Asthma & COPD Treatments
Overview
Asthma and
COPD are obstructive respiratory diseases characterized by airflow obstruction, chronic inflammation, and airway remodeling.
Asthma is defined as intermittent, reversible obstruction and hyper-reactivity with excessive mucus production in the bronchi.
COPD is chronic, progressive, irreversible obstruction.
COPD is an umbrella term that includes chronic bronchitis, small airway disease, and emphysema.
Asthma-COPD overlap syndrome, which involves the airway hyper-reactivity associated with asthma plus elements of COPD.
Asthma and/or COPD have shared treatment goals:
Open their airways and reduce air trapping, which will relieve dyspnea, and, reduce airway remodeling and prevent exacerbations.
Bronchodilators are used to treat both asthma and COPD.
Beta-2-adrenoreceptor agonists
Beta-2-adrenoreceptor agonists (often shortened to simply "beta-2 agonists") bind beta 2 receptors on the bronchial smooth muscle, which increases local cAMP and induces smooth muscle relaxation and bronchodilation.
Beta-2 agonist bronchodilators may cause adverse effects associated with sympathetic activation (tremors, irregular heartbeat).
Short-acting beta-2 agonist bronchodilators (SABAs) are used as "rescue" interventions for acute dyspnea due to bronchoconstriction and hyper-reactivity; they are effective within 1-5 minutes of administration and the effects last up to 4 hours.
Examples of selective beta-2 agonists: albuterol, terbutaline, pirbuterol, and metaproterenol ("ols").
Non-selective beta agonists, such epinephrine, are associated with more adverse effects; fortunately, selective beta-2 agonists have replaced them.
Long-acting beta-2 agonist bronchodilators (LABAs) are administered once or twice daily as "maintenance" treatments to maintain open airways; onset is slower, but the effects last for 12-24 hours.
Examples of LABAs: salmeterol and formoterol ("ols").
Muscarinic antagonists
Muscarinic antagonists are also used to treat asthma and COPD. They block acetylcholine from binding muscarinic receptors in the bronchial smooth muscle, which prevents bronchoconstriction; these drugs also reduce vagal-mediated mucus secretion in the bronchi.
Muscarinic antagonist bronchodilators are associated with dry mouth, dizziness, gastrointestinal problems, and cough.
Short-acting muscarinic antagonist bronchodilators (SAMAs) are used as
"rescue" treatments; they take effect within minutes of administration and last about 4 hours.
Example: Ipratropium is a commonly used short-acting muscarinic antagonist.
Long-acting muscarinic antagonist bronchodilators (LAMAs) are used for maintenance therapy, as their effects last 12-24 hours.
Examples: Tiotropium, aclidinium, and umeclidinium are examples of these drugs ("iums").
Dual Therapy
Beta-2-adrenoreceptor agonists and muscarinic antagonists work synergistically to open the airways, so they are often used together in dual therapy to maximize their effects.
Methylxanthines
Theophylline can be used to treat asthma, but that it is not a first-line therapy. Theophylline is a nonselective phosphodiesterase-4 inhibitor that also blocks adenosine receptors to induce smooth muscle relaxation.
The high dosages required to effectively open the airways produce systemic side effects, including convulsions and arrhythmias, as well as gastrointestinal problems and headache.
Rofumilast improves exercise tolerance in COPD patients. Rofumilast is thought to work via histone deacetylation, which produces anti-inflammatory effects.
Thus, it can be prescribed to enhance the anti-inflammatory effects of corticosteroid treatments.
Recall that inflammation is a key part of the pathology of
asthma and
COPD, and promotes infiltration of various immune cells, remodeling, and constriction of the airways. Thus, reducing inflammation is an important component of treating obstructive pulmonary diseases, especially asthma.
Corticosteroids
Corticosteroids, i.e., glucocorticoids, downregulate inflammatory genes to reduce inflammatory cytokines, chemokines, adhesion molecules, and other pro-inflammatory mediators; thus, they reduce the infiltration of inflammatory cells in the airways.
Inhaled corticosteroids such as beclomethasone, are first-line therapy for moderate to severe asthma.
Used alone, they are less effective in patients with COPD, but can be combined with long-acting beta-2-agonist bronchodilators.
Be aware that use of inhalers increases risk of infection in COPD patients.
Oropharyngeal
candidiasis is a common adverse effect in patients using inhaled glucocorticoids.
Oral glucocorticoids, such as prednisone, produce systemic adverse effects, including increased risk of infection, hypertension, osteoporosis, and ocular disorders.
– Thus, they are reserved for
severe exacerbations and/or patients who are unresponsive to other therapies.
Monotherapies
Anti-IgE Antibodies such as omalizumab, bind free IgE and prevent it from binding to mast cell receptors. Thus, omalizumab is given to reduce exacerbations in severe allergic asthma.
Recall that that IgE binding to mast cells triggers release of allergic mediators.
Anti-IL-5 drugs such as mepolizumab, reslizumab, and benralizumab.
Interleukin 5 activates eosinophils and promotes airway inflammation.
Anti-Interleukin-5 receptor blockers and antagonists prevent eosinophil activation and are therefore used as add-on therapies in severe eosinophilic asthma.
Cromolyn reduces mast cell release of inflammatory mediators; though it may be helpful to prevent asthma exacerbations in some patients, it is generally less effective than inhaled corticosteroids.
These drugs can be used to prevent aspirin- and exercise-induced asthma.
Leukotrienes aid in inflammatory cell migration, increase capillary permeability, and induce smooth muscle contraction.
Zileuton is a leukotriene synthesis inhibitor.
Montelukast and
zafirlukast are leukotriene receptor blockers.
Additional COPD Therapies
Smoking cessation is key to slowing progression of the disease.
Mucolytics help break up mucus and facilitate removal for easier breathing.
Oxygen therapy is recommended if oxygen saturation falls below 88%.
Infection prevention is important for reducing harmful exacerbations; patients may be prescribed antibiotics, such as azithromycin, to ward off bacterial infections, and influenza and pneumonia vaccines are recommended.
For full references, please see the full tutorials.
