Advice on assistance and protection provided by the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons: Part 1. On medical care and treatment of injuries from nerve agents

Timperley, Christopher M.; Forman, Jonathan E.; Abdollahi, Mohammad; Alamri, Abdullah; Baulig, Augustin; Benachour, Djafer; Borrett, Veronica; Cariño, Flerida A.; Geist, Michael; González, David; Kane, William M.; Kovarik, Zrinka; Martínez‐Álvarez, Roberto; Mourão, Nicia Maria Fusaro; Neffe, S.; Raza, S. K.; Rubaylo, Valentin; Suárez, Alejandra G.; Takeuchi, Koji; Tang, Cheng; Trifirò, Ferruccio; Straten, Francois Mauritz van; Vanninen, Paula; Vučinić, Slavica; Zaitsev, Vladimir; Zafar-uz-Zaman, M.; Zina, Mongia Saïd; Holen, Stian

doi:10.1016/j.tox.2019.01.004

Cited by 29 publications

(28 citation statements)

References 79 publications

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“…Poisoning from OP compounds produces three principal clinical syndromes: (a) acute cholinergic syndrome intermediate syndrome (IMS); and (c) OP-induced neuropathy (OPIDN) (Timperley and Tattersall, 2015;Lotti and Moretto, 2005). The acute cholinergic crisis develops within minutes to several hours after exposure, depending on the OP compound and the route of poisoning (Timperley et al, 2018a). Death can take place in a short time if life-threatening conditions, such as respiratory failure, are not treated rapidly and appropriately.…”

Section: Late Effects Of Organophosphorus Compoundsmentioning

confidence: 99%

“…The prognosis of repeated exposure to NA is more severe and the antidotal and supportive treatment must be as intensive as possible. Pyridostigmine bromide is a commonly advocated prophylactic antidote against NA poisoning (Timperley et al, 2018a). Unfortunately, it has several drawbacks.…”

Section: Summary Of Response To the Director General's Requestmentioning

confidence: 99%

“…Clinical approval from the FDA and European Medicines Agency (EMA) would be necessary prior a general recommendation. PANPAL consists of a reversible AChE inhibitor (pyridostigmine) to protect peripheral AChE from irreversible inhibition by NAs and two centrally-acting anticholinergic drugs (benactyzine and trihexyphenidyl; chemical structures provided in Timperley et al, 2018a) to increase slightly the dose of pyridostigmine bromide and to antagonise the overstimulation of central cholinergic muscarinic receptors. This combination introduced into the Czech Army shows higher efficacy than pyridostigmine alone to avoid or at least diminish the acute toxicity and to prevent delayed and long-lasting health effects from acute, prolonged and repeated exposure to NAs (Bajgar, 2009;Kassa, 2006).…”

Section: Summary Of Response To the Director General's Requestmentioning

confidence: 99%

“…Another approach to increase the resistance of humans to NAs and the efficacy of postexposure antidotal treatment of poisoning is to administer reactivators of NA-inhibited AChE in advance (Timperley et al, 2018a). In the Czech Republic, a special prophylactic antidote called TRANSANT (involving the oxime HI-6) was developed and introduced into service in the Czech Army (Bajgar, 2009).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…The SAB provided the Director-General with a response (OPCW 2014a) that recommended pretreatments and postexposure treatments that are available for countering the toxic effects of nerve agent (NA) chemical warfare agents (CWAs). This advice forms the substance of Part 1 of this series of papers (Timperley et al, 2018a) and that text should be consulted in parallel.…”

mentioning

confidence: 99%

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Advice on assistance and protection by the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons: Part 2. On preventing and treating health effects from acute, prolonged, and repeated nerve agent exposure, and the identification of medical countermeasures able to reduce or eliminate the longer term health effects of nerve agents

et al. 2019

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Section: Late Effects Of Organophosphorus Compoundsmentioning

confidence: 99%

Section: Summary Of Response To the Director General's Requestmentioning

confidence: 99%

Section: Summary Of Response To the Director General's Requestmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

mentioning

confidence: 99%

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Advice on assistance and protection by the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons: Part 2. On preventing and treating health effects from acute, prolonged, and repeated nerve agent exposure, and the identification of medical countermeasures able to reduce or eliminate the longer term health effects of nerve agents

et al. 2019

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Chemical Warfare Agents

Costanzi

2020

Kirk-Othmer Encyclopedia of Chemical Technology

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Chemical weapons are weapons that exploit the toxicity of chemicals to bring about death or harm. The toxic chemicals on which chemical weapons are based are known as chemical warfare agents. This article starts by providing some definitions of chemical weapons and chemical warfare agents as well an overview of key toxicology concepts and some notes on the physicochemical properties of the agents. Subsequently, it illustrates the chemistry, biochemistry, and medical countermeasures of the main classes of chemical warfare agents, namely vesicants, choking agents, blood agents, irritants, nerve agents, and centrally incapacitating agents.

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N‐methyl‐d‐aspartate receptors: Structure, function, and role in organophosphorus compound poisoning

Kolić,

Kovarik

2024

BioFactors

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Acute organophosphorus compound (OP) poisoning induces symptoms of the cholinergic crises with the occurrence of severe epileptic seizures. Seizures are induced by hyperstimulation of the cholinergic system, but are enhanced by hyperactivation of the glutamatergic system. Overstimulation of muscarinic cholinergic receptors by the elevated acetylcholine causes glutamatergic hyperexcitation and an increased influx of Ca2+ into neurons through a type of ionotropic glutamate receptors, N‐methyl‐d‐aspartate (NMDA) receptors (NMDAR). These excitotoxic signaling processes generate reactive oxygen species, oxidative stress, and activation of the neuroinflammatory response, which can lead to recurrent epileptic seizures, neuronal cell death, and long‐term neurological damage. In this review, we illustrate the NMDAR structure, complexity of subunit composition, and the various receptor properties that change accordingly. Although NMDARs are in normal physiological conditions important for controlling synaptic plasticity and mediating learning and memory functions, we elaborate the detrimental role NMDARs play in neurotoxicity of OPs and focus on the central role NMDAR inhibition plays in suppressing neurotoxicity and modulating the inflammatory response. The limited efficacy of current medical therapies for OP poisoning concerning the development of pharmacoresistance and mitigating proinflammatory response highlights the importance of NMDAR inhibitors in preventing neurotoxic processes and points to new avenues for exploring therapeutics for OP poisoning.

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Advice on assistance and protection provided by the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons: Part 1. On medical care and treatment of injuries from nerve agents

Cited by 29 publications

References 79 publications

Chemical Warfare Agents

N‐methyl‐d‐aspartate receptors: Structure, function, and role in organophosphorus compound poisoning

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