Theophylline seizures caused

A. Control of tonic-clonic seizures and status epilepticus, generally as a seconder third-line agent after diazepam or phenytoln have been tried. Note For treatment of dmg-Induced seizures, especially seizures caused by theophylline, phenobarbital Is often tried before phenytoln. 

Concurrent use of the fluoroquinolones with theophylline causes an increase in serum theophylline levels. When used concurrently with cimetidine, the cimetidine may interfere with the elimination of the fluoroquinolones. Use of the fluoroquinolones with an oral anticoagulant may cause an increase in the effects of the oral coagulant. Administration of the fluoroquinolones with antacids, iron salts, or zinc will decrease absorption of the fluoroquinolones. There is a risk of seizures if fluoroquinolones are given with the NSAIDs. There is a risk of severe cardiac arrhythmias when the fluoroquinolones gatifloxacin and moxifloxacin are administered with drains that increase the QT interval (eg, quini-dine, procainamide, amiodarone, and sotalol). 

Isolated seizures that are not epilepsy can be caused by stroke, central nervous system trauma, central nervous system infections, metabolic disturbances (e.g., hyponatremia and hypoglycemia), and hypoxia. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures I or epilepsy. Medications can also cause seizures. Some drugs that are commonly associated with seizures include tramadol, bupropion, theophylline, some antidepressants, some antipsy-chotics, amphetamines, cocaine, imipenem, lithium, excessive doses of penicillins or cephalosporins, and sympathomimetics or stimulants. 

Side effects are usually associated with the increasing serum concentration of theophylline and includes nausea, vomiting, headache, insomnia, tachypnea, epigastric pain, palpitation, hypotension, irritability. Higher doses can cause persistent vomiting, cardiac arrhythmias, intractable seizures, tachycardia. Other side effects include alopecia, hyperglycemia, inappropriate ADH syndrome, rash. 

Theophylline should be used only where methods to measure theophylline blood levels are available because it has a narrow therapeutic window, and its therapeutic and toxic effects are related to its blood level. Improvement in pulmonary function is correlated with plasma concentrations in the range of 5-20 mg/L. Anorexia, nausea, vomiting, abdominal discomfort, headache, and anxiety occur at concentrations of 15 mg/L in some patients and become common at concentrations greater than 20 mg/L. Higher levels (more than 40 mg/L) may cause seizures or arrhythmias these may not be preceded by gastrointestinal or neurologic warning symptoms. 

An example of a potentially important drug interaction is that which occurs when fluvoxamine is given along with theophyllin (Figure 6—13). In that case, the theo-phyllin dose must be lowered or else the blood levels of theophyllin will rise and possibly cause side effects, even toxic side effects such as seizures. The same may occur with caffeine. Fluvoxamine also affects the metabolism of atypical anti-psychotics. 

Seizures, muscular hyperactivity, and rigidity may result in death. Seizures may cause pulmonary aspiration, hypoxia, and brain damage. Hyperthermia may result from sustained muscular hyperactivity and can lead to muscle breakdown and myoglobinuria, renal failure, lactic acidosis, and hyperkalemia. Drugs and poisons that often cause seizures include antidepressants, theophylline, isoniazid (INH), diphenhydramine, antipsychotics, cocaine, and amphetamines. 

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. 

Fluvoxamine administered with either caffeine or theophylline can thus cause jitteriness, excessive stimulation, or rarely seizures, so concomitant use should proceed cautiously... 

Sympathomimetic syndromes include tachycardia, hypertension, hyperthermia, sweating, mydriasis, hyperreflexia, agitation, delusions, paranoia, seizures and cardiac arrhythmias. These are commonly caused by amphetamine and its derivatives, cocaine, proprietary decongestants, e.g. ephedrine, and theophylline (in the latter case, excluding psychiatric effects). 

Concomitant treatment with fluvoxamine may cause a marked elevation in plasma theophylline levels associated with signs of theophylline toxicity, including ventricular tachycardia, anorexia, nausea, and seizures. 

A a X 0 Q, 1 W s o a (D CQ PO/PR. Well absorbed, liver metabolism, kidney excretion. Dozens of standard and long-acting preparations available. Patients with seizure disorder, cardiovascular disorder or peptic ulcer disease. Sympathomimetics T risk of heart and CNS toxicity. Cimetidine, oral contraceptives and several antibiotics t half-life of theophylline - thus T toxicity. Phenobarbital and phenytoin induce metabolism of theophylline, thus i half-life. Dehdydration results from t diuresis with concurrent use of furosemide. Warn patients doubling a dose, even if one is missed, is very dangerous. Intoxication may cause seizures. Treat overdose with ipecac, activated charcoal, and a cathartic. 

Information seems to be limited to the reports cited so that the general importance is uncertain. Concurrent use need not be avoided, but it would be prudent to check that the serum concentrations of each drug (and their effects) do not become subtherapeutie. Note that theophylline should be used with caution in patients with epilepsy as it can cause seizures, although this is usually a sign of toxicity. 

A series of 8 patients with severe ehronic asthma found that troleandomycin 250 mg four times daily caused an average reduction in the clearance of theophylline (given as intravenous aminophylline) of 50%. One patient had a theophylline-induced seizure after 10 days, with a serum theophylline level of 43 mg/mL (reference range 10 to 20 mg/L). The theophylline half-life in this patient had increased from 4.6 to 11.3 hours. Other studies in healthy subjects and patients given oral theophylline with troleandomycin have also found reductions in theophylline clearance and marked rises in serum theophylline levels and half-life, even at low troleandomycin doses. ... 

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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