Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Problems with anticonvulsants in women of child-bearing potential include potential adverse effects on appearance, contraception and pregnancy. These effects must be weighed against the overwhelming benefits of anticonvulsant treatment in the majority of women with epilepsy. Coarsened features, hirsutism and acne may occur in both men and women, particularly if they are exposed to phenytoin. Valproic acid may cause weight gain and hair loss, while carbamazepine treatment carries a significant risk of skin rashes. Anticonvulsants which are liver enzyme inducers (phenytoin, phenobarbital, primidone and carbamazepine) reduce the efficacy of the oral contraceptive pill. No 'pill failure' has been reported with valproic acid. There is a risk of increased seizure frequency in pregnancy irrespective of whether anticonvulsant treatment is taken. Individual seizures carry little risk to the mother or the fetus but status epilepticus has a significant maternal and fetal mortality. The risk of status epilepticus must be taken into account when deciding whether to stop anticonvulsant treatment before pregnancy. There is a 2 to 3 times increased malformation rate in the offspring of epileptic women on treatment. This is primarily due to the drug treatment, but epilepsy itself may also increase the malformation rate. Most malformations are mild and include facial clefts, congenital heart disease and skeletal abnormalities. Valproic acid, however, carries a 1% risk of causing neural tube defects: women receiving this drug who become pregnant should have an ultrasound and alpha-fetoprotein estimation at 16 to 18 weeks of pregnancy. If any abnormality is detected then amniocentesis should be carried out. Women with epilepsy should be counselled before conception and during pregnancy. Before achieving pregnancy a women should be on optimum treatment, preferably on one anticonvulsant. Consideration should be given to withdrawal of anticonvulsant drugs in any woman who has been seizure free for 2 years or who has only mild and infrequent seizures. Folate supplementation should be started prior to conception and should continue during pregnancy. There is a tendency for anticonvulsant drug concentrations to fall during pregnancy, and the dose may need to be increased if clinically indicated. Over 90% of epileptic women who become pregnant will have uneventful pregnancies and will produce healthy infants.
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PMID:Risk-benefit assessment of anticonvulsants in women of child-bearing potential. 202 55

The usefulness of the anticonvulsant drugs is determined by the mechanisms by which the agent acts and its pharmacokinetics. The general mechanisms of action of these agents include (1) effects on neurotransmitter action, (2) effects on repetitive neuronal firing mechanisms, (3) effects on neuronal networks, and (4) effects on neuronal ionic transport. Ethosuximide, valproic acid and clonazepam are used primarily in absence epilepsy. Valproic acid is also effective against generalized tonic-clonic epilepsy. Diazepam is used primarily in status epilepticus. Valproic acid enhances gamma aminobutyric acid (GABA)-mediated inhibition, reduces repetitive firing, and reduces both inhibition and excitation in neuronal networks. Clonazepam and diazepam enhance the inhibitory action of GABA, decrease inhibition in neuronal networks and affect calcium ion transport with lesser effects on repetitive firing. Ethosuximide reduces inhibition in neuronal networks, may interact with dopamine, and possibly affects sodium and potassium ion transport. Further work is needed to assess the degree of involvement of these effects in the anticonvulsant action versus the adverse effects of these agents.
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PMID:Mechanisms of anticonvulsant drug action. II. Drugs primarily used for absence epilepsy. 310 94

A 5 years old girl with status epilepticus refractory to treatment with Diphenylhydantoin at a dose of 30 mg/kg/day and Thiopental in continuous IV perfusion at a dose of 4 mg/kg/h is presented. Control of status was achieved by continuous IV perfusion of Chlormethiazole at a dose of 10 mg/kg/h which also caused respiratory depression. Seizure activity reappeared after IV perfusion of Chlormethiazole was retired, and could be controlled only with Sodium Valproate. Mechanisms of action of Chlormethiazole and its effectiveness in treatment of refractory status epilepticus are revised.
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PMID:[Treatment of refractory status convulsivus with chlormethiazole]. 314 89

Twelve patients with benign juvenile myoclonic epilepsy (BJME) representing 4% of our population of epileptics (n = 275) are presented. Only two patients (17%) had myoclonic jerks as the only seizure type. Seven (58%) had generalized tonic-clonic seizures (GTCS) and myoclonus. Three patients (25%) had absence seizures (AS), GTCS, and myoclonic jerks. Electroencephalographic evidence of photosensitivity was found in four (33%). Auditory precipitation of seizures was found in one patient. As is the case with other primary generalized epilepsies, the onset of BJME seems to be age specific. In our series the mean age of onset in years was 4.3 for AS, 14.75 for myoclonic jerks, and 16.4 for GTCS. It took an average of 8.5 years from the onset of BJME (range, 2-20 years) and 6.5 years from the onset of GTCS (range, 2 months-6 years) until the condition was properly recognized. Five patients experienced at least one episode of myoclonic status epilepticus. Generalized, paroxysmal, symmetric polyspike and slow wave discharges are the typical EEG finding. These complexes, however, showed considerable interpatient variability. Sleep deprivation proved to be the most valuable activating procedure. Valproic acid monotherapy effectively controlled myoclonic jerks as well as associated GTCS in most patients.
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PMID:Some clinical and EEG aspects of benign juvenile myoclonic epilepsy. 642 Jan 45

