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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the effect of phenobarbital sodium therapy and subependymal intraventricular hemorrhage (SEp-IVH) on the theophylline requirement of premature infants suffering with apnea and seizure activity, we compared three groups of patients as follows: group 1, those with apnea of prematurity (ten patients); group 2, those with apnea and SEp-IVH (ten patients); and group 3, those with apnea, SEp-IVH, and seizure activity for which they were receiving phenobarbital therapy (nine patients). Patients in groups 1 and 2 required lower dosages and blood levels of theophylline to control their apnea than did those in group 3, who required higher dosages and blood levels of methylxanthines. Theophylline dosages and blood levels did not significantly differ between groups 1 and 2. In group 3, the theophylline requirement for control of apnea was significantly increased after initiation of phenobarbital therapy. There seems to be a direct correlation between the increased requirement for theophylline and concomitant phenobarbital administration. The data suggest that phenobarbital increases theophylline requirement when treating neonatal apnea.
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PMID:Phenobarbital increases the theophylline requirement of premature infants being treated for apnea. 378 91

Theophylline, the bronchodilating agent, can cause life-threatening, generalized seizures when plasma concentrations exceed the usual therapeutic concentration range. However, the plasma concentrations of theophylline associated with this neurotoxic effect vary widely between patients. To determine the reasons for the wide variation, and thereby to facilitate prevention or early treatment of theophylline-induced neurotoxicity, an animal model of theophylline-induced seizures was developed and has now been used to determine the effect of experimental renal failure on the concentrations of theophylline that cause convulsions. Adult female rats were subjected to bilateral ureteral ligation or injected with uranyl nitrate to produce renal failure or dysfunction. Sham-operated and saline-injected rats, respectively, served as controls. Theophylline was infused i.v. at either 1.03 or 2.06 mg/min until the onset of maximal seizures. Renal failure due to ureter ligation was associated with a substantial reduction of the dose of drug required to produce seizures, the concentrations of total and free (unbound) theophylline in serum and the concentrations of theophylline in the brain and cerebrospinal fluid at onset of seizures. The concentrations of theophylline metabolites were very low and did not account for the enhanced neurotoxicity. No apparent change in the neurotoxicity of theophylline was observed in rats with uranyl nitrate-induced renal dysfunction. The results of the investigation on ureter-ligated rats are consistent with recent clinical findings of a higher incidence of theophylline-induced neurotoxicity in azotemic patients. The experimental methodology may therefore be suitable for the prospective identification of other potential clinical risk factors for theophylline neurotoxicity.
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PMID:Kinetics of drug action in disease states. XVIII. Effect of experimental renal failure on the pharmacodynamics of theophylline-induced seizures in rats. 380 13

The interactions of carbamazepine with adenosine receptors were studied in two pharmacological systems. In the isolated guinea pig ileum, several adenosine agonists and carbamazepine potently inhibited nicotine-stimulated and electrically stimulated contractions in a manner sensitive to the adenosine antagonist theophylline. High concentrations of carbamazepine were able to reduce the inhibition of electrically stimulated contractions by the adenosine agonist l-methylisoguanosine. The ability of theophylline to reduce the anticonvulsant efficacy of several drugs against pentylenetetrazole-induced seizures in mice was investigated. Theophylline pretreatment failed to alter anticonvulsant protection by trimethadione and sodium valproate, but significantly decreased the anticonvulsant effects of carbamazepine and phenobarbital. These results suggest that carbamazepine may exert some of its anti-convulsant effects by acting as a partial agonist at adenosine receptors.
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PMID:Interactions of the anticonvulsant carbamazepine with adenosine receptors. 2. Pharmacological studies. 631 26

The presenting symptoms, course, and treatment of 10 patients with severe theophylline toxicity (heart rate above 120, multifocal atrial tachycardia or premature ventricular contractions, hypotension, seizures) are described. Theophylline levels at presentation averaged 66 micrograms/ml (range 30 to 180 micrograms/ml). All patients had marked tachycardia; 80 percent had gastrointestinal symptoms, 50 percent were hypotensive, and 20 percent had seizures. A known history of poor compliance or other risk factors to overdosage was present in 60 percent. Of the five patients in whom drug clearances were determined, two had uniform first-order drug elimination. Three had biphasic elimination with an initial period of delayed elimination due to either zero-order kinetics or continued drug absorption. During the first-order elimination period, mean plasma theophylline clearance was 28.0 +/- 4.3 ml per minute with a half-life of 8.2 hours. In the patients with initially delayed elimination, the mean clearance during the slow phase was 9.6 +/- 3.3 ml per minute with an apparent half-life of 31 hours. One patient was treated with charcoal hemoperfusion but the others received conservative management alone; all recovered without permanent sequelae. Propranolol and verapamil were useful in controlling supraventricular tachycardia. It appears that most patients with severe theophylline toxicity can be managed without hemoperfusion, which should be considered only when drug clearance is reduced, and hypotension, tachycardia, ventricular ectopy, or seizures are refractory to conservative measures.
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PMID:Severe theophylline toxicity. Role of conservative measures, antiarrhythmic agents, and charcoal hemoperfusion. 672 Jul 31

Theophylline-induced seizures are reported in two neonates. The serum theophylline concentration during seizures were 51.0 mg/liter and 54.0 mg/liter. Toxic symptoms prior to seizures may be absent or undetected, suporting the necessity of blood level monitoring during theophylline therapy.
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PMID:Theophylline-induced seizures in accidentally overdosed neonates. 736 May 43

