US EPA

6545097 

Journal Article 

Medical treatment of acute poisoning with organophosphorus and carbamate pesticides 

Jokanović, M 

2009 

1 

Toxicology Letters
ISSN: 0378-4274
EISSN: 1879-3169 

190 

2 

107-115 

English 

19651196 

10.1016/j.toxlet.2009.07.025 

WOS:000270483900001 

Organophosphorus compounds (OPs) are 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 can be fatal and death is usually caused by respiratory failure. The mechanism of OP poisoning involves inhibition of acetylcholinesterase (AChE) leading to inactivation of the enzyme which has an important role in neurotransmission. AChE inhibition results in the accumulation of acetylcholine at cholinergic receptor sites, producing continuous stimulation of cholinergic fibers throughout the nervous systems. During more than five decades, pyridinium oximes have been developed as therapeutic agents used in the medical treatment of poisoning with OP. They act by reactivation of AChE inhibited by OP. However, they differ in their activity in poisoning with pesticides and warfare nerve agents and there is still no universal broad-spectrum oxime capable of protecting against all known OP. In spite of enormous efforts devoted to development of new pyridinium oximes as potential antidotes against poisoning with OP only four compounds so far have found its application in human medicine. Presently, a combination of an antimuscarinic agent, e.g. atropine, AChE reactivator such as one of the recommended pyridinium oximes (pralidoxime, trimedoxime, obidoxime and HI-6) and diazepam are used for the treatment of OP poisoning in humans. In this article the available data related to medical treatment of poisoning with OP pesticides are reviewed and the current recommendations are presented. 

Acetylcholinesterase; Antidotes; Atropine; Carbamates; Diazepam; HI-6; Medical treatment; Obidoxime; Organophosphorus compounds; Pesticides; Pralidoxime; Pyridinium oximes; Trimedoxime; Warfare nerve agents; activated carbon; aminotransferase; antidote; asoxime; atropine; benzodiazepine derivative; bis(pyridinium oxime) derivative; carbamate pesticide; chlorpyrifos; cholinesterase; cholinesterase inhibitor; diazepam; dimethoate; drug metabolite; ethoprop; fenamiphos; fenthion; malathion; monopyridinium oxime derivative; obidoxime; organophosphate pesticide; parathion methyl; pralidoxime; pralidoxime chloride; pralidoxime iodide; profenofos; pyridaphenthion; pyridinium oxime derivative; trimedoxime; unclassified drug; unindexed drug; absence of side effects; accommodation; acute toxicity; aminotransferase blood level; blood brain barrier; blurred vision; brain damage; burning sensation; cholestasis; cholinergic transmission; clinical assessment; clinical feature; clinical trial; conservative treatment; continuous infusion; convulsion; diplopia; disease severity; dizziness; drug blood level; drug brain level; drug effect; drug efficacy; drug induced headache; drug mechanism; drug megadose; drug overdose; drug penetration; drug structure; drug tolerability; enzyme active site; enzyme activity; enzyme reactivation; enzyme substrate; human; jaundice; liver toxicity; loading drug dose; low drug dose; morbidity; mortality; nausea; neurologic disease; nonhuman; pallor; paresthesia; priority journal; protein interaction; recommended drug dose; repeated drug dose; review; seizure; side effect; single drug dose; sore throat; stomach lavage; symptom; toxicokinetics; weakness; Acute Disease; Animals; Antidotes; Carbamates; Cholinesterase Inhibitors; Cholinesterase Reactivators; Humans; Organophosphorus Compounds; Pesticides; Poisoning