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Clinical Pharmacology of Oral Maintenance Therapies for Obstructive Lung Diseases.

Although inhaled therapies are typically preferred for the maintenance treatment of obstructive lung diseases, oral drug therapies can also play valuable roles. The most commonly used oral agents are phosphodiesterase inhibitors, theophylline, macrolides, leukotriene modifiers, and mucoactive agents. Advantages of these oral agents include the unique pharmacologic mechanisms of action, the avoidance of the challenges of proper inhalational lung administration, and, in most instances, relative drug cost. For many of these agents, anti-inflammatory or immunomodulatory effects are the predominant pharmacologic mechanism that each provides clinical benefit, with the exception of guaifenesin. In addition, theophylline, leukotriene modifiers, chronic macrolides, phosphodiesterase inhibitors, and N-acetylcysteine have been shown to decrease exacerbations in obstructive lung disease. Fairly rapid bronchodilation occurs with the phosphodiesterase inhibitors, theophylline, and leukotriene modifiers, although less than that achieved with inhaled therapies. The clinical roles of phosphodiesterase inhibitors, specifically roflumilast, and macrolides continues to be defined today, whereas the roles theophylline and leukotriene modifiers have probably been largely delineated. Azithromycin is the principal macrolide used chronically for obstructive lung diseases, especially COPD. Although guaifenesin is used widely, its effectiveness is unclear, whereas N-acetylcysteine currently has strong evidence supporting a decreased risk of COPD exacerbations. Mucolytic agents like N-acetylcysteine are used more widely outside the United States in obstructive lung diseases.

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