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Theophylline, theobromine, and caffeine are methylxanthines. Theophylline was once widely used for the management of asthma and chronic obstructive pulmonary disease. Theobromine is found in chocolate and cocoa as well as numerous “energy drinks.” Caffeine is the most commonly used psychoactive drug in the world and can be legally purchased by children. It is used medically in the management of apnea of prematurity, as an analgesic adjunct, and in some over-the-counter weight loss preparations.

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Nicotine is rapidly absorbed through the lungs, mucous membranes, intestinal tract, and skin. Once absorbed, it binds to nicotinic receptors throughout the body including the central nervous system, autonomic system, and neuromuscular junction.

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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 with chronic use than are younger patients with acute overdose.

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Cardiac side effects include sinus tachycardia, premature atrial contractions, atrial flutter, and atrial fibrillation. Ventricular arrhythmias are more common with chronic toxicity, in the elderly, and those with underlying cardiac dysfunction. Hypotension may also occur.

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

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Metabolic side effects include hypokalemia, hyperglycemia, and metabolic acidosis. Rhabdomyolysis has been reported with theophylline and caffeine overdose. Gastrointestinal effects commonly include nausea and vomiting.

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Nicotine toxicity affects the GI, neurologic, cardiovascular, and respiratory systems. Nausea, vomiting, bradycardia, arrhythmias, hypoventilation, coma, and seizures can occur. In severe poisoning, nicotine can result in paralysis and respiratory arrest. Table 107-1 lists the clinical effects of nicotinic receptor stimulation.

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Table 107-1 Clinical Effects of Nicotine Toxicity
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Therapeutic serum theophylline levels of 10 to 15 micrograms/mL can produce toxic effects and the severity of symptoms may not correlate with serum levels, especially in the setting of chronic use. 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 may precipitate toxicity. Laboratory evaluation for theophylline toxicity includes serum theophylline level, and electrolytes and an ECG should be obtained in cases of all methylxanthine toxicity. The differential diagnosis includes other stimulant drug overdose (eg, amphetamines, cocaine) and electrolyte abnormalities.

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Diagnosis of acute nicotine toxicity is largely based on history and physical examination. Qualitative urine toxicological screen is of little value. ...

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