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  • Man  (2)
  • Cholinesterase reactivation  (1)
  • Neuronal cell death  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 341 (1990), S. 586-591 
    ISSN: 1432-1912
    Keywords: Cardiopulmonary arrest ; Resuscitation ; Nimodipine ; Neurological damage ; Neuronal cell death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Brain damage after resuscitation from cardiac arrest is believed to be related to calcium influx in ischaemic neurons and to postischaemic calcium-dependent vasospasm. We therefore evaluated the potentially protective effects of the calcium-entry blocker nimodipine in a cardiopulmonary arrest model in the rat. Male Wistar rats were anaesthetized with ketamine (group I) or hexobarbital (group II) and subjected to a KCl-induced cardiac arrest during 7 min (group I) or 12 min (group II). Five minutes after resuscitation, the rats were treated intravenously in a randomized and blind fashion. Group I received either saline or 1 μg · kg−1 · min −1 or 5 μg · kg−1 · min−1 of nimodipine and group II either saline or 1 μg · kg−1 · min−1 of nimodipine. Survival, occurrence of seizures and neurological status were assessed daily during 7 days after resuscitation. On day 7, the brains of the surviving rats were perfusion-fixed and a histopathological evaluation of the hippocampus was performed. Nimodipine, in the doses tested, had no beneficial influence on the 7 day survival rate, nor on the occurrence of seizures and the neurological and histopathological scores in the rats surviving after 7 days. With the highest dose of nimodipine, there was even a trend towards a decrease of the survival rate, probably related to the drug's hypotensive effect. Therefore, our data do not show a protective effect of nimodipine after cardiac arrest.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0738
    Keywords: Pralidoxime methylsulphate ; Organophosphorus agent ; Plasma concentration ; Cholinesterase reactivation ; Poisoning ; Man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We measured in nine patients, poisoned by organophosphorus agents (ethyl parathion, ethyl and methyl parathion, dimethoate, or brompphos), erythrocyte and serum cholinesterase activities, and plasma concentrations of the organophosphorus agent. These patients were treated with pralidoxime methylsulphate (ContrathionR), administered as a bolus injection of 4.42 mg.kg−1 followed by a continuous infusion of 2.14 mg.kg−1/h, a dose regimen calculated to obtain the presumed “therapeutic” plasma level of 4 mg.l−1, or by a multiple of this infusion rate. Oxime plasma concentrations were also measured. The organophosphorus agent was still detectable in some patients after several days or weeks. In the patients with ethyl and methyl parathion poisoning, enzyme reactivation could be obtained in some at oxime concentrations as low as 2.88 mg.l−1; in others, however, oxime concentrations as high as 14.6 mg.l−1 remained without effect. The therapeutic effect of the oxime seemed to depend on the plasma concentrations of ethyl and methyl parathion, enzyme reactivation being absent as long as these concentrations remained above 30 μg.l−1. The bromophos poisoning was rather mild, cholinesterases were moderately inhibited and increased under oxime therapy. The omethoate inhibited enzyme could not be reactivated.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0738
    Keywords: Pralidoxime methylsulphate ; Plasma concentration ; Organophosphorus poisoning ; Man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using pharmacokinetic data from healthy human volunteers in a bicompartmental pharmacokinetic model, a repeated dose scheme for pralidoxime methylsulphate (Contrathion®) was developed producing plasma levels remaining above the assumed “therapeutic concentration” of 4 mg·1−1. Using the same data, it was found that a concentration of 4 mg · 1−1 could also be obtained by a loading dose of 4.42 mg · kg−1 followed by a maintenance dose of 2.14 mg · kg−1 · h−1. In order to study the pharmacokinetic behaviour of pralidoxime in poisoned patients, this continuous infusion scheme was then applied in nine cases of organophosphorus poisoning (agents: ethyl parathion, ethyl and methyl parathion, dimethoate and bromophos), and the pralidoxime plasma levels were determined. The mean plasma levels obtained in the various patients varied between 2.12 and 9 mg·1−1. Pharmacokinetic data were calculated, giving a total body clearance of 0.57±0.271· kg−1· h−1 (mean ± SD), an elimination half-life of 3.44±0.90 h, and a volume of distribution of 2.77±1.451 ·kg−1.
    Type of Medium: Electronic Resource
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