METHYLXANTHINES

The three important methylxanthines are theophylline, theobromine, and caffeine. The theophylline preparations most commonly used for therapeutic purposes is aminophylline (theophylline plus diethylamine).

Mechanism of Action

1. Competitively inhibit phosphodiesterase (PDE) enzyme leading to increased cAMP level.
2. They competitively inhibit the action of adenosine on adenosine (A1 and A2) receptors (adenosine has been shown to cause contraction of isolated airway smooth muscle and to provoke histamine release from airway mast cells.
3. Inhibit the release of histamines and leukotriens from the mast cells

Of the three natural xanthines, agents theophylline is most selective in its smooth muscle effect, while caffeine has the most marked central effect.

Pharmacokinetics

Only slightly soluble in water so has been administered as several salts containing varying amounts of theophylline base. Most preparations are well absorbed from gastro intestinal tract and metabolized by liver. Doses should be decreased in cases of liver disease and heart failure.

Adverse Effects:

Anorexia, nausea vomiting, abdominal discomfort, headache, anxiety, insomnia, seizures, arrhythmias.

Theophylline is now largely reserved for patients in whom symptoms remain poorly controlled despite the combination of regular treatment with an inhaled anti- inflammatory agent and as needed use of a ß2 agonist.