Theophylline

Theophylline is a methylxantine similar in structure to the dietary xanthine caffeine. Many salts of theophylline have been marketed, the most common being aminophylline, which is the ethylenediamine salt.

Although theophylline has been in clinical use since the 1930’s, its mechanism of action is still uncertain. The bronchodilator effect of theophylline is thought to be mediated through inhibition of phosphodiesterase (PDE). PDE catabolizes cyclic nucleotides in the cell, and its inhibition results in an increase in cAMP and cGMP. Other suggested mechanisms of action include adenosine receptor inhibition. Adenosine receptors on mast cells are activated by adenosine in asthmatic patients, which results in bronchoconstrition by releasing histamine and leukotrienes.

The dose of theophylline required to yield therapeutic concentrations varies among subjects, largely because of differences in clearance. Increased clearance is seen in children and in cigarette and marijuana smokers. Concurrent administration of phenobarbitol and phenytoin increases activity of P-450, which results in increased metabolic breakdown. Reduced clearance is found in liver disease, pneumonia and heart failure. Reduced clearance is also seen with certain drugs, which interfere with the cytochrome P-450 system, such as cimetidine, erythromycin, ciprofloxacin, allopurinol, zileuton, and zafirlukast. Viral infections and vaccinations may also reduce clearance.

Unwanted side effects may be seen at higher plasma concentrations, although they may occur in some patients even at low concentrations. The most common side effects are nausea and vomiting, headache, gastric discomfort, and restlessness.

Category: Pharmacology Notes