We report on a 6-month-old infant with asthma who developed spasms and hypsarrhythmia on the electroencephalogram (EEG) shortly after starting oral theophylline medication. Theophylline levels at that time were just above the upper normal range. The spasms stopped and the EEG normalized when theophylline was discontinued and nitrazepam therapy started. On follow-up over the next 3 years there was no recurrence of seizures and the child's neurodevelopment has been normal. Nitrazepam was stopped at 10 months and the waking and sleeping EEG were normal at 14 months. We believe that the infantile spasms were caused by theophylline.
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PMID:Infantile spasms associated with theophylline toxicity. 775 14

This study was designed to investigate the effect of sustained-release theophylline therapy on serum pyridoxal concentration in children with bronchial asthma. Forty-two children with bronchial asthma were divided into two groups according to duration of theophylline administration: The 22 children in group A had been treated with theophylline for less than 4 weeks, whereas the 20 children in group B had been treated for more than 5 weeks. The results obtained from this study were as follows: 1) The serum pyridoxal concentration in group B was significantly lower than that those in group A (p < 0.01). 2) The serum pyridoxal concentration was not significantly correlated with the serum theophylline concentration. These findings suggest that long-term theophylline therapy can depress vitamin B6 status in children with bronchial asthma. Theophylline-induced seizure may be caused by the possible decreased in gamma-aminobutyric acid concentration in the brain as a result of decrease in gamma-aminobutyric acid concentration in the brain as a result of decrease in vitamin B6 status, even if the serum theophylline concentrations are within the therapeutic range.
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PMID:[Serum pyridoxal concentration in children during theophylline therapy for bronchial asthma]. 780 1

Seizures, often with fatal outcome, are a manifestation of pronounced theophylline toxicity. Prodromal symptoms are not always apparent, and the seizures are reported to be, in certain cases, refractory to treatment with anticonvulsant drugs. The purpose of this investigation was to examine, by an established animal model, which of the commonly used anticonvulsants can reduce the central nervous system sensitivity to theophylline neurotoxicity and what should be the preferred treatment in cases in which theophylline toxicity is anticipated. The anticonvulsant agents in doses that are found to be effective in other types of experimentally induced seizures in rats, clonazepam 5 mg/kg, diazepam 5 mg/kg, phenytoin 8 mg/kg, phenobarbital 100 mg/kg, valproic acid 150 mg/kg, and magnesium sulphate 300 mg/kg, or the vehicle (controls) were administered intravenously to Lewis female rats. Thirty minutes later, theophylline was infused at a constant rate of 1.3 mg/min until onset of maximal seizures. Theophylline concentrations in the cerebrospinal fluid, brain, and serum were assayed by a high-performance liquid chromatography method. It was found that pretreatment with either clonazepam, diazepam, phenobarbital, or valproic acid increased the central nervous system thresholds to the theophylline-induced seizures, whereas phenytoin and magnesium sulphate did not attenuate the sensitivity of the brain to the stimulatory action of this widely used bronchodilator. Therefore, whenever theophylline toxicity is suspected, treatment with either diazepam, clonazepam, phenobarbital, or valproic acid can reduce the hazard associated with theophylline-induced seizures.
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PMID:Effect of pretreatment with anticonvulsants on theophylline-induced seizures in the rat. 830 56

Theophylline has been a mainstay of asthma therapy despite its narrow therapeutic index, which makes toxicity a common problem. To study toxicity in children, we reviewed hospital laboratory records (1980 to 1988) and identified cases (n = 163) with theophylline concentrations of > 133 mumol/L (24 micrograms/ml). We reviewed these cases for symptoms of theophylline intoxication; we were interested in associating symptoms with serum drug concentrations and in understanding how intoxication occurred. The median patient age was 3.0 years; 40/163 were younger than one year. Males were 90/163 patients (55%). Patients were classified by pattern of ingestion: 20 patients had acute ingestions; 17 patients had an acute ingestion while on chronic medication; and 126 patients became toxic on chronic therapy. Symptoms were absent in 44/150 patients (29%) with theophylline concentrations of 139 to 278 mumol/L (25-50 micrograms/ml); concentrations of > 278 mumol/L (50 micrograms/ml) were always associated with symptoms. The most common clinical symptoms were tachycardia (47%) and vomiting (52%); both occurred more frequently with higher theophylline concentrations (P < 0.002 and P < 0.01). Nine patients had seizures, including five who were previously neurologically normal. Seizures developed with a theophylline concentration of < 278 mumol/L (50 micrograms/ml) in four of these five patients. There was no association between seizures and patient age or between seizures and a particular pattern of theophylline use. In 105/126 cases of intoxication associated with chronic use, the cause of the intoxication could not be determined. Appropriate management of theophylline toxicity can occur only if toxicity is recognized.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Theophylline toxicity in children: a retrospective review. 834 82

Two asthmatic children who developed status epilepticus during theophylline treatment followed by semi-coma were reported. They suffered from severe neurological sequelae. A two-year-old male received oral maintenance theophylline therapy and a four-year-old male received intravenous theophylline therapy at the time of seizures. Theophylline blood levels measured several hours after the onset of seizures were within or below the therapeutic level; 12.7 and 8.8 micrograms/ml. They had febrile convulsions prior to the onset of episode and one of them was mildly delayed in psychomotor development. Brain CT scans showed diffuse cortical low-density in the acute period. Follow up CT scans revealed progressive cortical low-density in the subacute period and subsequently reached to the peak in the 10th day and 19th day of illness respectively. We consider that the progressive and long-lasting severe cortical edema on brain CT scan is characteristic of theophylline-associated encephalopathy.
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PMID:[Two cases of theophylline-associated encephalopathy in childhood: clinical and CT findings]. 851 90


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