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 effects of clinically used anticonvulsant drugs on high-frequency sustained repetitive firing (SRF) of action potentials and on postsynaptic responses to iontophoretically applied gamma-aminobutyric acid (GABA) have been compared to establish a classification of anticonvulsant drugs based on cellular mechanisms of action. By using concentrations in the range of therapeutic cerebrospinal fluid values in humans, drugs have been separated into three categories: Phenytoin, carbamazepine, and valproic acid limited SRF, but did not alter GABA responses. Phenobarbital, clonazepam, and diazepam augmented GABA responses and limited SRF only at concentrations above the therapeutic range in ambulatory patients but that are achieved in the acute treatment of status epilepticus. Ethosuximide failed to affect SRF or GABA responses even at supratherapeutic concentrations. Ability of an anticonvulsant to limit SRF correlated well with efficacy against generalized tonic-clonic seizures clinically and against maximal electroshock seizures in experimental animals. Augmentation of GABA responses and lack of limitation of SRF correlated with efficacy against generalized absence seizures in humans and against pentylenetetrazol-induced seizures in animals. However, ethosuximide must act against generalized absence seizures and against pentylenetetrazol-induced seizures by a third, as yet unknown, mechanism. Other actions occurring at supratherapeutic concentrations correlated with clinical toxicity.
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PMID:Anticonvulsant drug mechanisms of action. 240 25

Alterations of consciousness with impaired perception and drive persisting over hours to days can be due to a nonconvulsive status epilepticus. This possibility has to be considered not only in patients with already known epilepsy, but also in those with a negative history for seizure disorders. The immediately recorded electroencephalogram (EEG) provides decisive clues. In the case of petit mal status most frequently appear tiredness, reduced vigilance and lack of drive. The EEG shows a generalized spike-wave activity. In status psychomotoricus, the clinical symptomatology varies from case to case. It can be characterized by anxiety, dreamy states or productive-psychotic states with agitation, automatisms and hallucinations. In the EEG a temporal or temporally-accentuated epileptic activity will be recorded. Transitional and mixed forms of petit mal status and status psychomotoricus can also be found. I.v. injections of benzodiazepines (clonazepam, diazepam) are an appropriate therapy for any type of nonconvulsive status epilepticus. Phenytoin is indicated in status psychomotoricus, but contra-indicated in the case of petit mal status.
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PMID:[Epileptic impaired consciousness in adults]. 250 9

During status epilepticus, rapid IV access for the administration of anticonvulsant drugs can be a very difficult and time-consuming procedure. Our study evaluated whether therapeutic serum levels of phenobarbital and phenytoin could be obtained by the intraosseous route. Twenty domestic swine weighing 10 to 20 kg were divided into two groups (ten each). In one group, phenobarbital 20 mg/kg was administered either intravenously (five) or intraosseously (five). The second group received phenytoin 15 mg/kg either intravenously (five) or intraosseously (five). All animals had samples for anticonvulsant levels drawn from an indwelling arterial cannula at one, three, five, seven, ten, 15, and 30 minutes after dosing. Anticonvulsant levels were found to be statistically significantly higher with IV administration (P less than .01). However, phenobarbital levels were therapeutic by the intraosseous route, while phenytoin levels were below the therapeutic range after the ten-minute interval. Bone marrow levels 45 minutes after infusion were 13.5 micrograms/mL (phenobarbital) and 11.5 micrograms/mL (phenytoin). Our study demonstrates that current IV dosing of phenobarbital 20 mg/kg given intraosseously obtains and maintains therapeutic serum levels. Phenytoin 15 mg/kg does not maintain therapeutic levels and cannot be recommended for intraosseous administration.
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PMID:Comparison of intraosseous and intravenous routes of anticonvulsant administration in a porcine model. 275 81

The results of therapy have been analyzed in a series of 192 patients admitted for status epilepticus over 7 years in two intensive care units. Most (142 cases without any prior epilepsy) corresponded to secondary forms. In 2/3 of the cases, the patients were admitted because of failure of benzodiazepines and/or phenobarbitone. Sodium thiopentone achieved control of seizures in 75%; short-acting barbiturates should be especially prescribed in grand mal status with impending brain anoxia. Diphenylhydantoin would appear suitable in non-life-threatening conditions such as serial seizures or partial status. Chlormethiazole often succeeds in controlling convulsive status which has proved refractory to other treatment. Supportive management is mandatory: 52% of patients required respiratory assistance. Fatalities (36%) exclusively correspond to the underlying cerebral conditions and systemic disorders.
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PMID:[Treatment of status epilepticus in the adult. Retrospective analysis of 192 cases treated in intensive care units]. 286 66

