Clinical Pharmacology of Oral Maintenance Therapies for Obstructive Lung Diseases

Abstract

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.

Automated conflict resolution for patients with multiple morbidity being treated using more than one set of single condition clinical guidance: A case study

“…activity in COPD patients). We have also highlighted the conflict between the drugs prescribed for the two conditions, in this excerpt we draw attention to the conflict between prescribing roflumilast used in treating COPD to enhance the anti-inflammatory properties of corticosteroids and mucolytics (that thin mucus making it easier to expectorate) and Non-steroidal anti-inflammatory drugs (NSAID's) which are used to mitigate pain and swelling in those with OA [28,38].…”

Empirical Treatment and Prevention of COVID-19

“…Theophylline at low doses (100 - 200 mg twice daily), the medicine applied to the treatment of asthma for a long time, can be administered safely. It can protect alveolar epithelium with the suppression of cytokine-inducible nitric oxide synthase (NOS) and raising intracellular cyclic adenosine monophosphate [ 19 ]. Macrolide antibiotics including azithromycin cause few side effects and their early application can support epithelial cells for some time [ 20 ].…”

Systemic Medications in Chronic Obstructive Pulmonary Disease

“…Theophylline is a xanthine structurally similar to caffeine that was initially developed for asthma in the late 1930's, at a time when COPD was not even well recognized [17][18][19]. Its main mechanisms of action are adenosine receptors (A1 and A2) inhibition (high potency at therapeutic concentrations) and (weak) phosphodiesterase (PDE) 3 and 4 selective inhibition at higher and poorly tolerated concentrations [20].…”

“…cAMP is also involved in smooth muscle relaxation, but the bronchodilator effect of roflumilast at therapeutic concentrations is limited. In animal models, roflumilast prevents cigarette smoke-induced lung inflammation and emphysema [18].…”