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

Factors which may contribute to cognitive impairments in epilepsy are briefly reviewed. In particular, memory deficits, attentional problems, psychomotor slowing and reading and writing difficulties are highlighted, and the impact of the seizures, brain damage, and anticonvulsant drugs on cognitive function noted. With regards to the latter, the impairments associated with Phenytoin and Phenobarbitone are contrasted with the minimal effects of newer anticonvulsant drugs such as Sodium Valproate and Carbamazepine.
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PMID:[Cognitive effects of antiepileptic drugs]. 311 40

Phenobarbitone at a concentration of 500 mg/l in drinking fluid of gerbils during pregnancy (60 mg/kg) and lactation (136 mg/kg) markedly reduced the proportion of animals bearing litters, decreased pup weights at birth and during later life and delayed development of the self-righting reflex, auditory startle reaction, eye opening and full fur coverage. It also prolonged the period of suckling. Scars of implantation were evident in uterine horns of 60% of treated and in none of control females that had failed to give birth. Treated offspring after weaning were given phenobarbitone (500 mg/l; 42-124 mg/kg) as their drinking fluid throughout life and a further group of gerbils received this concentration of the drug from the time of weaning. Seizure susceptibility was unaltered by the drug treatment, and the only evidence of behavioural change was seen in offspring gerbils at 6 weeks when the bout length of social investigation during encounters was increased. Drug-treated offspring showed no abnormality in brain weight relative to body weight. Weight gain and brain weight remained normal among the gerbils given phenobarbitone after weaning. The drug treatment reduced scent gland size in breeding males, though not in the offspring, and had no effect on weights of the testes or ovaries and uterus. no effect on weights of the testes or ovaries and uterus. Plasma concentrations of phenobarbitone in females of the postweaning group amounted on average to 4.4 mg/kg. Most of the adverse effects of this dose of phenobarbitone in the gerbil can thus be seen to be associated either with reproductive impairment or with exposure during sensitive periods of early development.
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PMID:Phenobarbitone: adverse effects on reproductive performance and offspring development in the Mongolian gerbil, (Meriones unguiculatus). 312 13

Electroencephalographic (EEG) studies were performed to examine the effects of several antiepileptic drugs (AEDS) on absence-like and tonic seizures in the spontaneously epileptic rat (SER: zi(zi), tm/tm,), a double mutant rat, which was obtained by mating the tremor heterozygous animals (tm/ +) with the zitter homozygous animals (zi/zi), and to determine whether the seizures in the SER correspond to human absence and tonic seizures. Spontaneous EEG was continuously recorded from the frontal cortex and hippocampus using implanted electrodes. The SER showed paroxysmal and synchronized 5-7-Hz spike-wave-like complexes in both cortical and hippocampal EEG during the absence-like state, which was characterized by immobility and staring. The animal also exhibited tonic convulsion without external stimulation concomitant with low-voltage fast waves on cortical and hippocampal EEG. In some animals, sporadic low-amplitude spikes appeared in the low-voltage fast waves during tonic convulsion. the absence-like seizures were inhibited by trimethadione (100 mg/kg intraperitoneally, i.p.) and ethosuximide 100 mg/kg i.p.), whereas the tonic convulsion was not affected by these drugs. In contrast, phenytoin (20 mg/kg i.p.) inhibited the tonic seizures without affecting the absence-like seizures. Phenobarbital (10 mg/kg i.p.) and valproate (200 mg/kg i.p.) inhibited both seizures to a similar degree. These results suggest that the SER, with both absence-like and tonic seizures, is a useful model for evaluation of AEDS.
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PMID:Effects of antiepileptic drugs on absence-like and tonic seizures in the spontaneously epileptic rat, a double mutant rat. 313 16

A continuously protective, nontoxic, oral model of chronic treatment with primidone was developed in the rat. Rats were treated with primidone (100 mg/kg) by gastric gavage twice daily for up to 8 weeks. This treatment was continuously protective as measured by seizures induced by hexafluorodiethyl ether and minimally toxic as measured by weight gain. Plasma primidone concentration reached a peak (13 micrograms/ml) 2 hours after gavage and was almost undetectable by 12 hours. Plasma phenobarbital concentration peaked (52 micrograms/ml) at 6 hours postgavage after reaching a minimum (19 micrograms/ml) at one hour postgavage. Phenobarbital concentrations measured in plasma, brain and liver after 8 weeks of chronic treatment correlated significantly between each tissue and plasma.
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PMID:Chronic primidone treatment in the rat: an animal model of primidone therapy. 318 99

