasone, budesonide, triamcinolone, beclomethasone, and flunisolide. These medications come in varying forms, including metered-dose inhalers (MDIs), dry-powder inhalers (DPIs), and a nebulizer solution.
Most side effects of ICSs are localized to the oral cavity because systemic effects are possible only at very high doses. All patients using ICSs should rinse their mouth after inhalation to prevent oral candidiasis and to decrease the risk for hoarseness. A pharmacist should review and reevaluate patients? proper inhaler technique on a regular basis (Table 3).
The NAEPP Expert Panel evaluated numerous trials to determine whether ICSs improve long-term outcomes in children. The evidence shows that ICSs improve asthma control in children with mild-to-moderate persistent asthma, when compared with as-needed beta2-agonists. They also are superior to other long-term-control medications, including cromolyn, nedocromil, theophylline, and leukotriene modifiers. 3 Researchers also had thought that ICSs could stunt children?s growth, and therefore these medications were not used as often in children. Several studies, including 1 evaluating the effects of budesonide use in children for >9 years,3 have shown that children using daily ICSs do in fact achieve normal adult height. Because of the proven safety and efficacy of ICSs, the NAEPP guidelines recommend more aggressive ICS dosing in children with asthma.
Airway hyperresponsiveness, another characteristic of asthma, includes bronchospasms and bronchoconstriction. The beta2-agonists stimulate the beta2 receptors in the airways, causing smooth muscle relaxation, airway opening, and decreased hyperresponsiveness. Salmeterol and formoterol are long-acting beta2-agonists (LABAs). They have a slower onset of action (15-30 min) and a longer duration (>12 hr) than albuterol.
LABAs are not meant for acute symptom relief and should be used no more than every 12 hours. Overuse of LABAs may result in tachycardia. LABAs should not be used alone in persistent asthma; ICSs are still considered first-line therapy.
The leukotriene modifiers include montelukast, zafirlukast, and zileuton. Leukotrienes are biochemical mediators released from mast cells, eosinophils, and basophils. They cause airway contraction, increase vascular permeability, increase mucous secretions, and attract inflammatory cells to the airways.1 These medications inhibit leukotriene receptors, thereby preventing the effects of leukotrienes.
Montelukast also has been FDA-approved for the treatment of allergic rhinitis. It may be used in adults and children 2 years old, and it is dosed the same for asthma and for allergic rhinitis. Zafirlukast and zileuton are FDA-approved for asthma only, both for adults and for children 5 years old and 12 years old, respectively.
Mast Cell Stabilizers
Cromolyn and nedocromil stabilize mast cells, thereby blocking the reaction to an allergen(s). These are very safe medications and were once firstline therapy for children. Therapeutic response usually takes up to 2 weeks; however, a 4- to 6-week trial is recommended to see optimal effects.
Methylxanthines benefit asthma patients by causing bronchodilation. There is a risk for toxicity associated with their use, and they are no longer commonly used. Signs of toxicity include tachycardia, nausea, vomiting, seizures, insomnia, nervousness, and arrhythmias.
Quick-relief medications include inhaled short-acting beta2-agonists (SABAs) and, for more severe asthma exacerbations, an oral burst of prednisone.
SABAs? quick onset of action gives users almost immediate relief. Patients should use these products as needed for asthma symptoms, and they should keep an inhaler with them at all times. Albuterol, pirbuterol, and levalbuterol are examples of SABAs. Levalbuterol, available as a nebulizer solution only, is the R-isomer of albuterol. Its proposed advantage over albuterol is that it causes fewer side effects.
Oral prednisone for asthma patients is used most often as short-course therapy (?burst?) for worsening asthma symptoms due to an acute episode. Its anti-inflammatory effects and oral dosing allow for rapid improvement during an asthma exacerbation.
A medication less commonly used in asthma patients is the anticholinergic drug ipratropium. It acts as a bronchodilator and decreases mucus gland secretion in the airways. It is not recommended by the NAEPP for the treatment of asthma exacerbations and is usually reserved for use in the emergency department in addition to albuterol.
Devices are available to allow asthma patients to administer medication more easily?such as nebulizers and spacers. Nebulizers turn liquid medication into a fine mist that is easily inhaled. Budesonide, albuterol, ipratropium, and levalbuterol are available in nebulizer solutions.
Spacers attach to MDIs and act as a holding chamber. They are good for patients who have a hard time coordinating inhalation with actuation, or for anyone using a steroid inhaler, to decrease drug deposition in the mouth.
Peak-flow meters are monitoring devices that allow patients to see how well their asthma is controlled. Changes in peak-flow readings can indicate an asthma attack before it occurs. This warning allows patients to adjust medication administration according to an action plan given by their doctor.
The Role of Pharmacists
Pharmacists indeed have a key role to play in the treatment of asthma patients. They must be aware of exposures that can trigger an attack and be able to teach patients how to avoid them. Common triggers include cigarette smoke, dust mites, cockroach excrement, fumes, weather changes, pet dander, respiratory infections, and exercise.
Pharmacists should recommend a yearly influenza inoculation for all asthma patients who do not have a contraindication to the immunization. Albuterol used shortly before exercise helps to prevent exercise-induced asthma symptoms.
In summary, it is a pharmacist?s duty to be educated on asthma medications and to be prepared to meet the needs of patients. They have a responsibility to teach patients ways to avoid asthma exacerbations, how to monitor their symptoms, how to use medications appropriately, and, oftentimes, to guide prescribers in appropriate drug choice.
For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. D. Ryan, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: firstname.lastname@example.org
One study linked multiple pregnancies to an increased risk of developing atrial fibrillation later in life, and another investigated the association between premature delivery and cardiovascular disease.
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