Anticholinesterases as antidotes to envenomation of rats by the death adder (Acanthophis antarcticus).
ABSTRACT 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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ABSTRACT: Objective. Most snakebite deaths occur prior to hospital arrival; yet inexpensive, effective, and easy to administer out-of-hospital treatments do not exist. Acetylcholinesterase inhibitors can be therapeutic in neurotoxic envenomations when administered intravenously, but nasally delivered drugs could facilitate prehospital therapy for these patients. We tested the feasibility of this idea in experimentally envenomed mice. Methods. Mice received intraperitoneal injections of Naja naja venom 2.5 to 10 times the estimated LD50 and then received 5 μ L neostigmine (0.5 mg/mL) or 5 μ L normal saline by nasal administration. Animals were observed up to 12 hours and survivors were euthanized. Results. 100% of control mice died. Untreated mice injected with 2.5× LD50 Naja naja died at average 193 minutes after injection, while 10 of 15 (67%) of treated mice survived and were behaviorally normal by 6 hours (P < 0.02). In the 5× LD50 group, survival was prolonged from 45 minutes to 196 minutes (P = 0.01) and for 10× LD50 mice, survival increased from 30 to 175 minutes (P < 0.02). Conclusion. This pilot suggests that intranasal drugs can improve survival and is the first direct demonstration that such an approach is plausible, suggesting means by which treatment could be initiated before reaching the hospital. Further investigation of this approach to neurotoxic and other types of envenomation is warranted.Journal of Tropical Medicine 05/2014; 2014:131835. DOI:10.1155/2014/131835
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ABSTRACT: Key Clinical Message Neurotoxic snake envenomation can result in respiratory failure and death. Early treatment is considered important to survival. Inexpensive, heat-stable, needle-free, antiparalytics could facilitate early treatment of snakebite and save lives, but none have been developed. An experiment using aerosolized neostigmine to reverse paralysis suggests how early interventions could be developed.10/2013; 1(1). DOI:10.1002/ccr3.3
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ABSTRACT: Acanthophis genus (i.e. death adders) and the Naja genus (i.e. cobras) belong to the family elapidae. The current study compared the in vitro cytotoxicity of venoms from four Acanthophis spp. and three Naja spp. on rat aortic smooth muscle cells, A7r5, and rat skeletal muscle cells, L6. The ability of CSL death adder antivenom and SAIMR antivenom, for Acanthophis spp. and Naja spp. venom respectively, to negate the cytotoxicity was also examined. A cell proliferation assay was used to determine cell viability following treatment with venom in the presence or absence of antivenom. Sigmoidal growth curves were obtained, and IC(50) values were determined. Acanthophis spp. and Naja spp. venoms produced concentration-dependent inhibition of cell proliferation in both cell lines. Naja spp. venoms were significantly more cytotoxic than the most potent Acanthophis venom (i.e. A. antarcticus) in both cell lines. Naja spp. venoms also displayed higher sensitivity in L6 cells. SAIMR antivenom significantly inhibited the cytotoxic actions of all Naja spp. venoms in both A7r5 and L6 cells. However, death adder antivenom (CSL Ltd) was unable to negate the cytotoxic effects of Acanthophis spp. venoms. Concentrations of the predominantly cytotoxic Naja spp. venoms used were approximately three times less than the predominantly neurotoxic Acanthophis spp. venoms. SAIMR antivenom was partially effective in neutralising the effects of Naja spp. venoms. Death adder antivenom (CSL Ltd) was not effective in negating the cytotoxic effects of venom from Acanthophis spp. These results indicate that the cell-based assay is suited to the examination of cytotoxic snake venoms and may be used in conjunction with organ bath experiments to pharmacologically characterise snake venoms. Furthermore, the results suggest that the use of a skeletal muscle cell line is likely to be more clinically relevant for the examination of cytotoxic snake venoms.Journal of pharmacological and toxicological methods 03/2011; 63(2):137-42. DOI:10.1016/j.vascn.2010.09.001 · 2.15 Impact Factor