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

A series of 47 children with absence seizures was analysed retrospectively. Fourteen of these children also had other types of seizures, and four had repeated episodes of absence status. The age at onset of absence seizures ranged from 1 1/2 to 13 years (mean, 7.9 years). The mean follow-up was 5.5 years. Ethosuximide (ESM) was used as the drug of first choice in 43 children, and valproate (VPA) was used first in 4 children; 15 of the patients later received VPA alone or in combination with ESM. A 100% reduction in seizure frequency was achieved in 38 children (80.8%). Of these, 23 has received ESM (21 ESM; 2 ESM + nitrazepam) and 15 had received VPA (6 VPA; 9 VPA + ESM). Of the latter group, 11 children had had an unsuccessful trial of ESM. VPA was superior in the treatment of children who had EEG polyspikes or absence status. A seizure reduction of 50% to 75% was achieved in 7 children (14.9%). Two patients (4.3%) had refractory seizures. A transient Stevens-Johnson syndrome occurred in a patient treated with ESM. Other side effects were mild and transient. Both ESM and VPA are needed in the treatment of absence seizures. In refractory cases, the combination of these drugs appears to be beneficial.
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PMID:Absence seizures: valproate or ethosuximide? 642 96

The ontogeny of petit mal-like seizures induced by gamma-hydroxybutyrate (GHB) was investigated. The prodrug of GHB, gamma-butyrolactone (GBL) was administered in varying dosages under continuous EEG monitoring from cortical and depth electrodes to rats varying in postnatal age from 1 to 85 days. The brain pharmacokinetics of GHB were determined at various ages as was the effect of ethosuximide on GBL-induced EEG changes. In adult rats, GBL produced a predictable sequence of electrical events beginning with spike bursts and progressing to polyspiking separated by low voltage activity. In 1-day-old rats, GBL produced voltage suppression with stupor. Poorly organized spiking appeared at postnatal day 3 and by day 9 marked burst suppression with polyspiking separated by low voltage activity was noted. However, the full array of electrical events seen in adult rats did not appear until day 28. Ethosuximide was ineffective against GHB seizure until the third postnatal week of life. GHB had a longer half-life in brain in the first week of postnatal life. These data suggest that in the rodent, petit mal-like seizure activity may require a fully mature brain and raise the possibility of different mechanisms being responsible for the various stages of EEG changes induced by GBL.
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PMID:Ontogeny of gamma-hydroxybutyric acid. II. Electroencephalographic effects. 643 19

The high seizure susceptibility in epileptic fowl is an autosomal recessive trait characterized in homozygotes by seizures that occur spontaneously and in response to photic stimulation or hyperthermia. Both of the latter stimuli can be used to evoke seizures in drug studies. Epileptic fowl have abnormal inter-ictal EEG activity. When exposed to photic stimulation spiking is apparent on the EEG at seizure onset. Phenobarbital, primidone, phenytoin, and valproic acid reduce seizure susceptibility at plasma concentrations approximating those used to control generalized and focal cortical tonic-clonic seizures in humans. Carbamazepine and the benzodiazepines also reduce seizure susceptibility. These data indicate that epileptic fowl provide a useful model for generalized and focal cortical tonic-clonic epilepsies. Ethosuximide was inactive in epileptic fowl. However, trimethadione had anticonvulsant activity indicating that this model is only relatively specific for the above seizure types. When seizures were evoked by hyperthermia phenobarbital but not phenytoin or valproate reduced seizure susceptibility. GABA (gamma-aminobutyric acid), AOAA (amino-oxyacetic acid) and THPO (4,5,6,7-tetrahydroisoxazolo[4,5-c] pyridin-3-ole, a glial specific inhibitor of GABA uptake) all have anticonvulsant activity against seizures evoked by photic stimulation in young chicks. These data indicate that this model may be particularly useful for studies of the anticonvulsant activity of compounds designed to enhance GABAergic transmission.
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PMID:Anticonvulsants in epileptic fowl. 654 9

Effects of metrazol (pentylenetetrazole and ethosuximide were studied in male albino rats aged 7, 12, 18 and 90 days. The 18-day-old rats exhibited the highest sensitivity to metrazol. CD50s in the remaining three age groups were nearly the same. Ethosuximide was reliably effective against metrazol only in adult rats; in young animals it did not significantly change CD50s. Metrazol induced in ethosuximide-pretreated young rats either modified (long-lasting minimal seizures in 18-day-old animals) or new seizure patterns (minimal seizures in 7- and 12-day-old rats).
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PMID:Influence of ethosuximide on metrazol-induced seizures during ontogenesis in rats. 666 17

The addition of valproic acid to ethosuximide in treatment to prevent seizures caused increased serum concentration of ethosuximide in four of five patients observed. Ethosuximide levels increased from 73 to 112 microgram/ml (53% higher), with concomitant toxicity. Both were reversed by reduction of the ethosuximide dose from 27.4 to 20.4 mg/kg. Serum concentrations of these two drugs should be monitored closely when they are given together.
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PMID:Valproic acid and ethosuximide interaction. 677 74