Although phenobarbital is the most widely used drug to control seizures, dosage guidelines are not available for infants of varying gestational ages. The primary objective of this study was to develop age specific dosage guidelines for phenobarbital in newborn infants with seizures. Fifty-one patients (27 premature infants, gestational ages 27 to 38 weeks; 24 term infants) receiving phenobarbital, 3 to 6 mg/kg/d were studied during the first month of life. Multiple serum concentrations were determined in each patient during extended therapy. Trough serum concentration of phenobarbital ranged from 12.5 to 50.2 mcg/mL. Phenobarbital serum concentrations were within therapeutic range (15 to 40 mcg/mL) in 99 of 114 measurements at a maintenance dose of 3.5 to 4.5 mg/kg/d. The remaining 15 measurements were made in infants, greater than 35 weeks' gestation and required phenobarbital doses of 4.0 to 5.0 mg/kg/d to achieve therapeutic serum concentration. These data suggest that the initial maintenance dose of phenobarbital during the first month of life should be 3.5 to 4.5 mg/kg/d in infants less than or equal to 35 weeks and 4.0 to 5.0 mg/kg/d in those greater than 35 weeks' gestation. Term infants with asphyxia had higher trough serum concentration than those without asphyxia (P less than 0.005). In nine infants, trough serum concentration normalized for dose decreased substantially during a 3-weeks period (P less than 0.0005). This suggests that phenobarbital serum concentration should be monitored frequently during the first month of life.
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PMID:Developmental aspects of phenobarbital dosage requirements in newborn infants with seizures. 323

Primidone can be used for seizures refractory to standard antiepileptic drugs. We administered primidone, 25 mg/kg/day in 3 divided doses, to 10 patients and obtained serum levels of primidone, phenobarbital, and phenylethylmalonic acid at 1, 2, 4, 6, and 8 hours on day 1, alternate days until discharge, and after 6 weeks. Other antiepileptic drugs were discontinued in 8 of 10 patients with refractory seizures. Mean primidone levels were 10.6 +/- 4.4 micrograms/ml by day 3 and remained stable until discharge. Phenylethylmalonic acid was detected by 6 hours and increased to 11.1 +/- 4.0 micrograms/ml by day 7. Phenobarbital levels in 3 of 10 patients not previously treated with phenobarbital ranged from 0.6-3.4 micrograms/ml by day 5. The mean initial phenobarbital level was 30.1 +/- 10.5 micrograms/ml and had decreased to less than 15 micrograms/ml by day 7. Seizure control occurred within 5 days in 8 of 10 patients and was achieved by day 3 in 6 of 8 patients, coinciding with primidone levels greater than 10 micrograms/ml. No toxic effects of primidone were observed. All levels decreased during subsequent examinations suggesting auto-induction of metabolic systems. Our data indicate that seizure control is best correlated with primidone and phenylethylmalonic acid levels and unrelated to phenobarbital levels in this age group.
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PMID:Efficacy of primidone for seizure control in neonates and young infants. 324 32

Anticonvulsant activities of 3-methylphenytoin (3-MP) and 1,3-dimethylphenytoin (1,3-DMP) were observed to peak 3 hr after i.p. administration of the drugs dissolved in dimethylsulphoxide (DMSO), while maximal activity was obtained within 15 min with phenytoin. HPLC was employed to monitor the plasma concentrations of all three compounds at various time intervals after injecting 3-MP or 1,3-DMP. In both cases, phenytoin appeared in the plasma, gradually reaching 14-15 micrograms/ml in 3 hr. The time course of increase in plasma phenytoin levels correlated with that of anticonvulsant activities. It was also found that 1,3-DMP gave rise to a major unidentified metabolite as well as 3-MP and phenytoin. This unidentified metabolite eluted only half a minute in front of 3-MP in the HPLC. Mice injected with high doses of 3-MP (100 mg/kg) in DMSO exhibited severe epileptiform activities. Phenobarbital, diazepam and clonazepam were found to protect against such seizures, but not phenytoin, carbamazepine and valproic acid. This shows that 3-MP is at least a pro-convulsant, taking into account that its effects might have been enhanced by DMSO. Unlike phenytoin, 3-MP lacked the ability to inhibit synaptosomal uptakes of both glutamate and GABA. This difference may be related to the fact that phenytoin, but not 3-MP, possesses potent anticonvulsant activity.
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PMID:N-demethylation of methyl and dimethyl derivatives of phenytoin and their anticonvulsant activities in mice. 324

