Pyridinium Oximes as Cholinesterase Reactivators in the Treatment of OP Poisoning

Publisher Summary This chapter describes the mechanisms of action of organophosphates (OPs) and the role of pyridinium oximes used as acetylcholinesterase (AchE) reactivators in the treatment of OP poisoning. OP compounds have been used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX, and others. Exposure to even small amounts of an OP compound can be fatal; death is usually caused by respiratory failure resulting from paralysis of the diaphragm and intercostal muscles, depression of the brain respiratory center, bronchospasm, and excessive bronchial secretions. Signs and symptoms of acute poisoning with anticholinesterase agents are predictable from their biochemical mechanism of action and are directly related to the levels of AChE activity. Three types of effects evident in these poisonings are muscarinic, nicotinic, and central signs and symptoms. The duration of effects is determined mainly by the properties of the compound: its liposolubility, the stability of the OP–AChE complex, and whether it is reactivatable after the use of cholinesterase reactivators. The signs and symptoms of poisoning with direct inhibitors appear quickly during or after exposure, while those with indirect inhibitors appear slowly and last longer, even up to several days after cessation of exposure. Clinical diagnosis is relatively simple and is based on medical history, circumstances of exposure, and the presence of clinical symptoms of poisoning. Confirmation of diagnosis can be made by measurement of red blood cell AChE or plasma ChE.