Organophosphates⧸Nerve Agent Poisoning: Mechanism of Action, Diagnosis, Prophylaxis, And Treatment

Organic compounds of phosphorus show a broad variety of biological properties. They can be irritating, mutagenic, teratogenic or carcinogenic, nephrotoxic, myelotoxic, or pneumotoxic. Some of these compounds damage the pancreas and testes, others can influence the nervous system psychotomimetically or in a depressive manner, or they have delayed neurotoxic effects. Organic phosphorus (OP)/nerve agents are still considered important chemicals acting on living organisms and are widely used. They are characterized according to their action as compounds influencing cholinergic nerve transmission via inhibition of AChE. The symptoms of intoxication comprise nicotinic, muscarinic, and central symptoms; for some OP/nerve agents, a delayed neurotoxicity is observed. Cholinesterases are characterized as the main enzymes involved in the toxic effect of these compounds, including molecular forms. The activity of both enzymes is influenced by inhibitors and other factors, such as pathological stated in this chapter. The term “prophylaxis” as used in this chapter is limited to medical countermeasures applied relatively shortly before penetration of a toxic agent into the organism. Diagnosis of OP poisoning is based on clinical signs and cholinesterase determination using the most suitable material for laboratory diagnostics—the blood. Basic principles of the treatment of nerve agent OP poisoning are described. They are based on the administration of anticholinergics as a symptomatic treatment, cholinesterase reactivators as a causal treatment as first aid and medical treatment, and anticonvulsants, preferably diazepam though some other effective benzodiazepines are available. Future trends in the complex research of these compounds that is important not only for the treatment of intoxication, but also for the quantitative and qualitative increase of our knowledge of toxicology, neurochemistry, neuropharmacology, clinical biochemistry, and analytical chemistry in general are characterized in this chapter.