Phenobarbital-N-glucoside (PNG) has recently been identified as a significant metabolite of phenobarbital (PB). Five neonates treated with PB alone for seizures were studied. Serum concentration of PB ranged from 30 to 80 mg/l. Serial single daily voided specimens were analyzed for PB, PNG, and total p-hydroxyphenobarbital (PHPB). PNG was detected on the 14th day of life in 1 patient, who was the oldest by gestational age. On the 20th day of life, PNG accounted for 50% of the dose excreted in the urine. No PNG was detected in other patients by the 12th, 15th, or 16th day of life. PHPB was found on day 4, in the first urine examined, in the patient who made PNG. In other patients, PHPB was first excreted on the 4th day of life in 2 patients and on the 10th day in 2. It appears that N-glucosidation, when activated, rapidly becomes a significant route for PB metabolism in the neonate.
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PMID:Development of phenobarbital glucosidation in the human neonate. 338 23

To assess the appropriateness of hippocampal low-frequency kindling as an experimental model of epilepsy, we stimulated, bipolarly, left ventral hippocampus of 8 cats with 2 mA biphasic square wave pulses (1 msec duration) once a day. The pulse-interval was set at 300 msec. Recording electrodes were inserted in right ventral hippocampus, bilateral amygdaloid and bilateral globus pallidus. EEG was monitored before, during and after the delivery of stimulation. If the triggering of epileptic afterdischarge was observed on EEG monitoring, the delivery of stimulation was stopped immediately. Generalized convulsive seizures developed in all subjects within a mean of 26.2 days. In all seizures self-sustained epileptic afterdischarge, defined as epileptiform spikes three times the base line amplitude with a frequency greater than the stimulating pulse-interval (300 msec) in the stimulated hippocampus lead, was triggered abruptly. Therefore we could measure the number of stimulating pulses required for the triggering of epileptic afterdischarge, defined as pulse-number threshold, definitely in all cases. At the completion of kindling the pulse-number threshold was measured at 12.3 +/- 0.9 (+/- SE). After five generalized convulsions were induced we tested the stability of the pulse-number threshold and the duration of triggered epileptic afterdischarge. Both the two measures did not change statistically at the interstimulation interval from 24 hrs to 96 hrs. In addition we carried out testing with antiepileptic and antipsychotic drugs. Phenobarbital (10 mg/kg, i.p.) increased the pulse-number threshold and the after discharge duration simultaneously. Haloperidol (3 mg/kg, i.p.), oppositely, decreased the pulse number threshold and the after discharge duration.
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PMID:[Reliable induction of generalized seizures in hippocampal kindling triggered with low-frequency electrical stimulations]. 340 8

A Monozygotic twin pair had febrile seizures, only one was treated with phenobarbital from 17-30 months of age. Standard intellectual and behavioral assessments were conducted during Treatment (30 months of age), and Post-Treatment (32, 41, 48, 66 months of age). Both twins showed normal global intelligence at all assessments, however, the phenobarbital twin scored lower at all assessments. Differences in specific abilities were also seen during Post-Treatment. When phenobarbital was withdrawn, the treated twin's behavior showed immediate improvement. This experience suggests that early phenobarbital treatment may affect global intelligence through the preschool period, but that the effect is not severe. Phenobarbital also may adversely affect behavior, although the effect disappears with termination of the drug.
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PMID:Effects of phenobarbital on early intellectual and behavioral development: a concordant twin case study. 359 30


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