The effect of atropine dosage on the efficacy of other pretreatment and treatment medical countermeasures for nerve agent intoxication

Koplovitz, Irwin; Schulz, Susan; Railer, Roy; Sigler, Melinda; Kelleher, Cristin; Shutz, Michael

doi:10.1016/j.tox.2006.04.020

Cited by 6 publications

(2 citation statements)

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“…As a consequence, pretreatments are uncommon, and early treatments are usually limited to less effective measures such as emptying the stomach of the patient or administering activated charcoal. The standard drug treatments are based, generally, on anticholinergic therapies using atropines. , Atropines antagonize the central and muscarinic effects of neurotransmitters by blocking these receptors. However, atropines do not bind to nicotinic receptors; hence, muscular weaknesses, including respiratory muscle weakness, are not affected .…”

Section: Introductionmentioning

confidence: 99%

Investigation of Lysine-Functionalized Dendrimers as Dichlorvos Detoxification Agents

Durán-Lara

Marple²,

Giesen³

et al. 2015

Biomacromolecules

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Lysine-containing polymers have seen broad application due to their amines' inherent ability to bind to a range of biologically relevant molecules. The synthesis of multiple generations of polyester dendrimers bearing lysine groups on their periphery is described in this report. Their hydrolytic stabilities with respect to pH and time, their toxicity to a range of cell lines, and their possible application as nano-detoxification agents of organophosphate compounds are all investigated. These zeroth-, first-, and second-generation water-soluble dendrimers have been designed to bear exactly 4, 8, and 16 lysine groups, respectively, on their dendritic periphery. Such monodisperse bioactive polymers show potential for a range of applications including drug delivery, gene delivery, heavy metal binding, and the sequestration of organic toxins. These monodisperse bioactive dendrimers were synthesized using an aliphatic ester dendritic core (prepared from pentaerythritol) and protected amino acid moieties. This library of lysine-conjugated dendrimers showed the ability to efficiently capture the pesticide dichlorvos, confirming the potential of dendrimer-based antidotes to maintain acetylcholinesterase activity in response to poisoning events.

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Section: Introductionmentioning

confidence: 99%

Investigation of Lysine-Functionalized Dendrimers as Dichlorvos Detoxification Agents

Durán-Lara

Marple²,

Giesen³

et al. 2015

Biomacromolecules

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“…Currently, pralidoxime (2-PAM), trimedoxime (TMB-4), obidoxime and HI-6 ( Fig. 2) are used as AChE reactivators in the treatment of OP poisoning (Namba and Hiraki, 1958;Luettringhaus and Hagedorn, 1964;Hagedorn et al, 1969) along with atropine (as antimuscarinic agent) (Koplovitz et al, 2007) and diazepam (anticonvulsant drug) (Marrs, 2003).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in vitro screening of N-phenacylpyridinium oximes as reactivators of organophosphorus (OP)-inhibited electric eel acetylcholinesterase (AChE)

et al. 2015

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Pyridinium oxime-based drugs are generally used in the treatment of acute organophosphorus (OP) nerve agent poisoning. In this regard, a series of monopyridinium oximes bearing substituted phenacyl moieties as side chain were synthesized and screened for their in vitro reactivation efficacies against electric eel acetylcholinesterase (AChE) inhibited by OP inhibitors such as DFP, sarin and VX. The results of the in vitro reactivation data of the synthesized compounds were compared to standard antidotes 2-PAM and obidoxime. Among the synthesized compounds, 1a, 2a, 7a, 8a, 11a, 12a, 13a, 14a and 16a have shown better reactivation efficacy than 2-PAM and obidoxime against VX-inhibited AChE. Oximes 8a, 8b, 11a and 12a were at par with obidoxime in the reactivation of sarin-inhibited AChE. The pKa values for all the oximes were determined and correlated with their observed reactivation potential.

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The potential role of bioscavenger in the medical management of nerve-agent poisoned casualties

Rice

Mann

Armstrong

et al. 2016

Chemico-Biological Interactions

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The provision of effective Medical Countermeasures (MedCM) for all agents and routes of exposure is a strategic goal of defence research and development. In the case of military autoinjector-based therapies for nerve agent poisoning, current treatment effectiveness is limited by the oxime reactivator being effective against only certain agents, by rapid clearance times of the drugs and because the doses may not be optimal for treatment of severe poisoning. Prolonged poisoning by nerve agents entering the body through the skin is also challenging. Since casualty handling timelines have reduced significantly in recent years, it may be sufficient for first aid therapy to provide protection for only a few hours until further medical treatment is available. Therefore, the traditional evaluation of first aid therapy in animal models of survival at 24 h may not be appropriate. At various echelons of medical care, further therapeutic interventions are possible. The current basis for the medical management of nerve-agent poisoned casualties is derived mainly from clinical experience with pesticide poisoning. Adjunct therapy with a bioscavenger (such as human butyrylcholinesterase (huBChE)), could have utility as a delayed intervention by reducing the toxic load. It has previously been demonstrated that huBChE is an effective post-exposure therapy against percutaneous VX poisoning. It is recommended that the scope of animal models of nerve agent MedCM are extended to cover evaluation of both first aid MedCM over significantly reduced timescales, and subsequent supportive therapeutic and medical management strategies over longer timescales. In addition to bioscavengers, these strategies could include repeated combined and individual therapy drugs to alleviate symptoms, other classes of drugs or ventilatory support. Crown Copyright [2016] Published by Elsevier Ireland Ltd. This is an open access article under the Open Government Licence (OGL) (http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/).

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The effect of atropine dosage on the efficacy of other pretreatment and treatment medical countermeasures for nerve agent intoxication

Cited by 6 publications

References 0 publications

Investigation of Lysine-Functionalized Dendrimers as Dichlorvos Detoxification Agents

Investigation of Lysine-Functionalized Dendrimers as Dichlorvos Detoxification Agents

Synthesis and in vitro screening of N-phenacylpyridinium oximes as reactivators of organophosphorus (OP)-inhibited electric eel acetylcholinesterase (AChE)

The potential role of bioscavenger in the medical management of nerve-agent poisoned casualties

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