Journal of toxicology. Clinical toxicology
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J. Toxicol. Clin. Toxicol. · Jan 2002
The effect of the nitric oxide synthesis inhibitor L-NAME on amitriptyline-induced hypotension in rats.
Hypotension induced by tricyclic antidepressants is multifactorial. Previous animal experiments suggest a contribution from nitric oxide production. Our study aimed to evaluate the role of nitric oxide in amitriptyline-induced hypotension using N-nitro-L-arginine methyl ester, a nitric oxide synthesis inhibitor, and 3-morpholino sydnonimine, a nitric oxide donor, in anesthetized rats. ⋯ N-nitro-L-arginine methyl ester is found to be effective in temporarily improving hypotension and prolonging survival time but does not affect overall mortality. Because this effect was antagonized by 3-morpholino sydnonimine, nitric oxide production appears to contribute to the pathophysiology of amitriptyline-induced hypotension.
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J. Toxicol. Clin. Toxicol. · Jan 2002
Case ReportsA case of levetiracetam (Keppra) poisoning with clinical and toxicokinetic data.
Levetiracetam (Keppra) is a new anticonvulsant used to treat partial complex seizures that is also being investigated for its mood-stabilizing properties. Although its precise mechanism of action is unknown, levetiracetam does not appear to directly interact with the GABA system. We report the first intentional overdose with levetiracetam including clinical effects and serial serum concentrations. ⋯ In overdose, levetiracetam is sedating and causes respiratory depression, however, recovery is rapid with supportive care. This is the first reported case of levetiracetam overdose; serial serum concentrations suggest first-order elimination even at concentrations 10-40 fold higher than therapeutic.
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J. Toxicol. Clin. Toxicol. · Jan 2002
ReviewReview of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents.
The cholinesterase-inhibiting organophosphorus compounds referred to as nerve agents (soman, sarin, tabun, GF agent, and VX) are particularly toxic and are considered to be among the most dangerous chemical warfare agents. Included in antidotal medical countermeasures are oximes to reactivate the inhibited cholinesterase. Much experimental work has been done to better understand the properties of the oxime antidotal candidates including the currently available pralidoxime and obidoxime, the H oximes HI-6 and Hlö-7, and methoxime. ⋯ The H oximes appear to be very promising antidotes against nerve agents because they are able to protect experimental animals from toxic effects and improve survival of animals poisoned with supralethal doses. They appear more effective against nerve agent poisoning than the currently used oximes pralidoxime and obidoxime, especially in the case of soman poisoning. On the other hand, pralidoxime and especially obidoxime seem sufficiently effective to treat poisonings with organophosphorus insecticides that have relatively less toxicity than nerve agents.
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J. Toxicol. Clin. Toxicol. · Jan 2002
Trends in illicit drug emergencies: the emerging role of gamma-hydroxybutyrate.
Previously used as a general anesthetic, gamma-hydroxybutyrate is now used as a recreational drug. Not surprisingly, an increasing number of acute overdose cases requiring emergency medical care have been reported and described, especially in the United States. ⋯ Health authorities must be aware of the hazards of recreational gamma-hydroxybutyrate, and physicians must be cognizant of this recent cause of coma among youths presenting to the emergency departments.
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Acute valproic acid intoxication is an increasing problem, accounting for more than 5000 calls to the American Association of Poison Control Centers in 2000. The purpose of this paper is to review the pharmacology and toxicology of valproic acid toxicity. Unlike earlier antiepileptic agents, valproic acid appears to function neither through sodium channel inhibition nor through direct gamma-aminobutyric acid agonism, but through an indirect increase in regional brain gamma-aminobutyric acid levels. ⋯ Metabolic and hematologic derangements have also been described. Management of acute valproic acid ingestion requires supportive care and close attention to the airway. The use of controversial adjunctive therapies, including extracorporeal drug elimination and L-carnitine supplementation, will be discussed.