The major established drugs used in the management of epilepsy are carbamazepine, valproic acid, phenytoin, phenobarbital, primidone, ethosuximide and benzodiazepine drugs. Carbamazepine and phenytoin are used mainly in the treatment of partial seizures and primarily or secondarily generalized tonic-clonic seizures. Valproic acid is effective against all types of seizures, but it is used most extensively in the management of generalized epilepsies. Ethosuximide is effective against absence seizures. Phenobarbital and primidone are effective against all types of seizures (except for absences) although they are less commonly used because of their sedative properties and adverse effects on cognition. Benzodiazepines are most valuable in the treatment of status epilepticus, but their long-term use is often associated with undesirable sedation and development of tolerance to their antiepileptic effect. Irrespective of the drug used, optimal clinical management requires individualization of dosage and dosing schedules based on careful evaluation of clinical response and sound knowledge of the pharmacokinetics and interaction potential of the individual compounds. Monitoring serum drug concentrations may provide a useful guide to dosage adjustments, particularly in the case of phenytoin, which shows dose-dependent kinetics within the therapeutic dosage range.
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PMID:Established antiepileptic drugs. 906 76

Despite progress in controlling status epilepticus (SE), a search is still in progress for a drug--a single agent--that would successfully and safely interrupt this life-threatening situation. Valproate (VPA) has been used in control of SE since the 1970s, yet only in the late 1980s was VPA first administered intravenously, with good results. Twenty adult patients in acute or static SE with generalized tonic-clonic seizures (GTCS) or simple partial motor seizures were administered VPA (Depakine Injectable 400 mg, Sanofi Winthrop) in a bolus dose of 15 mg/kg body weight and then 30 min later as a continuous infusion of 1 mg/kg/h for 24 h. The therapeutic effect was evaluated depending on the type of SE, its aetiology and the time lapse between seizure onset and drug administration. Response latency time (time between drug administration and seizure cessation) was considered as index of therapy success. SE was interrupted in < 30 min in 80% of cases (88.8% of patients with GTCS and 72.7% of those with partial simple motor seizures). A better effect was achieved in patients with static SE and in patients in whom SE lasted < 3 h before treatment. In 60% of patients with interrupted SE, the response latency time was < 20 min. The results indicate high success of VPA in SE control.
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PMID:[Intravenous valproic acid administration in status epilepticus]. 963 74

Valproate is a major broad-spectrum antiepileptic drug effective against many different types of epileptic seizures. Valproate is a first-line drug in the treatment of primary generalized seizures and syndromes, but it is also effective in other seizure and epilepsy types. The possible mechanisms of action and the pharmacokinetics of valproate are outlined. A limited number of studies on the efficacy and safety of valproate treatment in patients with West syndrome and Lennox-Gastaut syndrome have shown that even therapy-resistant people with intellectual disability can benefit from add-on valproate medication. In status epilepticus, valproate can be effective either intravenously, by gastric drip or following rectal administration. Patient tolerance towards valproate is generally good. The most serious adverse effect of valproate include hepatotoxicity and teratogenicity.
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PMID:Valproate in the treatment of epilepsy in people with intellectual disability. 1003 Apr 29

Intravenous valproate has been suggested for the treatment of status epilepticus in part because of its relatively good cardiovascular safety profile. We report a case of severe hypotension associated with intravenous valproate used to treat status epilepticus in an 11-year-old girl. Valproate 960 mg (30 mg/kg) was infused over 1 hour. The patient's blood pressure decreased from a baseline of 130/80 mm Hg to 70/55 mm Hg, 39 minutes into the infusion. Although her seizures stopped, her blood pressure fluctuated between 90/60 mm Hg and 60/30 mm Hg over the next several hours, requiring treatment with intravenous fluids and pressor therapy. Endotracheal intubation eventually was performed. Once her blood pressure stabilized, the patient improved clinically. To our knowledge, this is the first report of significant hypotension associated with intravenous valproate in the treatment of status epilepticus in the pediatric population.
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PMID:Intravenous valproate associated with significant hypotension in the treatment of status epilepticus. 1061 72

Valproic acid (VPA) is administered for a variety of indications in neurology and psychiatry. The intravenous form of VPA, valproate, has been used extensively by neurologists since the 1980s for patients with status epilepticus, as serum levels can be achieved rapidly and telemetry is not required during administration. Psychiatrists have less experience with intravenous valproate, and little is documented in the literature regarding its nonepileptic indications. Patients who are unable or unwilling to take drugs orally, or for whom rapid treatment is clinically indicated, may benefit from VPA. Neuroleptics and benzodiazepines often are given parenterally; however, they may be accompanied by side effects. Intravenous valproate was administered successfully to three patients with neuropsychiatric disorders. It is hoped that this report will increase clinicians' awareness of this important and well-tolerated treatment option.
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PMID:Intravenous valproate in neuropsychiatry. 1064 79

Valproic acid (VA) has been reported to be effective in status epilepticus (SE) when given rectally. More recently, intravenous (IV) VA has been demonstrated to be effective and safe. Pharmacokinetic studies and initial clinical experience with IV valproic acid suggest that it may have a useful role in the management of refractory status epilepticus, but the magnitude of its utility is not possible to quantify or compare with phenytoin and phenobarbital. In simple SE, IV VA provides less additional benefit, since standard therapy usually works well. IV VA may be useful as a substitute for standard simple SE therapy, but this is difficult to justify unless adverse reactions to standard therapy are anticipated. The published pediatric experience with IV VA for SE is scant.
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PMID:The role of intravenous valproic acid in status epilepticus. 1096 55


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