The role of diazepam in the treatment of nerve agent poisoning in a civilian population.
The main site of action of diazepam, as with other benzodiazepines, is at the GABA(A) receptor, although it has been suggested that some of the potentially beneficial actions of diazepam in nerve agent poisoning are mediated through other means. It is likely that convulsions may have long-term sequelae in the central nervous system, because of damage by anoxia and/or excitotoxicity. Numerous pharmacodynamic studies of the action of diazepam in animals experimentally poisoned with nerve agents have been undertaken. In nearly all of these, diazepam has been studied in combination with other antidotes, such as atropine and/or pyridinium oximes, sometimes in combination with pyridostigmine pretreatment. These studies show that diazepam is an efficacious anticonvulsant in nerve agent poisoning. There is considerable experimental evidence to support the hypothesis that diazepam (and other anticonvulsants) may prevent structural damage to the central nervous system as evidenced by neuropathological changes such as neuronal necrosis at autopsy. In instances of nerve agent poisoning during terrorist use in Japan, diazepam seems to have been an effective anticonvulsant. Consequently, the use of diazepam is an important part of the treatment regimen of nerve agent poisoning, the aim being to prevent convulsions or reduce their duration. Diazepam should be given to patients poisoned with nerve agents whenever convulsions or muscle fasciculation are present. In severe poisoning, diazepam administration should be considered even before these complications occur. Diazepam is also useful as an anxiolytic in those exposed to nerve agents.
Marrs
Timothy C
TC
Food Standards Agency, London and National Poisons Information Service, (Birmingham Centre), City Hospital, Birmingham, UK.
D000328:Adult; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002959:Civil Defense / Q000379:methods*; D003975:Diazepam / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D011041:Poisoning / Q000188:drug therapy* / Q000209:etiology; D011247:Pregnancy; D023481:Terrorism
D000931:Antidotes; D002619:Chemical Warfare Agents; D003975:Diazepam