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Pharmacologic Management of Asthma
Guidelines Asthma Medications- Long-Term Therapy
- Immediate Relief
- Adjuvant Therapy
NAEP Guidelines for Pharamacologic Treatment of Asthma
| Classification | Severity of Symptoms | Nightime Symptoms | FEV | Treatment Options |
|---|---|---|---|---|
| Mild Intermittent | Sx < 2x/wk, otherwise asymptomatic | Sx <= 2x/mo | > 80% |
|
| Mild Persistent | Sx > 2x/wk, < 1x/day | Sx >= 2x/mo | > 80%, variabilty from 20 to 30% |
|
| Moderate Persistent | Daily Sx, daily use of a beta2 agonist | Sx >= 1x/wk | 60% to 80% |
|
| Severe Persistent | Continual Sx, limited physical activity | Frequent | < 60% |
|
Inhaled Corticosteroids
Inhaled corticosteroids are the most effective anti-inflammatory treatment available for persistent asthma. These drugs function by suppressing the generation of cytokines, recruitment of eosinophils, and release of inflammatory mediators. The clinical effects of these drugs include reduction in symptom severity, improvement in peak expiratory flows, diminished airway hyperesponsiveness, and possible prevention of airway wall remodeling. The dosage of corticosteroid needed varies depending on the specific product, delivery device and severity of the patient's asthma.Side Effects: Side effects include cough, dysphonia, and oral thrush. All of these side effects can be greatly reduced by use of a spacer and mouth washing after treatments. It is possible that inhaled corticosteroids may have a dose-dependant adverse effect on linear growth in some children. However, this effect is unpredictable and many studies have not found this result. Until this issues is further clarified the NAEP recommends that linear growth be closesly monitored and steroids dose decreased when possible.
Nedocromil/Cromolyn
Both cromolyn sodium and nedocromil have anti-inflammatory effects by blockading chloride cghannels and the modulation of mast cell mediator release and eosinophil recruitment. Both these drugs can be used in excercise-induced bronchospasm and in mild persistent asthma. Nedocromil appears to be more potent than cromolyn in inhibitng excercise-induced bronchospasm. Cromolyn and Nedocromil are generally comparable in patients with mild allergic asthma. Nedocromil may be more effective in patients with non-allergic asthma taking inhaled corticosteroids and may help to reduce the requirement for inhaled corticosteroids.Side Effects: Both drugs have a strong safety profile and can be used in children.
Leukotriene Modifiers
The two leukotriene modifying drugs available currently are Zafirlukast
and Zileuton. Zileuton is a 5-lipoxygenase inhibitor. Zafirluklast is
a leukotriene receptor antagonist. Leukotrienes are biochemical mediators released
from mast cells, eosinophils and basophils that contract airway smooth muscle,
increase vascular permeability, increase mucus secretions, and attract
and activate inflammatory cells in the airways. Although their role in treating asthma has
not been firmly established, current studies show that
these medications may be useful as an alternative to low dose inhaled
corticosteroids in treatment of mild persistent asthma. Both drugs are taken orally and are
currently approved for use in poeple 12 years and older.
Side Effects: Zafirlukast has been shown to cause a significant increase in the half-life of warfarin. Zileuto is an inhibitor of microsomal liver enzyme CYP3A4 and can inhibit the metabolism of theophyline, warfarin, and terfenadine. Zileuton has also been shown to have lover toxicity in some subjects and hepatic enzymes should be monitored
Oral Corticosteroids
Short-courses (3 to 7 days) of systemic steroids can be useful in speeding resolution of asthma exacerbations. They can also be useful in gaining prompt control of airway inflammation when starting treatment of persistent asthma. Long-term systemic steroids are reccomended for patients with severe persistent asthma. Like inhaled corticosteroids, these drugs function by suppressing the generation of cytokines, recruitment of eosinophils, and release of inflammatory mediators.Side Effects: The side effects of long-term steroid use include pituitary hypothalamic axis suppression, osteoporosis, growth suppression, dermal thinning, hypertension, diabetes, cataracts, muscle weakness, and Cushing's syndrome.
Short-Acting Beta2 Agonists
Short-acting beta2 agonists are the medications of choice in treating asthma exacerbations and excercise-induced bronchospasm. The regularly scheduled, daily use of these drugs is not recommended. The frequency of use of a beta2 agonist can be used to assess the effectiveness of asthma treatment.Side Effects: Tachycardia, skeletal muscle tremor, hypokalemia, increased lactic acid, and headache. Beta-2 selective agents are preferred due to decreased potential for excessive cardiac stimulation.
Long-Acting Beta2 Agonists
The principal action of long-Acting beta2 agonist is the relaxation of bronchial smooth muscle via the stimulation of beta2 receptors. These medications have a duration of action of at least 12 hours. Long-acting beta2 agonists are principally to be used as adjuvant therapy to anti-inflammatory treatment. They can used for long-term symptom control and are particularly useful in treating nocturnal asthma symptoms. These medications are also useful in excercise-induced bronchospasm. Unlike short-acting beta2 agonists, they are not to be used to treat acute exacerbations. Long-Acting beta2 agonists are available in both oral and inhaled forms, although the inhaled form is preffered due to fewer side effects.Side Effects: Tachycardia, skeletal muscle tremor, hypokalemia, prolongation of QTc interval in overdose.
Methylxanthines
Theophyline, the most common methylxanthine, causes mild to moderate bronchodilation. Some recent evidence suggests that theophyline may also have a mild anti-inflammatory component. Sustained release Theophyline's principle use is as adjuvant therapy and it is particularly useful in controlling nocturnal symptoms. Although not a preferred option, sustained-release theophyline can be used as a primary treatment in some patients with mild persistent asthma if cost and sompliance are considerations.Side Effects: Theophyline has a narrow therapeutic index and variable metabolism so serum theophyline levels should be closely monitored. Absorbtion and metabolism can be influenced by numerous factors including diet, hypoxia, systemic viral illness, hypoxia, age, phenobarbital, phenytoin, carbamazepine, macrolides, quinolones, rifampin, ticlopidine, and smoking. Adverse effects at normal doses include insomnia, gastric upset, aggravation of gastric ulcer or reflux, difficulty in urination in elderly males with prostatism. Acute toxicities include tachycardia, nausea, vomiting, tachyarrythmias, CNS stimulation, headache, seizures, hematemesis, hyperglycemia, and hypokalemia.