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)

Lorazepam, a dichloro-3-hydroxy-1,4-benzodiazepine, has been shown to be a potent anticonvulsant in animal models of epilsepsy and has minimal depressant effects on respiration and circulation in humans. The effects of this compound were studied in status epilepticus. Twenty-five patients were given intravenous lorazepam during status epilepticus of varying cause. Four or 8 mg of the drug controlled status in 22 of the 25 patients. Although single seizures recurred in 5 of the 22 patients, none experienced recurrence of status during a prolonged follow-up period. Transient respiratory arrest occurred in 1 patient, but no other significant complications were observed. Studies of plasma drug levels suggest that most patients attain good seizure control at concentrations between 30 and 100 ng per milliliter. Clinical observations indicate that repetitive injections are not required for continuing control of seizures in patients whose seizures are initially controlled. Lorazepam appears to be an effective and safe drug for treatment of status epilepticus, with a duration of control longer than that achieved with diazepam.
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PMID:Lorazepam in status epilepticus. 4 12

We studied the efficacy, pharmacokinetics, and brain entry of lorazepam in the treatment of status epilepticus (SE) using a rat model of secondarily generalized convulsive SE. Lorazepam entered the bloodstream rapidly following intraperitoneal injection. Brain concentrations peaked 10 minutes after peak serum levels were achieved. Lorazepam remained in brain longer than in serum, leading to increasing brain: serum ratios over time once peak serum levels had been reached. Free lorazepam was 9.1% of the total concentration in serum, a fraction similar to that which has been reported for humans. The median effective dose for control of generalized tonic-clonic seizures in this model was 0.94 mg/kg, which would produce a serum concentration of 196 ng/ml. Rats in SE had higher serum lorazepam concentrations than controls given the same doses, but lower brain: serum ratios, perhaps due to lactic acidosis during SE. Our data confirmed clinical reports of lorazepam's effectiveness as a treatment for SE and suggest that a target serum concentration of 200 ng/ml should be effective in most cases and provide seizure protection for 24 hours following treatment.
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PMID:Lorazepam treatment of experimental status epilepticus in the rat: relevance to clinical practice. 234 20

Benzodiazepines are potent and effective drugs for the management of acute seizures and status epilepticus. Lorazepam, diazepam, and clonazepam have been the most widely studied of the benzodiazepines in the treatment of status epilepticus. In 47 studies of these drugs involving 1,455 patients, lasting control of status epilepticus was achieved in 79% of the patients. None of these benzodiazepines is clearly superior to another for the effective control of status epilepticus. Differences in pharmacokinetic parameters, therefore, will influence the choice of drug. All three benzodiazepines are lipid-soluble and enter the brain within seconds to minutes after intravenous administration. Diazepam, however, is very lipid-soluble and highly protein-bound and thus has a very large volume of distribution of unbound drug. As a result, the effective duration of action of diazepam in status epilepticus is only 20 to 30 min, whereas that of lorazepam, which has a much smaller volume of distribution of unbound drug, is at least several hours after a single intravenous injection. This allows the orderly administration of an antiepileptic drug for long-term seizure control after status epilepticus has been controlled. For this reason, lorazepam is preferable for the initial management of status epilepticus. Continuous intravenous infusion of diazepam has been used successfully in the management of some patients with status epilepticus refractory to initial treatment.
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PMID:Pharmacokinetics and clinical use of benzodiazepines in the management of status epilepticus. 267 May 37

A retrospective study was performed to compare intravenous lorazepam and intravenous diazepam in the treatment of status epilepticus. Forty-five episodes of status epilepticus in children between the ages of 2 weeks and 18 years were reviewed. Lorazepam and diazepam proved similar in efficacy of seizure control and incidence of adverse effects. The dose of lorazepam required to control status epilepticus ranged from 0.03 to 0.22 mg/kg with a mean of 0.11 mg/kg (S.D. = 0.05 mg/kg). Among children treated with lorazepam, only children younger than 2 years of age had respiratory depression which required intubation.
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PMID:Lorazepam versus diazepam for the treatment of status epilepticus. 324 74

