A systems dynamics approach to the efficacy of oxime therapy for mild exposure to sarin gas
Keywords:system dynamics, oxime therapy, nerve agents, physiologically based pharmacokinetics, model
The use of nerve agents such as sarin is as much a threat today as any other time in our history. The events in Syria in 2013 are proof of this. “The Obama administration asserted Sunday for the first time that the Syrian government used the nerve gas sarin to kill more than 1,400 people (August 21, 2013) in the world's gravest chemical weapons attack in 25 years.” With these recent events clear in our mind, we must focus on the horrific nature of these chemical agents to devise a strategy that will enable first responders to counteract these insidious chemicals. This paper presents research on a physiologically based pharmacokinetic model to determine whether the current treatment protocol prescribed by the Center for Disease Control (CDC) and the US Army is effective in treating victims suffering from acute exposure symptoms. The model was used to determine what treatment should be used for victims suffering from mild exposure symptoms. The results indicate that the current CDC and US Army treatment is effective, but treatment with oxime therapy was not effective in alleviating symptoms of mild exposure. By applying these results, an effective treatment protocol was developed.
The President Barack Obama: United States National Security Strategy 2010. Available at https://www.whitehouse.gov/sites/default/files/rss_viewer/national_security_strategy.pdf. Accessed February 10, 2014.
Whitlock C, O'Keefe E: Sarin gas used in Syria attack, Kerry says. Washington Post. September 1, 2013. Available at https://www.washingtonpost.com/world/national-security/sarin-gas-usedin-syria-attack-kerry-says/2013/09/01/4b657cb8-1304-11e3-b18ae00deecb3b8e_story.html. Accessed March 10, 2014.
Yanagisawa N, Morita H, Nakajima T, et al.: Sarin poisoning in Matsumoto, Japan. Lancet. 1995; 346(8970): 290-293.
Smart JK: History of chemical and biological warfare: An American perspective. In Medical Aspects of Chemical and Biological Warfare. Washington, DC: Office of the Surgeon General, 1997: 9-86.
Szinicz L, Worek F, Thiermann H, et al.: Development of antidotes: Problems and strategies. Toxicology. 2007; 233(1): 23-30.
Worek F, Szinicz L, Eyer P, et al.: Evaluation of oxime efficacy in nerve agent poisoning: Development of a kinetic-based dynamic model. Toxicol Appl Pharmacol. 2005; 209(3): 193-202.
Cannard K: The acute treatment of nerve agent exposure. J Neurol Sci. 2006; 249(1): 86-94.
Rebmann T, Clements BW, Bailey JA, et al.: Organophosphate antidote auto-injectors vs. traditional administration: A time motion study. J Emerg Med. 2009; 37(2): 139-143.
Wali FA, Suer AH, Dark CH, et al.: Atropine sulphate enhances neuromuscular transmission in the rat. Acta Anaesthesiol Scand. 1987; 31(7): 587-592.
Karalliedde L: Organophosphorus poisoning and anaesthesia. Anaesthesia. 1999; 54: 1073-1088.
Seaman GG: Optimization of Therapeutic Strategies for Organophosphate Poisoning. Wright Patterson Base, OH: Air Force Institute of Technology (AU), 2008.
Gearhart JM, Jepson GW, Clewell HJ, et al.: Physiologically based pharmacokinetic model for the inhibition of acetylcholinesterase by organophosphate esters. Environ Health Perspect. 1994; 102(suppl (11)): 51-60.
Szinicz L: History of chemical and biological warfare agents. Toxicology. 2005; 214(3): 167-181.
Somani SM, Romano JA: Chemical Warfare Agents: Toxicity at Low Levels. Boca Raton, FL: CRC Press, 2001.
Okumura T, Takasu N, Ishimatsu S, et al.: Report on 640 victims of the Tokyo subway sarin attack. Ann Emerg Med. 1996; 28(2): 129-135.
Eyer P, Szinicz L, Thiermann H, et al.: Testing of antidotes for organophosphorus compounds: Experimental procedures and clinical reality. Toxicology. 2007; 233(1-3): 108-119.
Buckley NA, Roberts D, Eddleston M: Overcoming apathy in research on organophosphate poisoning. BMJ. 2004; 329: 1231-1233.
Fox SI: Human Physiology. Boston: McGraw-Hill, 2004.
Sidell FR, Takafuji ET, Franz DR: Medical Aspects of Chemical and Biological Warfare. Falls Church, VA: Office of the Surgeon General (Army), 1997.
U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) (ed.): Medical Management of Chemical Casualties Handbook. 4th ed. Aberdeen Proving Ground, MD: USAMRICD, 2007.
Eddleston M, Eyer P, Worek F, et al.: Pralidoxime in acute organophosphorus insecticide poisoning-A randomised controlled trial. Plos Med. 2009; 6(6): e1000104.
Holder CA: Development of Optimized Guidelines for Therapeutic Strategies for Organophosphate Poisoning. Wright Patterson Base, OH: Air Force Institute of Technology (AU), 2011.
Atsdr.cdc.gov: ATSDR—Medical Management Guidelines (Mmgs): Nerve agents (GA, GB, GD, VX). Available at http://www.atsdr.cdc.gov/MMG/MMG.asp?id=523&tid=93. Accessed May 2, 2014.
Gearhart JM, Robinson PJ, Jakubowski EM: Physiologically based pharmacokinetic modeling of chemical warfare agents. In Gupta RC (ed.): Handbook of Toxicology of Chemical Warfare Agents. San Diego, CA: Academic Press, 2009: 791-798, chap 51.
Hoang KT: Physiologically based pharmacokinetic models: Mathematical fundamentals and simulation implementations. Toxicol Lett. 1995; 79(1-3): 99-106.
Maxwell DM, Lenz DE, Groff WA, et al.: The effects of blood flow and detoxification on in vivo cholinesterase inhibition by soman in rats. Toxicol Appl Pharmacol. 1987; 88(1): 66-76.
Timchalk C, Nolan RJ, Mendrala AL, et al.: A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for the organophosphate insecticide chlorpyrifos in rats and humans. Toxicol Sci. 2002; 66(1): 34-53.
Worek F, Koller M, Thiermann H, et al.: Diagnostic aspects of organophosphate poisoning. Toxicology. 2005; 214(3): 182-189.
Ashani Y, Pistinner S: Estimation of the upper limit of human butyrylcholinesterase dose required for protection against organophosphates toxicity: A mathematically based toxicokinetic model. Toxicol Sci. 2004; 77(2): 358-367.
Gentry PR, Hack CE, Haber L, et al.: An approach for the quantitative consideration of genetic polymorphism data in chemical risk assessment: Examples with warfarin and parathion. Toxicol Sci. 2002; 70(1): 120-139.
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