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)

There is no consensus on the choice of drug treatment for refractory generalized convulsive status epilepticus in children. The objective of this meta-analysis of the published literature was to determine the effects of drug treatments on efficacy (seizure cessation) and mortality in children with this condition, controlling for potential confounding factors. One hundred eleven children, treated with diazepam, midazolam, thiopental, pentobarbital, or isoflurane, met strict inclusion criteria. Diazepam was significantly less efficacious than other treatments (P = .006) stratifying for etiology. Overall mortality was 20% in symptomatic cases and 4% in idiopathic cases (P = .038). Mortality was less frequent in midazolam-treated patients (P = .021) stratifying for etiology. Midazolam appears to be a good choice for initial treatment of refractory generalized convulsive status epilepticus in children, but the attribution of differences in efficacy and mortality solely to drug effect is not possible based on the published literature.
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PMID:Efficacy and mortality in treatment of refractory generalized convulsive status epilepticus in children: a meta-analysis. 1048 6

The aim of this study was to evaluate the influence of 7-acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo(4,5 H)-2,3-benzodiazepine (LY 300164), a selective non-competitive antagonist at alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors, on the protection provided by diazepam against electrically- and chemically-evoked seizures in rodents. LY 300164 (2 mg/kg) was devoid of any significant action upon each seizure parameter in kindled rats (seizure severity, seizure duration, after-discharge duration). LY 300164 (5 mg/kg) exerted a significant anticonvulsive effect as regards seizure and after-discharge durations. Combined treatment with LY 300164 (2 mg/kg) and diazepam (0.3125-1.25 mg/kg) resulted in the clear-cut anticonvulsive activity. It is noteworthy that the antiseizure potency of the combined treatment (diazepam 1.25 mg/kg plus LY 300164 2 mg/kg) was comparable to that of diazepam (10-20 mg/kg) alone. The combination of diazepam (1.25 mg/kg) with LY 300164 (2 mg/kg) did not induce any significant motor impairment in the rotorod test or memory deficit in the passive-avoidance task. In contrast, diazepam alone (10-20 mg/kg) had pronounced adverse effects in kindled animals. LY 300164 (up to 2 mg/kg) did not influence the threshold for electro- and pentylenetetrazol-induced convulsions but potentiated the anticonvulsive action of diazepam in the maximal electroshock and pentylenetetrazol test in mice, the ED50s of the benzodiazepine being reduced from 13 to 8.7 and from 0.29 to 0.049 mg/kg, respectively. As shown in the passive-avoidance task, combination of LY 300164 (2 mg/kg) with diazepam (8.7 mg/ kg) produced significant motor and long-term memory impairment. Diazepam alone (at the dose equal to its ED50 against maximal electroshock) also caused motor and memory deficits in mice. Interaction at the pharmacokinetic level, at least in plasma, can be excluded, because LY 300164 (2 mg/kg) did not affect the free plasma diazepam concentration. In conclusion, LY 300164 potentiates the protective action of diazepam in some animal models of seizures. This profitable interaction may create a new approach for the treatment of drug resistant epilepsy or status epilepticus.
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PMID:The AMPA/kainate receptor antagonist, LY 300164, increases the anticonvulsant effects of diazepam. 1088 38

The purpose of this multicentre study of an unselected group of 178 children with prolonged convulsions or status epilepticus was to evaluate the effects of rectal administration of Diazepam by means of a rectal appliance. We found that diazepam is effective against seizures in 98% of cases, has a rapid onset of action and is safe. We recommend this form of treatment at all levels of medical care and also for use by parents or other care givers.
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PMID:[Use of rectal diazepam administration for control of epileptic seizures in children. A multicenter study]. 1091 Jun 50

Diazemuls is a very powerful anxiolytic agent with sedating and anti-epileptogenic properties. Unfortunately, until now it has not been possible to give Diazemuls accurately and safely as an infusion. A new delivery system ensures that, as an infusion, this drug is potentially very effective in treating patients with terminal agitation, status epilepticus, drug and alcohol withdrawal.
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PMID:Peripheral infusion of Diazemuls. 1096 57

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

Status epilepticus (SE) is a condition requiring emergency care. There are convulsive SE, non-convulsive SE including complex partial status and absence status, non-convulsive electric SE and pseudostatus epilepticus, although convulsive SE is the most common. Diagnosis of status epilepticus of complex partial seizures (CPS) and absence seizures was significantly delayed because delays in seeking medical attention were common. The seizures were generalized convulsive SE in 84% and CPS status in 16%, and the overall mortality rate was 15% in 41 SE patients of our study. EEG monitoring is important to make or exclude the diagnosis of SE. Diazepam is the first choice medication and effective in the management of SE, and lately, lorazepam, midazolam, propofol and pentobarbital etc as emergency therapy. Phenytoin is also considered first-line agent in the emergency management of SE. Repetitive transcranial magnetic stimulation (rTMS) led to a prolonged latency for seizure induction after an intraperitoneal injection of pentylenetetrazol (PTZ) and effectively prevented the development of status epilepticus of PTZ-induced convulsions in the rats. Our data suggest that rTMS has suppressive effects on the neuronal excitability in rats. These effects are anticonvulsive and suggest the possibility of therapeutic use of rTMS in the patients with refractory seizures.
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PMID:[Treatment of status epilepticus]. 1223 7

