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)

The First International Symposium on Alcohol and Seizures (September 1988, Washington, DC) convened experts from North America and Europe to discuss the basic and clinical research findings in this field. Most of the observations communicated at this symposium are included in this article. Emergency physicians are familiar with the alcoholic patient who presents during or after a seizure(s). This familiarity must not obscure the fact that a significant minority of these patients will have an underlying process that can cause morbidity or mortality if the unsuspecting physician does not have an organized and methodic approach to the evaluation and management of the seizing alcoholic patient. Status epilepticus should be evaluated and treated in a similar fashion, whether or not the patient is an alcoholic. Otherwise, almost without exception, there are nuances and controversies with respect to the evaluation and management of the alcoholic patient with a seizure(s), from the indications for CT scan, to the proper role of sedatives and anticonvulsants, and the need for admission. The emergency physician must remain a patient advocate. The great majority of alcoholic patients with seizures who require admission can be treated satisfactorily at the hospital of presentation.
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PMID:Seizures in the alcoholic patient. 222 89

A 15-year-old boy presented to the emergency department with status epilepticus and a blood ethanol concentration of 757 mg/dL. Mechanical ventilation and substantial amounts of benzodiazepines were required. His hospital course was complicated by aspiration pneumonia, but he had no episodes of hypoglycemia. He received 2.8 hours of hemodialysis, which increased the rate of ethanol elimination, but there is no evidence that hemodialysis improved his clinical outcome. To our knowledge, this is the highest blood ethanol level reported in a child or adolescent who survived.
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PMID:Severe ethanol intoxication in an adolescent. 760 26

1. The premorbid behaviors produced by the administration of cocaine, ethanol, their combination, as well as a metabolite produced by their co-administration, viz. cocaethylene, were defined, determined and quantified in the HS strain of mice. 2. The LD50 for ethanol was 9.71 g/kg in males and 9.45 g/kg in females, whereas the LD50 values in male and female mice for cocaine were 101.55 and 90.00 mg/kg, respectively. 3. The data indicate that clonic-tonic seizures continued into status epilepticus after cocaine administration and prior to cocaine-induced lethality. In contrast, administration of the cocaine-ethanol metabolite cocaethylene produced status epilepticus without producing clonic-tonic seizures yet still resulted in lethality. 4. Thus, both cocaine and cocaethylene may produce their lethal effects in mice through neuro-regulatory mechanisms mediating protracted seizure induction.
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PMID:Premorbid behaviors produced by cocaine, ethanol and cocaethylene in the mouse. 771 72

Sensitization and cross-sensitization to the seizurogenic effects of cocaine and cocaethylene were examined in the HS strain of mice. Animals were administered IP injections of either 48 mg/kg cocaine or 32 mg/kg cocaethylene once per day for 4 days. On the fifth day, mice were injected with either the same drug that was administered on days 1-4 or the alternative psychostimulant and the occurrence of seizure activity was recorded. Repeated cocaine administration resulted in the induction of tonic-clonic seizures and status epilepticus in 90% of the animals tested with cocaine on the fifth day. A similar increase in seizure prevalence, noted as a kindling effect, was observed in cocaethylene-treated animals tested with cocaethylene in that 90% of the mice exhibited status epilepticus on the last test day. Significant cross-sensitization was observed only in the group that received cocaethylene following repeated cocaine exposure. However, data obtained from animals injected with cocaine following cocaethylene treatment also were suggestive of cross-sensitization effects. Results are discussed in terms of the potential mechanistic differences between cocaine and its ethanol-derived product, as well as its relevance to cocaine use/abuse.
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PMID:Cocaethylene-induced kindling of seizure effects: cross-specificity with cocaine. 874 13

