Theophylline
Theophylline is a methylxanthine that once was used widely for the treatment of asthma. Intravenous infusions of aminophylline, the ethylenediamine salt of theophylline, are sometimes used to treat bronchospasm, congestive heart failure, and neonatal apnea. Theophylline most commonly is used orally in sustained-release preparations (Theo-Dur, Slo-Phyllin, Theo-24, and many others).
Mechanism of toxicity
The exact mechanism of toxicity is not known. Theophylline is an antagonist of adenosine receptors, and it inhibits phosphodiesterase at high levels, increasing intracellular cyclic adenosine monophosphate (cAMP). It also is known to release endogenous catecholamines at therapeutic concentrations.
Pharmacokinetics. Absorption may be delayed with sustained-release preparations. The volume of distribution is approximately 0.5 L/kg. The normal elimination half-life is 4–6 hours; this may be doubled by illnesses (eg, liver disease, congestive heart failure, influenza) or interacting drugs (eg, erythromycin, cimetidine) that slow hepatic metabolism and may increase to as much as 20 hours after overdose (see also Table II–61).
Toxic dose. An acute single dose of 8–10 mg/kg can raise the serum level by up to 15–20 mg/L, depending on the rate of absorption. Acute oral overdose of more than 50 mg/kg may potentially result in a level above 100 mg/L and severe toxicity.
Clinical presentation. Two distinct syndromes of intoxication may occur, depending on whether the exposure is acute or chronic.
Acute single overdose is usually a result of a suicide attempt or accidental childhood ingestion but also may be caused by accidental or iatrogenic misuse (therapeutic overdose).
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