Pharmacological Prophylaxis Against Nerve Agent Poisoning

Bajgar, Jiří; Fusek, J.; Kassa, Jiřı́; Kuča, Kamil; Jun, Daniel

doi:10.1016/b978-0-12-800159-2.00066-x

Cited by 2 publications

(1 citation statement)

References 77 publications

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“…Fast ageing of phosphonylated AChE and poor efficacy of therapy have prompted the scientists to look for other means of counteracting NA poisoning like sheltering native AChE from phosphylation. Pre-exposure application (pretreatment), which enhances the efficacy of postexposure therapy, however, is to be distinguished from prophylaxis, which omits the application of post-exposure therapy (137)(138)(139)(140). Both protect native AChE from irreversible inhibition by NAs, but all NA exposure is highly likely to require subsequent therapy.…”

Section: Protection Of Native Ache From Inhibitionmentioning

confidence: 99%

Counteracting poisoning with chemical warfare nerve agents

Hrvat

Kovarik

2020

Archives of Industrial Hygiene and Toxicology

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Phosphylation of the pivotal enzyme acetylcholinesterase (AChE) by nerve agents (NAs) leads to irreversible inhibition of the enzyme and accumulation of neurotransmitter acetylcholine, which induces cholinergic crisis, that is, overstimulation of muscarinic and nicotinic membrane receptors in the central and peripheral nervous system. In severe cases, subsequent desensitisation of the receptors results in hypoxia, vasodepression, and respiratory arrest, followed by death. Prompt action is therefore critical to improve the chances of victim’s survival and recovery. Standard therapy of NA poisoning generally involves administration of anticholinergic atropine and an oxime reactivator of phosphylated AChE. Anticholinesterase compounds or NA bioscavengers can also be applied to preserve native AChE from inhibition. With this review of 70 years of research we aim to present current and potential approaches to counteracting NA poisoning.

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Section: Protection Of Native Ache From Inhibitionmentioning

confidence: 99%

Counteracting poisoning with chemical warfare nerve agents

Hrvat

Kovarik

2020

Archives of Industrial Hygiene and Toxicology

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Some Possibilities to Study New Prophylactics against Nerve Agents

Bajgar

Kassa

Kučera

et al. 2019

MRMC

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Nerve agents belong to the most dangerous chemical warfare agents and can be/were misused by terrorists. Effective prophylaxis and treatment is necessary to diminish their effect. General principles of prophylaxis are summarized (protection against acetylcholinesterase inhibition, detoxification, treatment “in advance” and use of different drugs). They are based on the knowledge of mechanism of action of nerve agents. Among different examinations, it is necessary to test prophylactic effectivity in vivo and compare the results with protection in vitro. Chemical and biological approaches to the development of new prophylactics would be applied simultaneously during this research. Though the number of possible prophylactics is relatively high, the only four drugs were introduced into military medical practice. At present, pyridostigmine seems to be common prophylactic antidote; prophylactics panpal (tablets with pyridostigmine, trihexyphenidyl and benactyzine), transant (transdermal patch containing HI-6) are other means introduced into different armies as prophylactics. Scavenger commercionally available is Protexia®. Future development will be focused on scavengers, and on other drugs either reversible cholinesterase inhibitors (e.g., huperzine A, gallantamine, physostigmine, acridine derivatives) or other compounds.

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Pharmacological Prophylaxis Against Nerve Agent Poisoning

Cited by 2 publications

References 77 publications

Counteracting poisoning with chemical warfare nerve agents

Counteracting poisoning with chemical warfare nerve agents

Some Possibilities to Study New Prophylactics against Nerve Agents

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