Fosphenytoin sodium is reviewed, and its safety is compared with that of phenytoin. After i.v. or i.m. injection, fosphenytoin, a phenytoin prodrug, is rapidly hydrolyzed to phenytoin. Free-phenytoin concentrations equivalent to those obtained with i.v. phenytoin can be achieved with fosphenytoin given at equimolar loading doses by selecting the appropriate rate of fosphenytoin administration. Fosphenytoin can be expected to interact with the same drugs that interact with phenytoin. The dosage is expressed as phenytoin sodium equivalents (PE). The standard loading dose for adults with status epilepticus is 15-20 mg PE/kg i.v. infused at 100-150 mg/min; i.m. administration is not recommended for this condition. For nonemergency situations, a 10- to 20-mg PE/kg loading dose can be given i.v. or i.m. Fosphenytoin has advantages over phenytoin injection that are related to its greater aqueous solubility, which obviates the extreme alkalinity, propylene glycol, and ethanol needed in the injectable phenytoin formulation. Intravenous fosphenytoin has been associated with less soft-tissue injury and fewer adverse effects in general than phenytoin. Fosphenytoin, when administered i.m., is completely absorbed, is relatively well tolerated, and provides more predictable serum drug concentrations than i.m. phenytoin. Fosphenytoin offers practical and clinical advantages over i.v. phenytoin.
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PMID:Safety of fosphenytoin sodium. 904 73

The alcohol withdrawal syndrome occurs in the hours or days after the cessation of alcohol drinking in an alcohol dependent patient. The alcohol withdrawal syndrome is produced by the emergence of the biological mechanism of neurological tolerance to ethanol. The clinical manifestations of the alcohol withdrawal syndrome are due to the hyperexcitability of the central nervous system: agitation, excitability, tremor, convulsions, status epilepticus, delirium, sympathetic hyperactivity. Usually benign, the alcohol withdrawal syndrome is frequently manageable on an ambulatory basis, as long as no clinical counter-indication is present such as a serious previous alcohol withdrawal syndrome, previous withdrawal convulsions, a significant medical or psychiatric comorbidity, a high level of alcohol consumption, a pregnancy, or the lack of an effective familial or social support. The ambulatory management of the alcohol withdrawal syndrome requires frequently the use of a sedative drug. Benzodiazepines used orally for a duration of 3 to 5 days are actually considered a first choice. Inability to work and drive is frequently present for several days.
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PMID:[Ambulatory management of alcohol withdrawal syndrome]. 1057 35

The misuse of benzodiazepines (BNZ)s may result in serious side effects. Three cases of convulsive status epilepticus (CSE) following abrupt discontinuation of long-term use of 25 mg of lorazepam in one patient and more than 20 mg of flunitrazepam in two patients are presented; they were non-epileptics and free of other high-risk factors for seizures. A favorable outcome for all three cases was noted. They remain free of seizures without antiepileptic treatment. Nevertheless, because of the extensive use of benzodiazepines, such rare high-risk side effects must be emphasized.
Drug Alcohol Depend 2000 Apr 01
PMID:Convulsive status epilepticus following abrupt high-dose benzodiazepine discontinuation. 1070 79

Intranasal (IN) administration is a promising approach for rapid-onset delivery of medications. In order to assess the feasibility of this approach for the emergency treatment of status epilepticus, three anticovulsants, i.e. diazepam (DZ), clonazepam (CZ), and a monocarbamate-based new compound (MCA) were studied in rabbits for the pharmacokinetics (PK) and pharmacodynamic (PD) response following intravenous (IV) and IN administrations. The animals were intranasally dosed with DZ (1 mg/kg), CZ (0.2 mg/kg), and MCA (5 mg/kg), dissolved in 200 microl of vehicle consisting of propylene glycol (PG), ethanol (EtOH), and water in the presence or absence of 1% sodium glycocholate (SGC) using single and repeated dosing schedules. Both DZ and CZ were absorbed very rapidly from 1% SGC/60% PG-30% EtOH-10% Water after IN single application; the T(max)'s were less than 2 min. The absorption rate of MCA was relatively slower with the peak time of 13-32 min. The bioavailability of single IN administration for DZ, CZ, and MCA determined over the first 2 or 4 h was found to be 77, 45, and 79%, respectively. The peak plasma level of DZ increased linearly with increasing the volume fraction of EtOH in the ternary cosolvent (20% to 60%). A repeated IN application of DZ, 5 min after the first dose, doubled the C(max) and AUC(0-2 h) values of the first one, whereas those of CZ and MCA resulted in an increase of 73-94% of the first dose. A single IN application of DZ- and CZ-containing formulations produced a PD response within 1.5 min, which was comparable to that of an IV injection. These results suggest that single or repeated IN applications of DZ, CZ, and MCA in a hydroalcohol-glycolic formulation might represent a viable approach to achieving a rapid systemic absorption of these anticonvulsants during the emergency treatment of status epilepticus and other types of seizures.
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PMID:Rapid-onset intranasal delivery of anticonvulsants: pharmacokinetic and pharmacodynamic evaluation in rabbits. 1079 28

