Comparative efficacy of diazepam and avizafone against sarin-induced neuropathology and respiratory failure in guinea pigs: Influence of atropine dose

Taysse, L.; Calvet, J; Christin, Didier; Delamanche, S.; Breton, P.

doi:10.1016/s0300-483x(03)00086-6

Cited by 18 publications

(5 citation statements)

References 18 publications

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“…Respiratory response to soman typically begins with hyperpnoea, which is followed by dyspnoea, hypopnoea and finally respiratory failure. Another study has been conducted by using guinea‐pigs in sarin poisoning (Taysse et al 2003). The results have shown that respiratory distress was revealed by a significant decrease in minute ventilation, tidal volume and frequency rate due to an apnoeic state.…”

Section: Discussionmentioning

confidence: 99%

Effect of Sodium Bicarbonate in Rats Acutely Poisoned with Dichlorvos

Stefanovic

Antonijević

Bokonjić

et al. 2006

Basic Clin Pharma Tox

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The development of effective antidotes against organophosphates such as dichlorvos has been a persistent challenge over the past decades. Therapy of organophosphate poisoning is based on the administration of atropine and oxime as standard antidotes. The present study was undertaken to evaluate the ability of sodium bicarbonate to improve protective effects of standard antidotes in rats poisoned with dichlorvos. The aim of this experiment was to establish the correlation between protective effects and biochemical parameters relevant for acid-base status. In order to examine the protective effect of both standard antidotes and their combinations, groups of experimental animals were poisoned subcutaneously with increasing doses of dichlorvos. Immediately thereafter, rats were treated with atropine 10 mg/kg intramuscularly, oximes 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally. These antidotes were administered either as single doses or in combinations. In the biochemical part of the experiments, rats were poisoned with dichlorvos 1.3 LD 50 (10.64 mg/kg) subcutaneously and immediately thereafter treated with atropine 10 mg/kg intramuscularly, oximes (trimedoxime or obidoxime) 10 mg/kg intramuscularly and sodium bicarbonate 3 mmol/kg intraperitoneally either as single doses or in combinations. Parameters relevant for acid-base status were measured 10 minutes after the administration of antidotes. The results of our study indicate that addition of sodium bicarbonate to standard antidotes significantly improves protective effects of atropine, obidoxime and trimedoxime. Correlation between protection and biochemical outcome is clearly evident when sodium bicarbonate is being added to atropine.

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Section: Discussionmentioning

confidence: 99%

Effect of Sodium Bicarbonate in Rats Acutely Poisoned with Dichlorvos

Stefanovic

Antonijević

Bokonjić

et al. 2006

Basic Clin Pharma Tox

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“…Coupled with previous evidence that diazepam reduces the long-term effects of OP exposure, our findings strongly support its use in the setting of severe OP poisoning, including as an induction agent for intubation, even in the absence of overt convulsions. 3,11,13,14,19 We believe that longer acting benzodiazepines also should be used prophylactically in patients at risk for short-and longterm sequelae, including CNS-mediated respiratory depression, seizures, cognitive dysfunction, and neuropsychiatric effects. The use of ketamine appears to be unwarranted.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 In addition to oximes, mechanical ventilation, and supportive care, the current antidotal approach emphasizes the antimuscarinic agent atropine, at times combined with centrally acting benzodiazepines, which act synergistically in animal models of severe poisoning. 3,[10][11][12][13][14][15] This approach ignores the distinction between the peripheral and central sites of action of atropine, which crosses the blood-brain barrier to act centrally but is titrated against peripheral manifestations. 16 The resultant large doses of atropine may exceed several hundred milligrams, raising concerns regarding an overshoot central anticholinergic delirium.…”

mentioning

confidence: 99%

Multiple Centrally Acting Antidotes Protect against Severe Organophosphate Toxicity

Sivilotti

Bird

et al. 2006

Academic Emergency Medicine

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“…In the latter case, a watersoluble prodrug, avizafone, is used. This is a lysine conjugate of diazepam which is rapidly hydrolysed in the body to release the active drug (21,231,(252)(253)(254)(255). Given sufficient warning, the therapy can be supported by a pretreatment using a reversible carbamate AChE inhibitor (pyridostigmine), the aim being to shield a proportion of AChE from irreversible inhibition by nerve agents (251).…”

Section: Treatment Of Op Seizuresmentioning

confidence: 99%

Seizure activity post organophosphate exposure

Tattersall¹

2009

Front Biosci

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Electrographic seizures are a feature of organophosphate anticholinesterase intoxication. Clinical studies of pesticide poisonings suggest that seizures are more common in children than in adults. Since flaccid paralysis, a characteristic sign of organophosphate poisoning, can mask convulsions, the most reliable indicator of seizures is the electroencephalogram, but this has not been widely used in clinical studies. Seizures can rapidly progress to status epilepticus, contributing to mortality and, in survivors, to neuronal damage and neurological impairment. Anticonvulsant drugs can significantly reduce the lethal and toxic effects of these compounds. A benzodiazepine, usually diazepam, is the treatment currently indicated for control of seizures. Animal studies have indicated that the early phase of seizure activity (0-5 min after seizure onset) is purely cholinergic, predominantly involving muscarinic mechanisms. Seizure activity subsequently progresses through mixed cholinergic and noncholinergic modulation (5-40 min) into a final noncholinergic phase. Neuropathology caused by seizures is most likely associated with glutamatergic excitotoxicity. Future prospects for improved treatments include new benzodiazepines, glutamate receptor antagonists, antimuscarinics with additional antiglutamatergic activity and adenosine receptor antagonists.

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Comparative efficacy of diazepam and avizafone against sarin-induced neuropathology and respiratory failure in guinea pigs: Influence of atropine dose

Cited by 18 publications

References 18 publications

Effect of Sodium Bicarbonate in Rats Acutely Poisoned with Dichlorvos

Effect of Sodium Bicarbonate in Rats Acutely Poisoned with Dichlorvos

Multiple Centrally Acting Antidotes Protect against Severe Organophosphate Toxicity

Seizure activity post organophosphate exposure

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