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Methylxanthine toxicity can be associated with life-threatening seizures and cardiac arrhythmias.
Predictors of toxicity include hypokalaemia, lactic acidosis and serum theophylline concentration.
Early identification of high-risk patients allows the institution of enhanced elimination techniques before life-threatening complications develop.
Theophylline, a methylxanthine derivative related to caffeine, can result in potentially life-threatening overdose presentations to the emergency department (ED). The decline in theophylline use has closely mirrored the emergence of caffeine overdose.
Therapeutic blood concentrations of theophylline are generally regarded as being between 10 and 20 mg/L. A single ingestion of more than 10 mg/kg of theophylline by an adult is capable of producing a blood concentration above this range.
Theophylline is well absorbed orally, with a bioavailability of almost 100%. The rate of absorption depends on the pharmaceutical formulation. The most commonly prescribed preparations are sustained-release, and following overdose of these preparations, peak absorption may be delayed up to 15 hours.
Once absorbed, theophylline is rapidly distributed. It is metabolized via the cytochrome P450 system to produce active and inactive metabolites. The rate of metabolism is extremely variable and exhibits saturable kinetics. At higher doses of theophylline, relatively small increments in dose are associated with disproportionate increases in serum concentration. In cases of severe intoxication, endogenous elimination of theophylline is very slow. Only about 10% of absorbed theophylline is excreted unchanged in the urine.
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