Theophylline toxicity

See theophylline for general drug information.

Background

• Primarily used as a bronchodilator, however rarely used now due to better available options
• Also studied for treatment of Acute Mountain Sickness and Contrast-Induced Nephropathy
• PO available as elixer and capsule (12 or 24-hour extended release)
• IV as aminophylline (shorter acting than PO)
• Mechanism of action:
  • Release of endogenous catecholamines → β2 agonism → bronchodilation
  • PDE inhibition → increases cAMP
  • Adenosine antagonist

Clinical Features

• Cardiovascular
  • Sinus Tachycardia
  • Atrial/Ventricular arrhythmias
  • Hypotension (2/2 β2-mediated vasodilation)
• Metabolic
  • Hypokalemia
  • Metabolic Acidosis
  • Hyperthermia
  • Hyperglycemia
• Neurologic
  • Tremor
  • Agitation
  • Seizure
• GI
  • Nausea/Vomiting

Differential Diagnosis

• Beta-2 agonist toxicity
• Sympathomimetic toxicity
• Iron toxicity
• Salicylate toxicity

Evaluation

• Theophylline level
• ECG
• Metabolic panel
• Lactic acid level
• CK

Management

• Supportive care
  • Cardiac monitoring
  • Ondansetron (Zofran) for antiemetic
  • EEG for sedated and paralyzed patients
• Cardiovascular
  • IV Fluids for hypotension
  • Beta blockers for tachyarrhymias
    • Esmolol particularly wise first-line agent
    • Controversial, involve a toxicologist
• GI decontamination (Multidose Activated Charcoal, Whole Bowel Irrigation)
  • Considered in life-threatening overdose
    • contraindications: unsecured airway, nausea, vomiting, ileus, Bowel Obstruction, or need for emergent endoscopy
• Seizures
  • Lorazepam (Ativan) 1st line
  • Phenobarbital if lorazepam ineffective
  • Phenytoin (Dilantin) contraindicated as increases seizure in animal studies
• Dialysis
  • Indicated in seizures, severe arrhythmias
  • Theophylline level >90mcg/ml in acute ingestion
  • Theophylline level >40mcg/ml in chronic ingestion

Disposition

Immediate release

• Home after 6 hours if:
  • nontoxic
  • asymptomatic
  • and, normal vital sign

Sustained release

• Home after 12 hours if:
  • nontoxic
  • asymptomatic
  • and, normal vital sign

See Also

• Toxicology (main)