Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Valproic acid was added to the treatment regimens of 21 psychiatric inpatients whose response to antipsychotic medications had been inadequate, and steady-state serum valproate levels were obtained on 15. The 7 patients who had unequivocal positive therapeutic responses to valproate improved at a mean serum level of 68, with a 95 percent confidence interval of 50 to 86. The 8 nonresponders had a mean serum level of 37.5 with a 95 percent confidence interval of 13 to 62. There was a weak relationship between oral dose and serum level. Two patients never reached therapeutic levels in spite of oral daily dosages of 5 g and 6 g respectively. Therapeutic levels could not be reached by 7 patients (47%) who were taking more than 1,250 mg daily. Our results suggest that the therapeutic serum range for seizures is valid for psychiatric patients but that the usual suggested oral dosage is often inadequate. Drug interactions may account for this.
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PMID:Therapeutic levels of valproate for psychosis. 223 66

Epilepsy affects almost 1% of all pregnant women. The effect of pregnancy upon epilepsy is unpredictable for the individual patient. In one third to one half of the patients epilepsy had no effect on seizure frequency, in one fourth to one third of the patients seizure frequency increased, and in one third to one fourth it improved. Several reasons are discussed for a frequently observed tendency to a drop in plasma concentration of antiepileptic drugs during pregnancy where the daily dose was kept unchanged. For unknown reasons, perinatal lethality is up to twice as high as in controls. The risk of bearing children with malformations is approximately 1.5-3 times higher for mothers with epilepsy than in non-epileptic mothers. Apart from antiepileptic drugs the role of genetic factors, the type and severity of epilepsy and the possible influence of grand-mal seizures during pregnancy must be considered to be involved in congenital anomalies. Polypharmacy produces more frequent anomalies than monotherapy. Valproate should be avoided in the pregnant women due to the increased incidence of neural tube defects. At this time there is no reason to discourage a mother on antiepileptic drug therapy from breast feeding.
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PMID:[Epilepsy and pregnancy]. 223 39

A number of anticonvulsant drugs were studied for their efficacy in preventing seizures and death from intoxication with cocaine. Rats were first pretreated with the test drug then subjected to large doses of intraperitoneally administered cocaine. In this model, control animals developed seizures in approximately 6 min, followed by death in approximately 10 min. Statistically significant protection against seizures and death was afforded by pretreatment with diazepam, phenobarbitol and the blocker of the uptake of gamma-aminobutyric acid (GABA), SKF 100330A. Only partial protection was afforded by the N-methyl-d-aspartate (NMDA) antagonist MK 801, the benzodiazepine antagonist, flumazenil and the novel aminobenzamide, LY 201116. Valproic acid and phenytoin demonstrated limited efficacy against cocaine-induced seizures, without consistently reducing death. Carbamazepine and ethosuximide did not significantly reduce seizures or death. In this model of acute cocaine toxicity, the anticonvulsants diazepam, phenobarbital and the blocker of the uptake of GABA, SKF 100330A were the most effective in protecting rats from cocaine-induced seizures and death. These data offer insight into future approaches for the treatment of patients with the acute toxic effects of cocaine.
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PMID:Anticonvulsant modification of cocaine-induced toxicity in the rat. 232 32

Repeated paroxysmal oropharyngeal fits consisting of sialorrhea and speech arrest are described in a 5 year-4-month old patient. Investigations were initially oriented towards a laryngeal or a gastrointestinal disease. Electroencephalographic tracings showed repeated bilateral centrotemporal spikes-waves discharges which sometimes were associated with bilateral facial clonic contractions synchronous with anarthria and sialorrhea. Consciousness was preserved. Attacks were related with a cluster of fits of a partial epilepsy. Transient pseudo-bulbar palsy (anterior opercular syndrome) resulted from seizures: loss of identifiable speech, drooling with difficulties in swallowing, absence of palatal movements and of the gag reflex. Intellectual functions remained normal. Other investigations were all normal (CT scan, MRI, cytologic and immunological CSF studies). With common anticonvulsant drugs (Valproate and Carbamazepine) seizures resolved within a few weeks. These findings suggest that this particular epilepsy is an unusual type of benign partial epilepsy with centrotemporal (or Rolandic) spikes.
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PMID:[Dysphagia, speech disorders and centrotemporal spikes-waves]. 232 65

Acute effects of 4 anticonvulsants on hippocampal kindled seizures induced with about 3 Hz electrical stimulations were assessed in cats. The number of stimulating pulses required for the triggering of epileptic afterdischarge (pulse-number threshold, PNT) was used as the indicator for the seizure threshold. Duration of afterdischarge (ADD), ictal and interictal behaviors and serum drug levels were also recorded. PB produced a PNT-increase more prominently than an ADD-decrease with seizure stage regression. PHT produced only a proconvulsive effect by decreasing PNT. CBZ also produced a proconvulsive effect by decreasing PNT at a low dose, and decreased PNT and ADD simultaneously at a high dose. Conversely VPA increased PNT and ADD simultaneously. These results were discussed comparing mainly with a previous study of amygdala-generating seizures.
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PMID:Effects of anticonvulsants on hippocampus-generating seizures. 233 44

