Inhaled short-acting beta-agonists (SABA), such as Albuterol and Levalbuterol, are the mainstay of treatment in intermittent asthma, and symptoms are completely resolved with their use. Onset of action for SABAs is relatively short as peak plasma concentrations of nebulized or orally inhaled albuterol often occurs in less than 15 minutes. They cause bronchodilation through β2 agonism.
Mild persistent asthma requires advancement to step 2 on the asthma management protocol. In addition to a rescue inhaler (short-acting beta-agonist), daily low-dose inhaled glucocorticoids, such as Budesonide or beclomethasone are commonly used to control inflammation in patients with persistent asthma.
Leukotrienes are chemical mediators of the allergic response, and are overactive in asthma. The leukotriene receptor antagonists, Montelukast and Zafirlukast, block leukotriene receptors, which decreases bronchoconstriction, hypersecretion and eosinophil recruitment.
Cromolyn prevents degranulation of mast cells, preventing the release of histamine and leukotrienes. This decreases bronchospasm but does not cause acute bronchodilation. Cromolyn is an alternative option for prophylaxis in patients with exercise-induced asthma, or patients with predictable asthma exposures.
Theophylline non-selectively inhibits phosphodiesterase, which increases levels of circulating cyclic adenosine monophosphate (cAMP) and stimulates release of catecholamines and epinephrine. This causes bronchodilation along with CNS and cardiac stimulation, among other effects. Due to only moderate benefit and a high side-effect profile, it is uncommonly used in the United States.
An alternate step 3 option is to add a long-acting beta-agonist to the low-dose inhaled corticosteroids, and short-acting beta-agonist of step 2. Long-acting beta-agonists are used daily, and is given in combination with inhaled glucocorticoids. Common combinations are Budesonide-Formoterol (Symbicort) and Fluticasone-Salmeterol (Advair).
Zileuton acts on the front end of the leukotriene pathway through inhibition of the 5-lipoxygenase enzyme, which is involved in the production of leukotrienes.
Moderate persistent asthma requires advancement to step 3 on the asthma management protocol. Step 3 includes increasing to medium-dose inhaled corticosteroids (Budesonide) daily for management of airway inflammation, in addition to as needed use of a short-acting beta-agonist.
Step 4 of the protocol calls for escalation to medium-to-high dose inhaled corticosteroids, in combination with a long-acting beta- agonist (LABA), and all other previous medications used (SABA, mast cell stabilizer, leukotriene inhibitors, and/or theophylline).
Omalizumab is an anti-IgE monoclonal antibody that can be used in patients with severe disease, who have “allergic asthma” or asthma that is driven by an IgE response. This can be determined with high blood IgE levels, or positive allergen skin testing. Omalizumab is given every 2 to 4 weeks via subcutaneous injection.
Some patients with severe asthma may require systemic steroids to control their airway inflammation. These offer the most potent and effective asthma controller medication, however, they have severe side effects when used for a long duration. The lowest effective dose of systemic steroids should be used in order to avoid Cushingoid side effects. They can be given in short bursts to control exacerbations, or in low daily doses for patients with frequent, severe exacerbations.
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