Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014547 (focal epilepsy)
 1,627 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gray and white matter were obtained during neurosurgical therapy of focal epilepsy from 17 patients. In 10 patients, receiving only phenobarbital, the drug was uniformly distributed between gray and white matter. Phenytoin concentrations averaged 1.4-fold greater in white matter than in gray matter when expressed per gram wet weight of tissue. The gray matter/plasma ratio of phenytoin was approximately 2-fold greater than that of phenobarbital. Carbamazepine levels were also slightly greater in white matter. The data revealed wide differences between drugs in the relative concentrations in gray and white matter, which must be taken into account in any quantitative studies of anticonvulsant drug levels in the brain.
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PMID:Distribution of anticonvulsant drugs in gray and white matter of human brain. 40 8

The effects of delta 9-tetrahydrocannabinol (delta 9-THC), two of its metabolites, 8 beta-hydroxy-delta 9-THC and 11-hydroxy-delta 9-THC, and cannabidiol were comparatively studied by means of an iron-induced cortical focal epilepsy in conscious rats with chronically implanted electrodes. delta 9-Tetrahydrocannabinol produced depression of the spontaneously firing epileptic focus, excitatory behavior, generalized after-discharge-like bursts of epileptiform polyspikes and frank convulsions. The pharmacological profiles of the two metabolites differed from that of the parent compound: 11-Hydroxy-delta 9-THC did not precipitate convulsions, but it did elicit all the other effects of delta 9-THC; the 8 beta-hydroxy derivative, on the other hand, exerted only two delta 9-THC-like effects; that is, it evoked polyspike bursts and convulsions. In contrast, cannabidiol, even in large doses (100 mg/kg) was devoid of all the effects of delta 9-THC. Furthermore, pretreatment with cannabidiol markedly altered the responses to delta 9-THC in the following ways: focal depression was partially blocked, polyspike activity was enhanced and convulsions abolished. Phenytoin pretreatment elicited similar effects, but it failed to block the delta 9-THC-induced convulsions. In general, the cannabinoids exhibit a wide spectrum of CNS effects ranging from focal depression to convulsions; specifically, however, the pharmacological profile of each agent can differ markedly; for example, the convulsant properties of delta 9-THC are not a universal characteristic of this class of drugs.
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PMID:Central excitatory properties of delta 9-tetrahydrocannabinol and its metabolites in iron-induced epileptic rats. 627 53

Current trends and controversies in the antiepileptic drug therapy are reviewed from a clinical view. The usefulness of prophylactic therapy of febrile seizures and posttraumatic seizures or posttraumatic epilepsy is compromised by difficulties in the management of the patients especially by noncompliance. Previously untreated epilepsies can be treated successfully in 70--80% of the patients. Phenytoin or carbamazepine are equally effective for generalized tonic-clonic seizures of focal seizures, while absence seizures are controlled by ethosuximide or valproic acid. Only when the epilepsy is uncontrolled despite high plasma concentrations which cannot be raised because of side effects, a second drug should be given. A second drug is successful in about one out of six patients with focal epilepsy. Phenytoin, carbamazepine, phenobarbital and primidone seem to be equally effective for these drug-resistant cases. Status epilepticus can be treated with intravenous diazepam or phenytoin and, if necessary, with an infusion of phenytoin. Rectal diazepam is useful for acute pediatric therapy. Drugs of second choice are clonazepam, phenobarbital, lidocaine, and clomethiazole. In the pregnant epileptic patient a drop in the plasma concentration of antiepileptic drugs mainly through non-compliance and seizure provocation through sleep deprivation are major sources for the deterioration of epilepsies during pregnancy. The "fetal antiepileptic drug syndrome", malformations and an increased risk for epilepsy in the child are discussed as an interaction of parental epilepsy and drug-exposure during pregnancy. Finally, the interpretation of abnormal clinical chemistry data is reviewed. Disorders of the liver, bone, thyroid gland and blood are rarely seen in treated epileptic patients usually when specific risk factors are present. The over-interpretation of laboratory abnormalities e.g. an isolated increase of gamma-GT may lead to iatrogenic deterioration of epilepsy when the effective dose of the drug is reduced for unfounded fear of hepatic toxicity.
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PMID:[Pharmacotherapy of epilepsy--current problems and controversies]. 641 28

