Anticholinesterases as antidotes to envenomation of rats by the death adder (Acanthophis antarticus)

Department of Physiology, University of Adelaide, South Australia.
Toxicon (Impact Factor: 2.49). 02/1994; 32(1):35-9. DOI: 10.1016/0041-0101(94)90019-1
Source: PubMed


The purpose of this study was to find an antidote against death adder envenomation that can be used in cases of emergency, when antivenoms are not readily available (Papua New Guinea and the Australian outback). Such an antidote should allow bite victims to survive until established treatment is possible. Death adder venom is thought to act postsynaptically at the neuromuscular junction to reduce responses to acetylcholine. This causes severe flaccid paralysis and finally death, which is usually a consequence of respiratory failure. Albino Wistar rats were injected with a lethal dose of crude death adder venom. At the onset of severe envenomation symptoms, anticholinesterases (neostigmine and edrophonium) in conjunction with atropine sulfate were administered. At the minimum lethal dose (0.15 mg/kg) all animals survived as a result of the anticholinesterase treatment. The expected survival time of animals subjected to higher venom doses was significantly extended. These results indicate that death adder bite victims may gain valuable time, if anticholinesterases can be administered during the initial critical stage of envenomation.

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    • "The present study tested the hypothesis that neostigmine, given IN, would be an effective initial treatment of Naja naja envenomed mice. The early use of AChEIs leads to a considerable increase in the LD50 in mice and rats having undergone experimental envenomation [15, 16]. Our study is distinguished from those by the replacement of parenteral neostigmine with topically applied IN neostigmine. "
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    ABSTRACT: Thirty-two patients with enzyme-immunoassay-proven death adder (Acanthophis sp.) bites were studied in Port Moresby, Papua New Guinea. Eighteen were envenomed; local signs were rare and none had incoagulable blood, but all except one had signs of neurotoxicity. Five (27.7%) envenomed patients required intubation and ventilation. One patient developed renal failure, previously undescribed following death adder bites. Laboratory investigations showed mild prolongation of prothrombin and partial thromboplastin times in some patients. In vitro studies showed that the venom contains anticoagulant activity, but does not cause fibrinogenolysis. In contrast to taipan envenoming, neurotoxicity did not progress after antivenom administration, and there was reversal of neurotoxicity, evident within 6 h, in three severely envenomed patients treated less than 12 h after the bite. One patient treated with antivenom and anticholinesterases had the most dramatic response to treatment; the optimum management of bites by this species may include prompt treatment with both antivenom and anticholinesterases in addition to effective first aid.
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