The primary use of lorazepam, when administered intravenously (IV), has been in the treatment of acute attacks of anxiety and agitation. Recent studies have investigated its efficacy in patients with status epilepticus. The present study compared the efficacy and tolerability of lorazepam and clonazepam in the treatment of status epilepticus. Lorazepam, 4 to 10 mg IV, and/or clonazepam, 1 mg IV, was administered in 61 hospitalized epileptic patients. If needed, the dose of each agent was repeated in 20 minutes. Twenty-two patients were given lorazepam, nine were given clonazepam, and 30 were given both drugs at different times. Improvement in EEG was greater with lorazepam while the clinical symptoms responded more completely to clonazepam. Both drugs were most effective in patients with secondary generalized epilepsy. Drowsiness followed either drug. Psychomotor agitation followed either drug in 12% of patients.
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PMID:Comparative trial of intravenous lorazepam and clonazepam im status epilepticus. 612 Jul 63

Lorazepam was compared with diazepam for the treatment of status epilepticus in a double-blind, randomized trial. Seventy-eight patients with 81 episodes were enrolled. Patients received one or two doses of either 4 mg of lorazepam or 10 mg of diazepam intravenously. Seizures were controlled in 89% of the episodes treated with lorazepam and in 76% treated with diazepam. The times for onset of action of the medications did not differ significantly. Adverse effects occurred in 13% of the lorazepam-treated patients and in 12% of the diazepam-treated patients. Respiratory depression and arrest, the most frequent adverse effects, were treated symptomatically; no adverse sequelae were noted.
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PMID:Double-blind study of lorazepam and diazepam in status epilepticus. 613 Nov 48

The collective clinical data support the concept that lorazepam is highly effective for a broad range of seizure types, with the major inadequacy being in myoclonus, a seizure type typically highly resistant to other anticonvulsants as well. In addition to its effectiveness, lorazepam appears to have two other major advantages; a prolonged duration of action, which makes frequent or continuous administration unnecessary, and a high degree of freedom from serious side effects involving either the respiratory or cardiovascular system. Although experience at this time is insufficient to allow a firm statement concerning effective concentrations, such concentrations appear readily achievable in most patients with injections of 4 to 5 mg. Lorazepam appears to meet all the requirements of an anticonvulsant useful for treatment of status epilepticus and should prove to be a major drug in the treatment of this condition.
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PMID:Clinical studies of lorazepam in status epilepticus. 613 87

Twenty-one episodes of status epilepticus (SE) were each treated with 1 to 9 mg (mean, 4 mg) of intravenous lorazepam. All patients with generalized tonic-clonic ( GTC ) SE responded within 15 minutes. Nine (82%) of the 11 patients with episodes of partial SE with altered responsiveness responded poorly. Respiratory depression occurred in five instances (two requiring intubation) and was associated with transient loss of brain-stem reflexes, hypotension, and decorticate posturing in three cases. Generalized tonic-clonic SE was transformed into partial SE with altered responsiveness in three patients. In an additional four patients, marked lethargy developed. Lorazepam appears effective in controlling GTC SE but only occasionally effective in partial SE with altered responsiveness.
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PMID:Treatment of status epilepticus with lorazepam. 672 34

Lorazepam was compared with diazepam for the treatment of acute convulsions and status epilepticus in 102 children in a prospective, open, 'odd and even dates' trial. Convulsions were controlled in 76 per cent of patients treated with a single dose of lorazepam and 51 per cent of patients treated with a single dose of diazepam. Significantly fewer patients treated with lorazepam required additional anticonvulsants to terminate the seizure. Respiratory depression occurred in 3 per cent of lorazepam-treated patients and 15 per cent of diazepam-treated patients. No patient who received lorazepam required admission to the intensive care unit for either respiratory depression or persisting status epilepticus. Rectally administered lorazepam appeared to be particularly valuable (100 per cent efficacy) when venous access was not possible.
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PMID:Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus. 767 65

We treated nine refractory status epilepticus cases with high-dose intravenous lorazepam. We monitored the EEGs continuously, and lorazepam dosing was titrated to stop clinical and electrographic seizures. Lorazepam doses needed to terminate status epilepticus ranged from 0.3 to 9 mg/hr. Lorazepam did not cause hypotension. All patients survived. Outcome was complete recovery in two cases, moderate disability in four, and severe disability in three. These findings suggest high-dose intravenous lorazepam may be an effective alternative to pentobarbital for the treatment of severe status epilepticus.
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PMID:High-dose intravenous lorazepam for the treatment of refractory status epilepticus. 772 93


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