An ethyl laurate-based microemulsion system with Tween 80 as surfactant, propylene glycol and ethanol as cosolvents was developed for intranasal delivery of diazepam. Phase behavior and solubilization capacity of the microemulsion system were characterized and in vivo nasal absorption of diazepam from microemulsion formulations was investigated in rabbits. A single isotropic region, which is considered as a bicontinuous microemulsion, was found in the pseudo-ternary phase diagrams developed at various Tween 80: propylene glycol: ethanol ratios. With the increase of Tween 80 concentration, the microemulsion region area, microemulsion viscosity, and the amount of H(2)O and ethyl laurate solubilized into the microemulsion system increased; however, the increase of ethanol percentage produced opposite effects. Diazepam, a practically water-insoluble drug, displayed a high solubility of 41 mg/ml in a microemulsion consisting of 15% ethyl laurate, 15% H(2)O, and 70% (w/w) surfactant/cosurfactant (Tween 80:propylene glycol:ethanol at 1:1:1 weight ratio). Nasal absorption of diazepam from this microemulsion was found to be fairly rapid. At 2 mg/kg dose, the maximum drug plasma concentration was arrived within 2-3 min, and the bioavailability (0-2 h) after nasal spray compared with intravenous injection was about 50%. These results suggest that this ethyl laurate-based microemulsion may be a useful approach for the rapid-onset delivery of diazepam during the emergency treatment of status epilepticus.
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PMID:Development of an ethyl laurate-based microemulsion for rapid-onset intranasal delivery of diazepam. 1195 6

The relationship between alcohol and seizures is complex and multifaceted. The prevalence of epilepsy in alcohol-dependent patients of western industrialised countries may be at least triple that in the general population, whereas the prevalence of alcoholism is only slightly higher in patients with epilepsy than in the general population. The seizure threshold is raised by alcohol drinking and declines on cessation of drinking. As a result, during withdrawal from alcohol, usually 6-48 hours after the cessation of drinking, seizures may occur. Alcohol acts on the brain through several mechanisms that influence seizure threshold. These include effects on calcium and chloride flux through the ion-gated glutamate NMDA and GABA receptors. During prolonged intoxication, the CNS adapts to the effects of alcohol, resulting in tolerance; however, these adaptive effects seem to be transient, disappearing after alcohol intake is stopped. Although the relationship of seizures to alcohol use is likely to be dose dependent and causal, the available clinical data do not suggest that alcohol use results in seizure genesis. However, a genetic predisposition to alcohol withdrawal seizures is possible. Other seizures in alcohol-dependent individuals may be due to concurrent metabolic, toxic, infectious, traumatic, neoplastic and cerebrovascular diseases and are frequently partial-onset seizures. Alcohol abuse is a major precipitant of status epilepticus (9-25% of cases), which may even be the first-ever seizure type. Prompt treatment of alcohol withdrawal seizures is recommended to prevent status epilepticus. During the detoxification process, primary and secondary preventative measures can be taken. A meta-analysis of controlled trials for the primary prevention of alcohol withdrawal seizures demonstrated a highly significant risk reduction for seizures with benzodiazepines and antiepileptic drugs and an increased risk with antipsychotics. A meta-analysis of randomised, placebo-controlled trials for the secondary prevention of seizures after alcohol withdrawal showed lorazepam to be effective, whereas phenytoin was ineffective. Because withdrawal seizures do not recur if the patient remains abstinent, long-term administration of antiepileptic drugs is unnecessary in abstinent patients. The first seizure not related to alcohol withdrawal should not result in permanent drug treatment in an alcohol-dependent patient, because of poor compliance and the high likelihood of remission. The treatment of alcohol dependence is more important and should be prioritised before the prevention of further seizures.
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PMID:Seizures in alcohol-dependent patients: epidemiology, pathophysiology and management. 1459 42


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