Introduction
Background
Theophylline has indications for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Medication, diet, and underlying diseases can alter its narrow therapeutic window. Adverse effects can be evident at therapeutic serum levels.
Pathophysiology
Theophylline is absorbed rapidly after oral administration. Peak serum levels occur in 90-120 minutes. Fasting or large volumes of fluid enhance absorption. Enteric-coated and sustained-release tablets have a delayed absorption. Intravenous aminophylline reaches peak serum levels in 30 minutes.
Theophylline is 60% protein bound and has a distribution volume of 0.5 L/kg. Therapeutic serum levels range from 10-20 mcg/mL. Toxic levels are considered to be higher than 20 mcg/mL; however, adverse effects may be evident within the normal therapeutic range.
Theophylline is eliminated by the hepatic cytochrome P-450 system (85-90%) and by urinary excretion (10-15%). The half-life is 4-8 hours in young adults and is shorter in children and smokers. Diet, cardiac or liver disease, tobacco use, and medications affecting the cytochrome P-450 system can affect the half-life.
Theophylline affects the cardiovascular (CV), neurological, GI, and metabolic systems. Hypokalemia, hyperglycemia, hypercalcemia, hypophosphatemia, and acidosis commonly occur after an acute overdose.
Frequency
United States
The 2002 annual report of the American Association of Poison Control Centers' Toxic Exposure Surveillance System documented 1030 exposures to theophylline, with 170 in children younger than 6 years and 757 in persons older than 19 years. Of the 585 theophylline exposures treated in health care facilities, 39 were reported to have major adverse outcomes and 8 fatalities were noted. The documented toxic exposures have decreased markedly over the past decade as the utilization of theophylline for the management of asthma has diminished.
Race
No scientific data have demonstrated that outcomes of theophylline toxicity are dependent on race.
Sex
No scientific data have demonstrated that outcomes of theophylline toxicity are dependent on sex.
Clinical
History
- Symptomology correlates better with single acute ingestions than with chronic overexposures. Symptoms of acute theophylline overdose are as follows:
- Nausea
- Vomiting
- Abdominal pain
- Mild metabolic acidosis
- Hypokalemia
- Hypophosphatemia
- Hypomagnesemia
- Hyperglycemia
- Tachycardia
- Chronic theophylline overdose has minimal GI signs or symptoms.
- Seizures, hypotension, and significant dysrhythmias usually are not observed until serum levels approach 80 mcg/mL.
- Seizures are more common with acute overdose than with chronic overdose and may develop at lower serum concentrations (40-60 mcg/mL).
- Cardiac dysrhythmias are more common following an acute overdose than chronic overdose.
Physical
- Cardiovascular
- Sinus tachycardia (most common)
- Atrial fibrillation
- Atrial flutter
- Supraventricular tachycardia (SVT)
- Multifocal atrial tachycardia
- Ventricular tachycardia
- Hypotension (severe overdoses)
- Ventricular fibrillation
- Pulseless electrical activity (PEA)
- Cardiac arrest
- Neurological
- Tremors (most common)
- Restlessness
- Agitation
- Hallucinations
- Headaches
- Irritability
- Seizures (Persistent seizures may occur with serum levels >25 mcg/mL.)
- Gastrointestinal
- Nausea
- Vomiting
- Abdominal cramps
- Diarrhea
Causes
- Chronic toxicity
- Drug interactions (eg, ethanol [ETOH], cimetidine, oral contraceptives, allopurinol, macrolide, quinolone antibiotics)
- Liver disease
- Congestive heart failure
- Febrile viral upper respiratory illness
- Acute toxicity
- Accidental overdose
- Intentional overdose
More on Toxicity, Theophylline |
 Overview: Toxicity, Theophylline |
| Differential Diagnoses & Workup: Toxicity, Theophylline |
| Treatment & Medication: Toxicity, Theophylline |
| Follow-up: Toxicity, Theophylline |
| References |
| Next Page » |
References
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Gaudreault P, Harwood-Nuss. Methylxanthines, Toxicology. In: Clinical Practice of Emergency Medicine. 4th ed. 2005:1649-1652.
Henderson A, Wright DM, Pond SM. Management of theophylline overdose patients in the intensive care unit. Anaesth Intensive Care. Feb 1992;20(1):56-62. [Medline].
Kallstrom TJ. Evidence-based asthma management. Respir Care. Jul 2004;49(7):783-92. [Medline].
Kearney TE, Manoguerra AS, Curtis GP, Ziegler MG. Theophylline toxicity and the beta-adrenergic system. Ann Intern Med. Jun 1985;102(6):766-9. [Medline].
Marshall H, Emerman CL, Tintinalli J. Theophylline, Toxicology and Pharmacology. In: Emergency Medicine, A Comprehensive Study Guide. 6th ed. 2004:1098-1101.
Medical Economics Staff. Drugs. In: Physician's Desk Reference. Medical Economics Co;1997.
Micromedex. Theophylline. In: Micromedex. 1974-2006:36.
Seneff M, Scott J, Friedman B, Smith M. Acute theophylline toxicity and the use of esmolol to reverse cardiovascular instability. Ann Emerg Med. Jun 1990;19(6):671-3. [Medline].
Further Reading
Keywords
theophylline overdose, acute theophylline overdose, chronic theophylline intoxication, methylxanthine, asthma treatment, chronic obstructive pulmonary disease treatment, COPD treatment, theophylline adverse affects, theophylline prescription, methylxanthine derivative, 1, 3-dimethylxanthine, smooth muscle relaxant, diuretic, cardiac stimulant, vasodilator, angina pectoris treatment, peripheral vascular disease treatment, bronchial asthma treatment
