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XANTHINES

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Theophylline, theobromine, and caffeine are methylxanthines.

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Theophylline was once widely used for the management of asthma and chronic obstructive pulmonary disease, and continues to be used for apnea of prematurity. Caffeine is the most widely used psychoactive drug in the world, and is consumed primarily from beverages such as coffee, tea, and energy drinks, but is also contained in medications and dietary supplements. Caffeine is used medically in the management of apnea of prematurity, and as an analgesic adjunct.

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Clinical Features

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Methylxanthine toxicity can cause life-threatening cardiac, neurologic, and metabolic abnormalities. Even therapeutic concentrations of theophylline can cause significant side effects in some individuals. Elderly patients with concomitant medical problems are more susceptible to life-threatening toxicity during chronic therapeutic use than are younger patients with acute overdose.

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Cardiac side effects usually include sinus tachycardia, and may include atrial and/or ventricular dysrhythmias. Ventricular dysrhythmias are more common with severe toxicity, chronic toxicity, in the elderly, and those with underlying cardiac dysfunction. Hypotension may also occur as a result of peripheral Beta 2 induced vasodilation.

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Neurologic toxicity includes agitation, headache, irritability, sleeplessness, tremors, hallucinations, and seizures. Methylxanthine-induced seizures can be severe and refractory to standard treatment.

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Metabolic side effects include hypokalemia, hyperglycemia, and metabolic acidosis. Rhabdomyolysis has been reported with theophylline and caffeine overdose. Compartment syndrome resulting from an unclear etiology is also a rare, but well-described occurrence in theophylline toxicity. Gastrointestinal (GI) effects commonly include nausea and vomiting. Nausea and vomiting are often severe, and poorly responsive to less potent antiemetics.

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Diagnosis and Differential

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Therapeutic serum theophylline levels of 20 μg/mL can produce toxic effects. In acute poisoning, severity of symptoms typically correlates with serum concentration, but with chronic or acute on chronic toxicity symptom severity correlates more poorly with concentration.

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In cases of chronic or acute on chronic toxicity, life-threatening side effects can occur with little warning and before lesser symptoms manifest. Smoking cessation, cirrhosis, and numerous medications, such as cimetidine and erythromycin, increase the half-life of theophylline and increase risk of chronic toxicity. Investigations recommended for theophylline or caffeine toxicity includes serial measurement of the serum theophylline or caffeine concentration, serum electrolytes, and a 12-lead ECG. The differential diagnosis includes other sympathomimetic overdose (e.g., amphetamines, cocaine) as well as anticholinergic toxicity.

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Emergency Department Care and Disposition

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Treatment of methylxanthine poisoning consists of stabilization, gastric decontamination and elimination, treatment of life-threatening toxic effects, and, in severe cases, hemoperfusion or dialysis.

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  1. Table 107-1 lists appropriate methods of GI decontamination and elimination in methylxanthine toxicity.

  2. Place all patients on cardiac monitors and establish intravenous (IV) or intraosseous (IO) access.

  3. Treat nausea and vomiting with ondansetron 4 to 8 mg IV or PO (0.1 to 0.15 mg/kg). Consider ranitidine for gastric hypersecretion but avoid cimetidine, which ...

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