Nerve agents anticholinesterase effects

Rapid advances in chemistry during the nineteenth and twentieth centuries, coupled with the success of mustard gas as a toxic weapon in World War I, attracted attention to the warfare potential of chemical agents. This led to support for research on lethal nerve agents during and immediately after World War II. The research was followed by the development of treatment methods, and prominent among these was the use of cholinesterase reactivators to reverse the lethal effects of anticholinesterase nerve gases. 

AH of the nerve agents under consideration are anticholinesterase compounds and induce accumulation of the neurotransmitter acetylcholine (ACh) at neural synapses and neuromuscular junctions by phosphorylating acetylcholinesterase (AChE). Depending on the route of exposure and amount absorbed, the PNS and/or CNS can be affected and muscarinic and/or nicotinic receptors may be stimulated. Interaction with other esterases may also occur, and direct effects to the nervous system have been observed. 

Anticholinesterase effects of nerve agent exposure can be characterized as muscarinic, nicotinic, or CNS. Muscarinic effects occur in the parasympathetic system and, depending on the amount absorbed, can be expressed as conjunctival congestion, miosis, ciliary spasm, nasal discharge, increased bronchial secretion, bronchoconstriction, anorexia, emesis, abdominal cramps, sweating, diarrhea, salivation, bradycardia, and hypotension. Nicotinic effects are those that... 

Acute side effects occur from therapeutic doses in 1 % of patients. However, an excessive dose of an anticholinesterase drug results in a cholinergic crisis. The condition results from stimulation of muscarinic receptors and depolarization of the motor end plate. Symptoms of salivation, lacrimation, diaphoresis, weakness, and respiratory failure may result. Therapeutic use of pyridostigmine should be discontinued in the presence of nerve agent poisoning, as it may exacerbate symptoms in certain exposures. 

Clinically, the most important effects of OP nerve agents are anticholinesterase actions. However, it should not be forgotten that OPs bind to a variety of enzymes, including esterases other than acetylcholinesterase, e.g. carboxylesterase, (long-chain fatty acid hydrolase), serine... 

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