theophylline - History, Side effects

An alkaloid, in the same chemical family as caffeine and theobromine, found in a variety of plants, including tea. It is used in the treatment of asthma, and is sometimes used as a mild diuretic. Like caffeine, theophylline is a mild stimulant.

Theophylline is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names.

The main actions of theophylline are:

relaxing of bronchial smooth muscle positive inotropic (increasing heart muscle contractility and efficiency) positive chronotropic (increasing heart rate) increase of blood pressure increase of renal blood flow some anti-inflammatory effects

History

Theophylline was first extracted from tea leaves around 1888 by the German biologist Albrecht Kossel.

Side effects

The use of theophylline is complicated by the fact that it interacts with various drugs, chiefly cimetidine and phenytoin, and that it has a narrow therapeutic index, so its use must be monitored to avoid toxicity.

The main therapeutic uses of theophylline are:

chronic obstructive diseases of the airways chronic obstructive pulmonary disease (COPD) bronchial asthma.

Theophylline has been shown to inhibit TGF-beta mediated conversion of pulmonary fibroblasts into myofibroblasts in COPD and asthma via cAMP-PKA pathway and suppresses COL1 mRNA which codes for the protein collagen. (Yano, Biochem and Biophys Res Comm V341-3, 2006)

It has been shown that theophylline may reverse the clinical observations of steroid insensitivity in patients with COPD and asthmatics who are active smokers (a condition resulting in oxidative stress) via a distinctly separate mechanism. Theophylline in vitro can restore the reduced HDAC (histone deacetylase) activity that is induced by oxidative stress (i.e. It has recently been shown that the oxidative stress associated with cigarette smoke can inhibit the activity of HDAC2, thereby blocking the anti-inflammatory effects of corticosteroids.) Thus theophylline could prove to be a novel form of adjunct therapy in improving the clinical response to steroids in smoking asthmatics.