The protective activity of carbamazepine (CBZ, 60 min before testing), phenobarbital (PB, 120 min), phenytoin (PHT, 120 min), and valproate (VPA, 30 min) alone or concurrent with methylxanthine derivatives was evaluated against maximal electroshock-induced seizures (MES) in male mice. All drugs were administered intraperitoneally (i.p.), and the protection offered by antiepileptic drugs (AEDs) was expressed as ED50 in mg/kg. Caffeine sodium benzoate in doses of 0.0595-0.476 mmol/kg (11.55-92.4 mg/kg) distinctly reduced the anticonvulsant efficacy of PB, in the highest dose tested with an increase in ED50 value from 19.5 to 38 mg/kg. This methylxanthine derivative in the dose range of 0.119-0.476 mmol/kg (23.1-92.4 mg/kg) also efficiently inhibited the protective action of PHT. When combined with caffeine (0.238 and 0.476 mmol/kg), the ED50 of PHT was raised from 12 to 17 and 24 mg/kg, respectively. In doses of 0.238 and 0.476 mmol/kg, caffeine also diminished the efficacy of CBZ and VPA, and at the highest dose tested the methylxanthine elevated the respective ED50s from 13 to 20.5 mg/kg and from 270 to 420 mg/kg. Generally caffeine sodium benzoate (up to 0.476 mmol/kg) did not affect the plasma levels of studied AEDs, and only at 0.476 mmol/kg did it significantly decrease the level of PHT. Among the other methylxanthines, pentoxifylline (0.238-0.476 mmol/kg; 66.3-132.5 mg/kg) and diprophylline (0.952 mmol/kg; 242.1 mg/kg) inhibited the protective potential of PHT and the respective ED50s were raised from 12 to 16.5, 15.5, and 14 mg/kg. No significant alterations in PHT plasma levels were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of different methylxanthines on the anticonvulsant action of common antiepileptic drugs in mice. 234 49

Valproic acid and its enteric-coated derivative, divalproex sodium, have been used extensively in a wide variety of seizure disorders. Recent preliminary research demonstrates the effectiveness of valproate in the treatment of manic-depressive illness, including acute mania, prevention of bipolar episodes, and schizoaffective disorder. In uncontrolled and controlled studies, treatment-resistant patients with these disorders have responded well to valproate. Preliminary results of an ongoing community-based open trial of valproate treatment of those affective illnesses reveal that valproate is frequently effective and has a favorable side effect profile. Overall, approximately two out of three patients with refractory bipolar disorder respond to acute therapy with valproate. Response in schizoaffective patients has been moderate, and valproate seems to be less effective in the treatment of depression. Experience suggests the importance of monitoring plasma drug levels to maximize efficacy and minimize potential toxicity.
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PMID:U.S. experience with valproate in manic depressive illness: a multicenter trial. 249 53

Valproate has rapidly advanced as an antiepileptic drug in the last 15 years. This simple branched-chain fatty acid is strikingly different from previous antiepileptic drugs. Numerous clinical studies have found valproate to be highly effective in controlling generalized seizures, particularly as monotherapy. Ideally, valproate is given in three to four doses per day, because the elimination half-life varies from 6 to 15 hours, depending on concomitantly administered drugs and metabolic variations. Increasing the dosage raises the peak serum level and also increases the duration of time during which a minimum effective serum concentration is obtained. Drug interactions occur when valproate is administered with other drugs, especially other antiepileptic drugs. Side effects attributed to valproate include tremor, weight gain, hair loss, hair growth, hepatotoxicity, and neural tube defects in offspring of mothers. Monitoring serum valproate concentrations and seizure frequency are essential aspects of patient follow-up.
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PMID:The scope and use of valproate in epilepsy. 249 54

Juvenile myoclonic epilepsy (JME) is a primary generalized epilepsy that affects approximately 7% of adolescent and adult epilepsy patients. JME is characterized by myoclonic seizures alone or combined with generalized tonic-clonic seizures or absence seizures. Seizures are precipitated by sudden awakening, sleep deprivation, photic stimulation, and alcohol consumption. The ictal electroencephalogram (EEG) shows a typical 4- to 6-Hz polyspike and wave pattern; the interictal EEG may be normal. Valproate controls seizures in approximately 80% of JME patients and is recommended for successful management of this disorder.
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PMID:Juvenile myoclonic epilepsy: characteristics of a primary generalized epilepsy. 250 6

Data from 50 patients with juvenile myoclonic epilepsy (JME) were analyzed retrospectively to assess the response to drug therapy--long-term seizure control, relapse rates, and confounding factors in seizure recurrence. Valproate is the only available antiepileptic drug that has been shown to be effective in controlling the generalized seizure components of JME--myoclonic, tonic--clonic, and absence seizures--without significant side effects. Data were collected using the EpiMonitor software and represented case follow-up from 2 months to 9 years. Forty-three patients (86%) were seizure free for at least 1 year; 25 patients (50%) relapsed at some point during follow-up. Relapses were precipitated most frequently by fatigue, noncompliance, stress, sleep deprivation, and alcohol consumption. With accurate diagnosis and appropriate therapy, seizures in JME can be adequately controlled, although JME is a chronic disorder that may require lifelong therapy. To minimize relapse, patient management must also focus on patient lifestyle to eliminate or control lifestyle-associated precipitants of seizure relapse.
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PMID:Juvenile myoclonic epilepsy: long-term response to therapy. 250 7


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