Countermeasures in organophosphorus intoxication: pitfalls and prospects. (July 2022)

• Record Type: Journal Article
• Authors: Gorecki, Lukas; Soukup, Ondrej; Korabecny, Jan
• Is Part Of: Trends in pharmacological sciences. Volume 43:Number 7(2022)
• Page Start: 593
• Page End: 606
• Publication Date: 2022-07
• Subjects: acetylcholinesterase -- atropine -- insecticides -- nerve agents -- organophosphorus -- oxime reactivators; Pharmacology -- Periodicals; Pharmacology -- trends -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Electronic journals; Periodicals; 615.1
• DOI: 10.1016/j.tips.2022.04.008
• Languages: English
• ISSNs: 0165-6147

Abstract

Abstract : High lethality, fast action, and simple synthesis make nerve agents (NAs) the most dreaded chemical weapons (CWs) of mass destruction in the world. Disturbances of the autonomic nervous system and neuromuscular junction (NMJ) by NAs and organophosphorus (OP) insecticides lead to cholinergic crisis and skeletal muscle paralysis. Current medical intervention has remained mostly unchanged since their first discovery in the 1950s. Within this overview, we have followed their development, clinical successes, and failures and discuss the major demerits of available antidotes. In current times, with precision medicine becoming increasingly relevant in various fields of medicine, the antidotal approach should be broadened to better cope with individual cases of NA intoxication. When possible, countermeasures could be targeted directly to achieve a better patient prognosis. As the threat of NA misuse and accidental cases of OP insecticide intoxication are still omnipresent, advancement of intervention expertise and further research in this field should be supported. Highlights: Organophosphorus (OP) intoxication should not be considered as a single condition, treatable by a universal antidotal cocktail, but rather each case should be handled individually. Medical intervention should be applied on the understanding that the toxicity varies widely among nerve agents as well as pesticides. Since the first occurrence in the 1950s, the antidotal cocktail has remained almost unchanged, despite possessing several major drawbacks. The antidotal armamentarium should be expanded in each country to adopt precision medicine principles in OP compound (OPC) countermeasure. Recent use of A-agents (Novichoks) has shown that developing novel and even more effective chemical weapons is still viable in the modern era.