Pharmacologic Treatment
Pharmacologic approaches to pulmonary disease include medications that are specific for the particular condition and medications that improve the patient’s symptoms and functional status. Specific medications directly alter the pathophysiologic mechanisms underlying pulmonary disease. Some examples include cyclophosphamide for granulomatosis with polyangiitis, corticosteroids for sarcoidosis, and plasmapheresis in combination with immunosuppressive drug therapy for Goodpasture syndrome.
Symptomatic medications are designed to reduce the obstructive or restrictive components affecting the patient’s lung function. Medications used to treat symptomatic bronchospastic airway obstruction include bronchodilators and inhibitors of inflammation (Fig 7-1), as well as antibiotics for infection-precipitated airway closures.
Bronchodilators, which include theophylline, β-adrenergic agonists, and anticholinergics, act primarily by relaxing the tracheobronchial smooth muscle. β-Adrenergic agonists activate bronchial smooth muscle, resulting in bronchodilation. The selective β2-adrenergics, which have greater bronchodilatory effect and less cardiostimulatory effect, are commonly used, often in metered-dose inhalers (they can also be administered orally or parenterally). These drugs have replaced the nonselective β-adrenergic agents such as isoproterenol. The short-acting β2-agonists include fenoterol, salbutamol, and isoetharine. These drugs differ in time of onset of action and duration of action. For example, the onset of action of isoetharine is within 1–3 minutes, and its duration is 60–90 minutes. Common long-acting β2-agonists include formoterol and salmeterol. Salmeterol, a particularly long-acting β2-adrenergic, is helpful in maintenance treatment of asthma; it should not be used for acute exacerbations. Although epinephrine causes predominantly β-adrenergic stimulation in the lungs, it also causes peripheral α-adrenergic stimulation, resulting in vasoconstrictive hypertension and tachycardia. Epinephrine is most often administered subcutaneously to help control an acute asthma attack.
Anticholinergic agents directly relax smooth muscle by competing for acetylcholine at muscarinic receptors. Atropine and similar agents have been replaced by poorly absorbing atropinic congeners such as ipratropium bromide, oxitropium bromide, and tiotropium bromide. These inhalation agents have few systemic and minimal cardiac effects. They have an additive bronchodilator effect when combined with submaximal doses of β-adrenergic agonists.
Inhibitors of inflammation include corticosteroids, leukotriene inhibitors, mast-cell stabilizers (cromolyn), and immunosuppressive agents. Corticosteroids not only suppress inflammation of the bronchioles but also potentiate the bronchodilator response to β-adrenergic receptors. Inhaled corticosteroids can be used for an extended period to reduce bronchial hyperreactivity; they are not used to manage acute attacks. Systemic corticosteroids are highly effective in managing acute episodes, but because of the potential adverse effects associated with their use, they should be used only when necessary for serious flare-ups. Leukotriene inhibitors suppress the effects of inflammatory mediators. They are especially useful for prophylaxis and long-term maintenance therapy in asthma. Cromolyn prevents the release of chemical mediators from mast cells in the presence of IgE antibody and the specific antigen. Immunotherapy has been shown to be helpful for asthma triggered by a defined antigen.
Asthma treatment should be tailored to disease severity. Medication doses should be adequate to control symptoms rapidly and should later be reduced to the minimal level required to maintain control. The goals of therapy should include prevention of symptoms, reduction in frequency and severity of exacerbations, maintenance of normal (or near-normal) pulmonary function, maintenance of normal activity levels, and minimization of medication adverse effects. Maintenance medications include inhaled corticosteroids, cromolyns, leukotriene inhibitors, long-acting β2-agonists, anticholinergic agents, and oral corticosteroids. Appropriately used supplemental oxygen increases survival among patients with chronic respiratory failure and has a beneficial effect on pulmonary arterial pressure, polycythemia, exercise capacity, lung mechanics, and mental state.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.