Somatosensoric evoked potentials produced during a stimulation of median nerve have been recorded in 64 patients with untreated seizures, including 9 patients with partial seizures, 27 patients with partial complex seizures, partial secondary generalized seizures (22 patients), and 6 patients with primary generalized seizures. Higher mean amplitude of N13 wave has been noted in patients with simple partial seizures and complex seizures whereas a mean amplitude of wave N20 has been higher in case of partial primary generalized seizures. Measurements have been repeated in 45 patients with focal epilepsy within approximately 3 months. These patients have been given either phenytoin (22 individuals) or carbamazepine (21 individuals). Phenytoin prolonged mean proximal conduction time (N9-N13) while carbamazepine prolonged mean central conduction time (N13-N20). Both therapies prolonged mean peripheral conduction time in both groups but only in the group treated with carbamazepine observed changes were statistically significant.
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PMID:[Effect of monotherapy with phenytoin or carbamazepine on somatosensory evoked potentials in patients with newly diagnosed epilepsy]. 802 47

We report the case of a 39-year-old woman with onset of daily epigastric sensations associated with brief episodes of unresponsive blank stare, which have been interpreted as complex partial seizures with occasional secondary generalisation. Phenytoin as monotherapy and in combination with valproate had not been effective. During video-EEG we recorded typical absences with brief 3 second spike, and slow-wave discharges of up to 5 seconds, which were recognized by the patient herself. All absences were preceded by epigastric sensations. There was no indication of focal epilepsy. Monotherapy with valproate substantially decreased the frequency of the absences. In conclusion, this case is peculiar for several reasons: 1) late onset of absence epilepsy, 2) epigastric sensation at onset of absence seizures, 3) recognition of brief "phantom" absences and 4) presumable adverse effects of phenytoin.
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PMID:Epigastric sensations as an unusual manifestation of adult absence epilepsy. 1131 17

Phenytoin (PHT) is an antiepileptic drug widely used in the treatment of focal epilepsy and status epilepticus, and effective in controlling focal seizures with and without tonic-clonic generalization and status epilepticus. The metabolization of PHT is carried out by two oxidative cytochrome P450 enzymes CYP2C9 and CYP2C19; 90% of this metabolization is done by CYP2C9 and the remaining 10% by CYP2C19. Genetic polymorphism of CYP2C9 may reduce the metabolism of PHT by 25-50% in patients with variants *2 and *3 compared to those with wild-type variant *1. The frequency distribution of CYP2C9 polymorphism alleles in patients with epilepsy around the world ranges from 4.5 to 13.6%, being less frequent in African-Americans and Asians. PHT has a narrow therapeutic range and a nonlinear pharmacokinetic profile; hence, its poor metabolization has significant clinical implications as it causes more frequent and more serious adverse effects requiring discontinuation of treatment, even if it had been effective. There is evidence that polymorphisms of CYP2C9 and the use of PHT are associated with an increase in the frequency of some side effects, such as cerebellar atrophy, gingival hypertrophy or acute cutaneous reactions. The presence of HLA-B*15:02 and CYP2C9 *2 or *3 in the same patient increases the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis; hence, PHT should not be prescribed in these patients. In patients with CYP2C9 *1/*2 or *1/*3 alleles (intermediate metabolizers), the usual PHT maintenance dose (5-10 mg/kg/day) must be reduced by 25%, and in those with CYP2C9 *2/*2, *2/*3 or *3/*3 alleles (poor metabolizers), the dose must be reduced by 50%. It is controversial whether CYP2C9 genotyping should be done before starting PHT treatment. In this paper, we aim to review the influence of CYP2C9 polymorphism on the metabolization of PHT and the clinical implications of poor metabolization in the treatment of epilepsies.
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PMID:CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment. 2963 28