19.3: Antiasthma Drugs: Methylxanthines

Theophylline, a member of the methylxanthine class of bronchodilators, has long been used in asthma management. While its exact mechanism of action is not fully understood, it is believed to have multiple effects on various cellular processes.

Theophylline is thought to inhibit phosphodiesterase enzymes, increasing intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). This rise in cAMP and cGMP concentrations stimulates cardiac function, relaxes smooth muscle, and reduces inflammation in specific cells. Another proposed mechanism involves the inhibition of adenosine receptors on cell surfaces. By blocking these receptors, theophylline increases the activity of adenylyl cyclase, which results in bronchodilation.

Theophylline is typically administered orally as a sustained-release preparation to ensure a prolonged therapeutic effect. In certain situations, a related drug called aminophylline may be administered through slow intravenous injection.

While theophylline can provide therapeutic benefits, it is essential to know its adverse effects. They can be mild, such as nausea, vomiting, abdominal discomfort, and headache, to more severe effects like seizures or arrhythmias. Monitoring blood levels of theophylline is crucial to prevent toxicity. In recent years, theophylline has been replaced primarily by β₂ agonists and corticosteroids as the cornerstone of asthma treatment. These newer medications offer improved efficacy and safety profiles. As a result, the U.S. Food and Drug Administration (FDA) no longer recommends using theophylline for severe asthma exacerbations known as status asthmaticus.

Methylxanthines, such as theophylline, act as bronchodilators to manage asthma.

Theophylline's exact mechanism of action is complex, potentially involving phosphodiesterase enzyme inhibition, elevating intracellular cAMP and cGMP levels. This action stimulates cardiac function, relaxes airway smooth muscle, and reduces inflammation.

Another suggested mechanism is via adenosine receptor inhibition on cell surfaces to increase adenylyl cyclase activity, leading to bronchodilation.

Theophylline is typically administered orally as a sustained-release formulation to ensure a prolonged therapeutic effect. Aminophylline, a combination of theophylline and ethylenediamine, is administered intravenously in specific cases.

Despite the therapeutic benefits, theophylline yields side effects ranging from mild symptoms such as nausea, vomiting, abdominal discomfort, and headache to more severe effects such as seizures or arrhythmias.

Due to its narrow therapeutic window and adverse effects, theophylline has been replaced by β₂-agonists and corticosteroids. As a result, the FDA no longer recommends theophylline for status asthmaticus.