Intravenous access cannot always be promptly obtained when treating status epilepticus outside the hospital. We compared the efficacy and safety of diazepam rectal gel to IV lorazepam in our long-term care facility for adults with developmental disabilities. Diazepam rectal gel was given more quickly and reliably, reducing total seizure time, potential neuronal injury and other complications. A treatment protocol for treating status epilepticus with diazepam rectal gel is given.
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PMID:Treatment of out-of-hospital status epilepticus with diazepam rectal gel. 1249 50

Diazepam (DZP) is one of the most commonly prescribed drugs for treating status epilepticus (SE). A simple, sensitive and selective LC/MS/MS method with a wide linear calibration range was developed to quantify DZP and its major metabolites, N-desmethyldiazepam (DMDZP), temazepam (TZP), and oxazepam (OZP), in rat cerebrospinal fluid (CSF). The method was used to simultaneously determine the concentrations of all analytes in a small sample volume (as little as 25 microL) of rat CSF. The lower limits of quantification (LLOQ) of the method are 0.04 ng/mL for DZP and 0.1 ng/mL for its metabolites. The calibration range is 0.04-200 ng/mL for DZP and 0.1-200 ng/ml for the metabolites. All intra- and inter-assay coefficients of variation (%CV) and mean percent errors of the method are less than 12%. This method successfully addresses the need to determine low therapeutic drug concentrations in small physiological samples, namely rat CSF. Moreover, it can be used to investigate the distribution of the drug and its metabolites among blood plasma, brain tissue, and CSF in pharmacokinetic and pharmacodynamic studies in a variety of laboratory animals. With respect to animal experiments involving assays in CSF, this method addresses two of the three criteria of Russell and Bruch (Principles of Humane Experimental Techniques, 1959, Methuen and Co., London) for minimizing animal use, namely refinement and reduction.
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PMID:Simple and sensitive liquid chromatography/tandem mass spectrometry method for the determination of diazepam and its major metabolites in rat cerebrospinal fluid. 1262 12

Status Epilepticus (SE) is a medical emergency and requires prompt and aggressive treatment. Stabilization of airway, breathing and circulation and expeditious termination of seizures are immediate goals. Intravenous benzodiazepines-diazepam, midazolam or lorazepam and phenytoin are the first line drugs recommended for termination of seizures. Diazepam (or midazolam), thiopental and propofol infusion are useful for control of Refractory SE (RSE). Newer drugs are being investigated for use in SE. We prefer diazepam infusion. In children the mortality from SE ranges from 3-10% and the morbidity is twice. Mortality and morbidity are highest with SE associated with CNS infections, which is the most important cause of SE in our country. The outcome depends on the underlying etiology, age, rapidity of SE and adequacy of care. Adherence to a time-framed protocol in the emergency department helps in improving the final outcome.
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PMID:Status epilepticus: emergency management. 1278 77

We applied nonlinear analysis to the results of electroencephalography (EEG) in a pilocarpine-induced status epilepticus (SE) model to characterize nonlinear dynamics according to SE phase. Nine male Sprague-Dawley rats weighing 150-250 g were used. EEG was classified into four phases in addition to baseline EEG (phase 0) as follows: phase 1, discrete seizures; phase 2, continuous ictal discharges; phase 3, early periodic epileptiform discharges (PEDs); and phase 4, late PEDs. High-dose diazepam was administered at phase 4 to terminate SE. Diazepam controlled SE in five rats (group 1), while it failed to stop SE in the rest (group 2). The presence of nonlinearity was determined by time reversal asymmetry statistics using a surrogate data set. The correlation dimension (D(2)) was calculated to characterize the dimensional complexity of each phase of SE. EEG of later phases of SE showed strong nonlinearity, whereas no or only weak nonlinearity was noted at phases 0 and 1. D(2) showed the highest value at phase 0 and decreased progressively. Considering therapeutic responsiveness, D(2) showed significant differences between the two groups at phases 2 and 4. These results suggest that nonlinear dynamic changes in the later SE phases reflect underlying pathophysiological changes that contribute to determining therapeutic responsiveness in the pilocarpine-induced SE model.
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PMID:Nonlinear dynamic characteristics of electroencephalography in a high-dose pilocarpine-induced status epilepticus model. 1283 69


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