The actions of clinically used anticonvulsant drugs on sustained high frequency repetitive firing of action potentials and on responses to gamma aminobutyric acid (GABA) have been determined using mouse neurons in cell culture, and a classification of anticonvulsant drug actions has been developed based on these cellular actions. Actions of the anticonvulsant drugs were accepted as clinically relevant only if they occurred at concentrations achieved in cerebrospinal fluid or in plasma unbound to plasma proteins. Based on their cellular mechanisms of actions, drugs have been divided into 3 categories: (1) Phenytoin, carbamazepine and valproic acid limited sustained high frequency repetitive firing but did not alter GABA responses. (2) Phenobarbital and the benzodiazepines, clonazepam, diazepam and nitrazepam, augmented postsynaptic GABA responses. These drugs limited sustained high frequency repetitive firing only at concentrations above the therapeutic range in ambulatory patients, but equal to concentrations achieved in the acute treatment of status epilepticus. (3) Ethosuximide failed to reduce sustained high frequency repetitive firing or enhance GABA responses even at supertherapeutic concentrations. Limitation of sustained high frequency repetitive firing by anticonvulsant drugs correlated well with efficacy against generalized tonic-clonic seizures in man and against maximal electroshock seizures in experimental animals. Enhancement of postsynaptic GABA responses correlated with efficacy against generalized absence seizures in man and against pentylenetetrazol seizures in animals. Ethosuximide, however, did not alter GABA responses or sustained high frequency repetitive firing suggesting that its action against generalized absence seizures in man and pentylenetetrazol seizures in experimental animals occurs by an additional, as yet unknown, mechanism.
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PMID:Mechanisms of anticonvulsant drug action. 288 43

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

Secondarily generalized convulsive status epilepticus was induced by intraperitoneal (i.p.) injection of D,L-homocysteine thiolactone to rats with actively epileptogenic cobalt lesions in motor cortex. This induced focal motor seizures which secondarily generalized. Control animals not treated with antiepileptic drugs had a mean of 18.3 generalized convulsions over a mean period of 103.8 min. Electrographic patterns seen during status epilepticus are described and are very similar to those seen during human status epilepticus. Phenytoin, phenobarbital, diazepam and lorazepam were all effective in arresting the generalized seizures when given i.p. after the second such seizure. Efficacy was serum drug concentration dependent. Concentrations effective in arrest of generalized seizures in this model are similar to those reported to be effective in the treatment of human status epilepticus. Diazepam ED50s for control of generalized tonic-clonic seizures and for arrest of all seizure activity were determined.
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PMID:Experimental secondarily generalized convulsive status epilepticus induced by D,L-homocysteine thiolactone. 319 90

In a randomized, nonblinded clinical trial, 36 consecutive patients with generalized convulsive status epilepticus were treated with either combination diazepam and phenytoin (DZ/DPH) or phenobarbital (PB). Phenytoin was added to the PB regimen if seizures persisted for 10 minutes after beginning therapy. The cumulative convulsion time (total time spent in active convulsive movements) was shorter for the PB group than for the DZ/DPH group (median, 5 versus 9 minutes, p less than 0.06); the response latency (elapsed time from initiation of therapy to the end of the last convulsion) was also shorter for the PB group (median, 5.5 versus 15 minutes, p less than 0.10). The median cumulative convulsion time is between 0 and 14 minutes shorter for the PB regimen than for the DZ/DPH regimen (95% confidence interval). Similarly, the median response latency for the PB regimen is between 1 minute longer and 20 minutes shorter than that for the DZ/DPH regimen (95% confidence interval). The frequencies of intubation, hypotension, and arrhythmias were similar in the two groups. Eleven of 18 patients in the PB group responded to phenobarbital monotherapy. We conclude that the PB regimen is rapidly effective, comparable in safety, and enjoys certain practical advantages in comparison with the DZ/DPH regimen.
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PMID:Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. 327 82

Status Epilepticus (SE) is defined as an epileptic seizure which is so frequently repeated or so prolonged as to create a fixed and lasting epileptic condition. SE is observed in all age groups, but its frequency increases among younger children. Etiological factors vary with age. During infancy acute encephalopathies (infectious, anoxic-ischaemic, metabolic, etc.) are prevalent, while later non progressive encephalopathies are more frequent. Cryptogenic cases are present in all age groups, but "febrile" cases are observed before two years of age. Generalized forms are rare. The most frequent SE is Unilateral non alternating, which is observed exclusively among children. The semeiological diagnosis of SE with the help of EEG monitoring can be useful, since some forms of SE have constant etiological factors and prognosis. Since the condition of SE may cause brain damage or even endanger patient's life, immediate and adequate treatment is necessary. Diazepam and Phenytoin are particularly effective for stopping the seizures. A practical scheme for treatment is presented.
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PMID:[Status epilepticus in childhood]. 360 9

We reviewed 21 protocols for the evaluation and treatment of status epilepticus currently in use in pediatric residency programs. Guidelines were compared to determine variations in the recommendations for initial patient assessment, choice of anticonvulsant therapy, and instructions for medication administration. There was wide variation in recommendations for patient stabilization procedures and laboratory measurements. Fifteen different sequences of anticonvulsant administration were listed. The initial drug of choice was intravenous diazepam in 81% of the programs, in doses ranging from 0.1 to 0.75 mg/kg. The preference for the second-line anticonvulsant was divided equally between phenytoin and phenobarbital. Phenytoin was not mentioned at all in three (14%) of the protocols, while paraldehyde was included in 14 (66%). Instructions for paraldehyde administration were confusing, imprecise, and occasionally inappropriate. We conclude that there is no well-accepted approach to the management of status epilepticus in pediatric patients. Furthermore, the guidelines in current use frequently are incomplete and probably confusing to residents.
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PMID:Pediatric residency guidelines for management of status epilepticus. 361 37


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