Current Status of the Use of Theophyllines in Children

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Abstract
Theophyllines have gone through cycles of popularity and unpopularity as therapeutic agents since they were first used for relief of asthma in 1936. By competitive inhibition of the enzyme phosphodiesterase, they prevent the breakdown of cyclic 3',5'—AMP (adenosine monophosphate) to 5'—AMP and act synergistically with beta-adrenergic agents to increase the intracellular concentration of 3' 5 cyclic AMP. In lung tissue cyclic 3',5'—AMP leads to relaxation of bronchial smooth muscle, perhaps by direct effect or perhaps by suppression of local histamine release.1 Theophyllines are of particular value in the epinephrine-resistant patient with asthma. Toxic effects of theophyllines are related to serum theophylline levels and represent intensifications of pharmacologic effects. They include insomnia, irritability, restlessness, tremors, convulsions, flushing, tachycardia and other cardiac arrhythmias, hypotension or hypertension, abdominal pain, anorexia, nausea, vomiting, hematemesis, dehydration, and albuminuria. Gastrointestinal side effects are centrally mediated and are not prevented or ameliorated by giving theophyllines rectally or intravenously.2 In the 1960's many physicians virtually discontinued the use of aminophylline, which is 80% theophylline by weight and hydrolyzed to free theophylline in vivo, because of numerous reports of deaths following its administration.3-6 Most of the childhood deaths attributable to this drug occurred after use of rectal suppositories.5,6 Absorption from the suppository base is slow and unpredictable,7 and cumulative effects often occur. Administration of excessive amounts of theophylline or aminophylline (or administration of the latter by rapid intravenous injection, injection into a central venous catheter,8 or administration to patients with compromised cardiovascular or renal systems3,4) has also been associated with deaths, more often in adults than in children. Idiosyncratic reactions are exceptionally rare.

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