For theophylline overdose

The primary indication for theophylline is as a controller medication for the treatment of bronchospasm of asthma and COPD. In addition to bronchodilation effects, theophylline dilates pulmonary blood vessels, acts centrally to stimulate respiration, acts as a diuretic, increases gastric acid secretion, and inhibits uterine contractions. Dosing requires the determination of plasma levels with 10 to 20 pg/mL being associated with the least incidence of side effects. Overdose of theophylline can result in a quick onset of ventricular arrhythmias, convulsions, or even death... 

Adverse reactions to drugs differ in both type and incidence in the pediatric population. Because of immature metabolic pathways, infants and children may have different metabolic patterns than adults. This at least partially explains why neonates require lower theophylline serum concentrations for the treatment of neonatal apnea and why the incidence of hepatotoxi-city following acetaminophen overdose is much lower in young children than in adults [44,45]. Antibiotic adverse effects unique to the pediatric population may... 

All new developments have a flip side. The availability of slow-release theophylline has produced new problems for toxicologists. In overdose theophylline is potentially lethal. When a poisoned patient arrives at hospital, a plasma concentration is measured and, for most drugs, it can reasonably be assumed that the absorptive phase would be nearing completion (or can be shortened by gastric aspiration or giving charcoal by mouth). No such... 

Theophylline improves long-term control of asthma when taken as the sole maintenance treatment or when added to inhaled corticosteroids. It is inexpensive, and it can be taken orally. Its use, however, also requires occasional measurement of plasma levels it often causes unpleasant minor side effects (especially insomnia) and accidental or intentional overdose can result in severe toxicity or death. For oral therapy with the prompt-release formulation, the typical dose is 3-4 mg/kg of theophylline every 6 hours. Changes in dosage result in a new steady-state concentration of theophylline in 1-2 days, so the dosage may be increased at intervals of 2-3 days until therapeutic plasma concentrations are achieved (10-20 mg/L) or until adverse effects develop. 

Theophylline, an asthma controller, has a very low safety/therapeutic ratio. One of the first clinical application for HPLC was to titrate theophylline levels in patient blood to avoid toxic overdoses. Blood levels can be controlled by assay at UV, 270 nm, on a C18 column in 7% An/water at pH 4.0 with phosphate buffer. 

Isoniazid Isoniazid is incompatible with sugars. Isoniazid overdose may be severe to fatal, and treatment is symptomatic and supportive, including stomach wash for control of convulsions and treating metabolic acidosis. Administration of pyridoxine and hemodialysis may be needed. Isoniazid interacts with carba-mazepine, phenytoin, diazepam, triazolam, chlorzoxazone, theophylline, ethosux-imide, enflurane, cycloserine, and warfarin. 

Theophylline [the OFF i lin] is a bronchodilator that relieves airflow obstruction in chronic asthma, and decreases the symptoms of the chronic disease. Previously the main-stay of asthma therapy, theophylline has been largely replaced with (3-agonists and corticosteroids. Theophylline is well absorbed by the gastrointestinal tract, and several sustained-release preparations are available. The drug has a narrow therapeutic window, and an overdose of the drug may cause seizures or potentially fatal arrhythmias. Further, theophylline interacts adversely with many drugs. See pp. 450-451 for a description of newly approved drugs, zileuton, zafirlukast, and montelukast. 

Theophylline has a narrow therapeutic index, with 12-25% of overdose patients developing serious or life-threatening symptoms. Age >60 years and chronic use are risk factors for increased morbidity and mortality. 

E. Toxicity The common adverse effects include gastrointestinal distress, tremor, and insomnia. Severe nausea and vomiting, hypotension, cardiac arrhythmias, and convulsions may result from overdosage. Very large overdoses (eg, in suicide attempts) are potentially lethal because of the arrhythmias and convulsions. Beta-blockers are useful antidotes for severe cardiovascular toxicity from theophylline. 

B. Toxicodynamics Toxicodynamics is a term used to denote the injurious effects of toxins, ie, their pharmacodynamics. A knowledge of toxicodynamics can be useful in the diagnosis and management of poisoning. For example, hypertension and tachycardia are typically seen in overdoses with amphetamines, cocaine, and antimuscarinic drugs. Hypotension with bradycardia occurs with overdoses of calcium channel blockers, beta-blockers, and sedative-hypnotics. Hypotension with tachycardia occurs with tricyclic antidepressants, phenothiazines, and theophylline. Hyperthermia is most frequently a result of overdose of drugs with antimuscarinic actions, the salicylates, or sympathomimetics. Hypothermia is more likely to occur with toxic doses of ethanol and other CNS depressants. Increased respiratory rate is often a feature of... 

A. Specific levels. Serum theophylline levels are essential for diagnosis and determination of emergency treatment. After acute oral overdose, obtain repeated levels every 2-A hours single determinations are not sufficient, because continued absorption from sustained-release preparations may result in peak levels 12-16 hours or longer after ingestion. 

Monitor vital signs, ECG, and serial theophylline levels for at least 16-18 hours after a significant oral overdose. 

The effect of phenytoin on theophylline is established and of clinical importance. Patients given both drugs should be monitored to confirm that theophylline remains effective. Ideally the serum levels should be measured to confirm that they remain within the therapeutic range. Theophylline dosage increases of up to 50% or more may be required. Conversely, patients should be monitored for signs of toxicity and theophylline levels should be checked in patients who stop phenytoin. The effect of theophylline on phenytoin is not established and the documentation is limited. It may be prudent to monitor phenytoin levels as well. Separating the doses appears to minimise any interaction. Note that theophylline itself can cause seizures, although mostly in overdose, and should be used with caution in patients with epilepsy. 

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