Anticholinesterases cholinesterase agent effects

Individuals with hereditary low plasma cholinesterase levels (Kalow 1956 Lehman and Ryan 1956) and those with paroxysmal nocturnal hemoglobinuria, which is related to abnormally low levels of erythrocyte acetylcholinesterase (Auditore and Hartmann 1959), would have increased susceptibility to the effects of anticholinesterase agents such as methyl parathion. Repeated measurements of plasma cholinesterase activity (in the absence of organophosphate exposure) can be used to identify individuals with genetically determined low plasma cholinesterase. 

Because anticholinesterase agents also inhibit plasma pseudo-ChE, they will potentiate the effects of succinylcholine by inhibiting its breakdown. This is important, for example, when succinylcholine is to be employed in patients who have previously received cholinesterase inhibitors for the treatment of myasthenia gravis or glaucoma. 

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. 

The therapeutic action of oximes resides largely In their capacity to reactivate cholinesterases without contributing markedly toxic actions of their own at recommended or usual doses. Other actions may contribute to their effectiveness they may react directly with the anticholinesterase agent,4 4 block its reaction with cholinesterase, 0 modulate the release of acetylcholine, 30,74 block acetylcholine s agonistic activity... 

Anticholinergic agents are typically used as treatment for anticholinesterase poisoning and vice versa. Riysostlgmlne, tetrahydroamlnoacrldlne, and other cholinesterase Inhibitors were used successfully as antidotes In several dozen subjects. The demonstration of physosclgmlne s effectiveness led to the first controlled study of Its ability to reverse delirium due to scopolamine (31). Riysosclgmlne has been used to overcome anticholinergic toxicity. 

Reversal of this type of neuromuscular block can be achieved with anticholinesterase drugs, such as neostigmine, which prevent the destruction by cholinesterase of acetylcholine released at nerve endings, allow the concentration to build up and so reduce the competitive effect of a blocking agent. 

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