Theophylline

Theophylline is a naturally occurring alkaloid found in tea and is a methylxanthine similar to caffeine. It is available as a number of different salts, the most common of which are aminophylline (the ethylenediamine) and choline theophyllinate. Theophylline is structurally classified as a methylxanthine. It occurs as a white, odorless, crystalline powder with a bitter taste. Anhydrous theophylline has the chemical name 1H-Purine-2,6-dione,3,7-dihydro-1,3-dimethyl-. The molecular formula of anhydrous theophylline is C7H8N4O2 with a molecular weight of 180.17. (For products containing theophylline monohydrate, substitute the following: The molecular formula of theophylline monohydrate is C7H8N4O2H2O with a molecular weight of 198.18.)

Theophylline is a bronchodilator medicine that opens airways by relaxing the muscles in and around the airways that tighten during an asthma episode. It is one of the most commonly used medications for the treatment of the symptoms of chronic asthma. Its most important actions are to prevent the signs and symptoms of asthma, especially during the night, and to reduce the need for cortisone type medication. It also reduces or prevents symptoms from triggers of asthma such as exercise and allergens. It is a modest bronchodilator relaxing muscles around the airway, allowing air to travel more freely in and out of the lungs.

Theophylline has bronchodilator properties and is used in the treatment of asthma and COAD. Theophylline produces bronchodilatation in a concentration dependent manner and continuous therapy can reduce the symptoms of chronic asthma, reduce the dosage of oral corticosteroids in steroid dependent asthma, and reduce the requirement for symptomatic use of ß2-agonists. However, theophylline also reduces dyspnoea in patients with COAD without alteration of their lung function which could be due to a central, cardiovascular of diaphragmatic effect. Despite theophylline being widely available in a large number of proprietary preparations, little is known about its mode of action. Theophyllines are very popular in the USA and on the continent, but some respiratory physicians in this country still have reservations about its use, mainly because of the high incidence of side effects, particularly at the upper limit of its therapeutic range, and the availability of more potent and less toxic alternatives. However, it still retains an important role in the treatment of acute severe asthma. Theophylline is an antagonist of adenosine at pharmacological doses, but a theophylline analogue, enprofylline, does not antagonise adenosine yet still retains potent bronchodilator activity. Recently, theophylline has also been shown to have some anti-inflammatory activity, inhibiting the activity of CD4 lymphocytes in vitro and mediator release from mast cells, and can inhibit bronchoconstriction produced by exercise and challenge testing. Theophylline is a central nervous system stimulant and can increase minute ventilation in man by stimulation of the medullary respiratory centres. This is thought to be mediated by augmentation of hypoxic ventilatory drive and could account for its effectiveness in reducing apnoeic episodes in premature infants and reducing Cheyne-Stokes respiration. Other effects of theophylline include peripheral and coronary vasodilation, but in the central nervous system, cerebrovascular vasoconstriction and reduced cerebral blood flow. Theophylline also increases catecholamine release from the adrenal medulla, and as a consequence increases heart rate, force of contraction, cardiac output and blood pressure, and also has mild diuretic properties. Clinically, tolerance develops rapidly to the cardiac, diuretic and central stimulant effects of theophylline but not its bronchodilator properties.