We evaluated the effects of phenytoin, carbamazepine, phenobarbital, sodium valproate, and ethosuximide on penicillin-induced spike foci. Phenytoin, carbamazepine, and phenobarbital at blood levels within or slightly above the human therapeutic range in humans increased spike frequency, decreased spike duration, and abolished after discharges. Ethosuximide and sodium valproate had no statistically significant effect even at blood levels considered toxic in humans. The experimental spike focus and the method of analysis appear useful for: (1) detection of new potentially anticonvulsant drugs, (2) classifying new potentially anticonvulsant drugs according to the type of clinical seizure for which benefit is most likely, and (3) comparing different anticonvulsant drugs.
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PMID:Quantitative evaluation of anticonvulsant effects on penicillin-induced spike foci in cats. 679 Oct 52

Ethosuximide kinetics were determined in six normal healthy adults after a single dose (phase 1) and at steady-state (phase 2). After the completion of phase 2, valproic acid was added to the ethosuximide regimen (phase 3) to assess the possibility of drug interaction. Between phases 1 and 2 total clearance fell from 13.1 to 11.1 ml/hr/kg (P less than 0.05) and nonrenal clearance fell from 10.1 to 8.3 ml/hr/kg (P less than 0.05). When valproic acid was added (phase 3) there was no further change in total or nonrenal clearance (11.2 and 8.3 ml/hr/kg). To assess the possibility of nonlinear ethosuximide kinetics a review was conducted of patients who received ethosuximide as sole therapy for absence seizures. Of 106 patients, 10 met the required criterion that defined steady state. Data from seven of the 10 patients showed evidence of a nonlinear relationship when steady-state ethosuximide concentrations were plotted against dose.
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PMID:Ethosuximide kinetics: possible interaction with valproic acid. 680 51

The convulsive actions of aminophylline (APH) and imidazole (IDZ) have been tested against a series of anticonvulsants, and their patterns of sensitivity to these agents are compared with those of other convulsants. APH was antagonized by phenobarbital and chloridiazepoxide, but less effectively than is pentylenetetrazol. Antagonism by trimethadione was not significant. Ethosuximide, phenytoin and aminooxyacetic acid potentiated APH, an effect not seen with other convulsants in our previous studies. IDZ-induced seizures were found to be relative refractory to anticonvulsants, but were antagonized to a small degree by all of those mentioned above except phenytoin; aminooxyacetic acid was relatively the most effective. Phenytoin potentiated IDZ-induced seizures. Subconvulsive doses of APH potentiated pentylenetetrazol- and 3-mercaptopropionic acid-induced seizures about equally, as did IDZ. Possible mechanism of action are discussed.
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PMID:Aminophylline and imidazole as convulsants. 721 70

Carbamazepine and ethosuximide are used together to treat epileptic mixed-seizure patterns. Since carbamazepine has been shown to induce drug-metabolizing enzyme(s) in the liver, it follows that carbamazepine may alter ethosuximide disposition. Six normal subjects took one 250-mg ethosuximide capsule twice each day for 55 consecutive doses (study days 1 to 28) and one 200-mg carbamazepine tablet each evening from study days 11 to 27. Plasma samples were collected on study days 10, 17, 21, and 28. Mean steady-state concentrations of ethosuximide declined by 17% from a preinduction (study day 10) level of 32.2 +/- 5.6 micrograms/ml to a postinduction level of 26.8 +/- 5.2 micrograms/ml on study day 28. Ethosuximide clearance increased (alpha = 0.05) between study days 10 and 28 from 0.664 +/- 0.120 to 0.800 +/- 0.0154 l/hr. The time course of induction was analyzed using a kinetic induction theory. Ethosuximide half-life was lowered from mean - 53.7 +/- 11.5 hr (before induction) to mean = 44.6 +/- 10.7 hr (after induction); the difference between some subjects was large. These data show that ethosuximide disposition is altered by carbamazepine.
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PMID:Kinetics of a carbamazepine-ethosuximide interaction. 743 84

The potency of eight standard anticonvulsants was tested in dose-response studies on kindled rats. Animals with either amygdala- or cortical-generalized seizures were used, and the effects of drugs were assessed on: (1) amygdala focal activity; (2) cortical focal activity; and (3) the generalized convulsion triggered from either focus. Ethosuximide, which is used against absence attacks, was not effective at subtoxic levels against any type of kindled seizure. The seven other drugs, all of which are effective against tonic-clonic seizures, were found to be: (a) most potent against generalized convulsive seizures; (b) slightly less potent against cortical focal activity; and (c) only partially effective against amygdala focal activity even at high (toxic) doses. The effect of these drugs on kindled seizures closely parallels their known clinical effects against (respectively) tonic-clonic, simple partial, and complex partial attacks. It is concluded that the kindling preparation could provide new pharmacological models for several different types of clinical seizure. Its most important use, however, is likely to be as a model for complex partial seizures, since there is at present no satisfactory pharmacological model for these common and drug-resistant attacks.
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PMID:Development of a new pharmacological seizure model: effects of anticonvulsants on cortical- and amygdala-kindled seizures in the rat. 743 34


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