Methylated xanthines theophylline and aminophylline

Theophylline is inferior to b-agonists as first-line treatment of acute asthmatic attacks, although it may have a synergistic action with b-agonists. It can be combined with ethylenediamine (aminophylline) to become 20 times more soluble than theophylline alone.

The mode of action of theophylline is unclear, but it is known to inhibit the enzyme phosphodiesterase to decrease the metabolism of cyclic AMP. The dose necessary for this action is much higher than that used clinically. Theophylline has a direct relaxant effect on bronchial smooth muscle, a mild inotropic effect, and a diuretic effect, and it delays the onset of diaphragmatic muscle fatigue. It is available intravenously (aminophylline) and orally (theophylline) in preparations with different lengths of action.

The onset of action by the intravenous route is slower than that of the b-agonists because of the need to deliver it over 20 to 30 min. Side-effects include nausea and vomiting, central nervous system irritability and seizures, flushing, hypotension, and a variety of tachyarrhythmias including cardiac arrest. Seizures due to theophylline toxicity are often difficult to treat. The ethlyenediamine component of aminophylline can cause urticaria, erythema, and exfoliative dermatitis. Cautions include liver disease, epilepsy, cardiac disease, and pregnancy.

Therapeutic levels of theophylline are quoted as 10 to 20 pg/ml, and these should be monitored in the critically ill. Rarely, serious side-effects do still occur in this range, and levels should be monitored in those who have previously received theophylline preparations or who are given a maintenance infusion.

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