Theophylline & Caffeine Toxicity

Methylxanthines including theophylline and caffeine are nonselective adenosine receptor antagonists

In overdose, toxicity results from the release of endogenous catecholamines with beta-1- and beta-2-adrenergic stimulation

Theophylline

• May cause intoxication after an acute single overdose or

• Intoxication may occur as a result of chronic accidental repeated overmedication or reduced elimination resulting from liver dysfunction or interacting drug (eg, cimetidine, erythromycin)

• Usual serum half-life of theophylline is 4–6 h; this may increase to > 20 h after overdose

Caffeine in energy drinks or herbal or dietary supplement products can produce similar toxicity

Mild intoxication

• Nausea

• Vomiting

• Tachycardia

• Tremulousness

Severe intoxication (serum levels > 100 mg/L [555 mcmol/L])

• Ventricular and supraventricular tachyarrhythmias

• Hypotension

• Seizures

Status epilepticus is common and often intractable to usual anticonvulsants

Symptoms may be delayed for hours after acute ingestion, especially if a sustained-release preparation was taken

Serious toxicity may develop at lower levels (40–60 mg/L [222–333 mcmol/L]) with chronic intoxication

Serum theophylline concentration

Hypokalemia, hyperglycemia, and metabolic acidosis are common after acute overdose

Activated charcoal

• Give after acute ingestion

• 60–100 g orally or via gastric tube, mixed in aqueous slurry

• Do not use for comatose or convulsing patients unless it can be given by gastric tube and airway is protected by a cuffed endotracheal tube

• Repeat doses may enhance gut decontamination and elimination by "gut dialysis"

Consider whole-bowel irrigation for large ingestions of sustained-release preparations

Indications for hemodialysis

• Status epilepticus

• Markedly elevated serum theophylline levels (eg, > 100 mg/L [555 mcmol/L] after acute overdose or possibly for levels > 60 mg/L [333 mcmol/L] with chronic intoxication)

Treatment of seizures

• Lorazepam, 2–3 mg intravenously

• Diazepam, 5–10 mg intravenously

• Phenobarbital, 10–15 mg/kg intravenously

• Phenytoin is not effective

Hypotension and tachycardia may respond to beta-blocker therapy even in low doses

• Esmolol, 25–50 mcg/kg/min by intravenous infusion

• Propranolol, 0.5–1.0 mg intravenously