Hakan PARLAKPİNAR, Seyhan POLAT, Mehmet GUNATA

Chemical warfare agents and treatment strategies

Chemical agents; is the general name of substances known to have toxic effects on the environment, which cause a large number of deaths and disabilities in a short period of time. These agents are divided into subclasses such as blister, nerve, choking, incapacitating/behavior altering, and asphyxiants/blood agents. In addition to the short-term effects of these agents there may be long-term reflections which affect the next generation. The previous century has been an important period in terms of observing the problems arising from the usage of the agents during wars. Deaths only due to nerve agents are thought to exceed 5 millions in recent wars. Especially the situation that the World War II has emerged shows the magnitude of the use of chemical agents. Due to these detrimental effects, their usage is restricted or prohibited by various international organizations. Despite these obstacles, chemical agents have been used by some countries and terrorist groups. Effects of these agents can take part vary from basic symptoms such as nose irritation to serious problems such as respiratory arrest. Healthcare professionals working in the management of exposure to these agents should have sufficient knowledge and be aware of their effects on the body. For this purpose; we discussed the serious effects of chemical warfare agents on human health and environment, post-exposure applications and pharmacological treatment options.

PDF

___

Syria’s latest atrocity: Assad kills at least 85 with chemical weapons https://www.economist.com/middle-east-and-africa/2017/04/08/assad-kills-at-least-85-with-chemical-weapons. access date 08.10.2018
Chauhan S, Chauhan S, D’Cruz R, et al. Chemical warfare agents. Environ Toxicol and Pharmacol 2008;26:113-22.
D’Agostino P. Chemical warfare agents. In: Bogusz MJ, ed. Forensic Science Handbook of Analytical Separations. 2 nd edition. Alberta: Elsevier BV; 2008. p. 839-72.WHO concerned about suspected chemical attacks in Syria. http://www.who.int/news-room/detail/11-04-2018-who-concerned-about-suspected-chemical-attacks-in-syria access date 08.4.2018
Syria attack: Chemical weapons inspectors retrieve samples from Douma. https://www.independent.co.uk/news/world/middle-east/syria-douma-chemical-weapons-attack-latest-eastern-ghouta-russia-assad-a8315746.html access date 08.4.2018
Schwenk M. Chemical warfare agents. Classes and targets. Toxicol Lett 2018;293:253-63.
Bessac BF, Jordt SE. Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiology (Bethesda) 2008;23:360-70.
Paromov V, Suntres Z, Smith M, et al. Sulfur mustard toxicity following dermal exposure: role of oxidative stress, and antioxidant therapy. J Burns Wounds 2007;7:60-85.
Li C, Srivastava RK, Weng Z, et al. Molecular mechanism underlying pathogenesis of lewisite-induced cutaneous blistering and inflammation: chemical chaperones as potential novel antidotes. Am J Pathol 2016;186:2637-49.
Centers for Disease Control and Prevention (CDC)-Emergency Response Safety and Health Database: Blister Agent: LEWISITE (L), The National Institute for Occupational Safety and Health(NIOSH). https://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750006.html access date: 08.8. 2018
Eddleston M, Chowdhury FR. Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new. Br J Clin Pharmacol 2016;81:462-70.
Eddleston M, Buckley NA, Eyer P, et al. Management of acute organophosphorus pesticide poisoning. Lancet 2008;371:597-607.
Fraser TR. On the characters, actions, and therapeutic use of the ordeal bean of Calabar. Edinburgh Medical Journal 1863;9:36-56.
Bennion BJ, Essiz SG, Lau EY, et al. A wrench in the works of human acetylcholinesterase: soman induced conformational changes revealed by molecular dynamics simulations. PLoS One 2015;10(4): e0121092.
Wiener SW, Hoffman RS. Nerve agents: Acomprehensive review. J Intensive Care Med 2004;19:22-37.
rabetz H, Thiermann H, Felgenhauer N, et al. Organophosphate poisoning in the developed world-a single centre experience from here to the millennium. Chem Biol Interact 2013;206:561-8.
Wajner JE 3 rd, Lung D. Case files of the University of California San Francisco Medical Toxicology Fellowship: Acute chlorine gas inhalation and the utility of nebulized sodium bicarbonate. J Med Toxicol 2013;9:259-65.
Nodelman V, Utman JS. Longitudinal distribution of chlorine distribution in human airways: comparison of nasal and oral quiet breathing. J Appl Physiol 1999;86:1984-93.
Barrow CS, Alarie Y, Warrick JC, Comparison of the sensory irritation response in mice to chlorine and hydrogen chloride. Arch Environ Health 1977;32:68-76.
McNulty MJ, Chang JCF, Barrow CS, et al. Sulfhydryl oxidation in rat nasal mucosal tissues after chlorine inhalation. Toxicol Lett 1983;17:241-6.
Schraufstaetter IU, Browne K, Harris A, et al. Mechanisms of hypochlorite injury of target cells. J Clin Invest 1990;85:554-62.
Cevik Y, Onay M, Akmaz I, et al. Mass casualties from acute inhalation of chlorine gas. South Med J 2009;102:1209-13.
Bosse GM. Nebulized sodium bicarbonate in the treatment of chlorine gas inhalation. J Toxicol Clin Toxicol 1994;32:233-41. 23.Da R, Blanc PD. Chlorine gas exposure and the lung: a review. Toxicol Ind Health 1993;9:439-55.
Barret L, Faure J. Chlorine poisoning. Lancet 1984;1:561-2.
Moulick ND, Banavali S, Abhyankar AD, et al. Acute accidental exposure to chlorine fumes-a study of 82 cases. Indian J Chest Dis Allied Sci 1992;34:85-9.
Asauliuk IK. Symptoms of acute inhalation lesions caused by trichloronitromethane. Vrach Delo 1990;1:104-6.
Prudhomme JC, Bhatia R, Nutik JM, et al. Chest wall pain and possible rhabdomyolysis after chloropicrin exposure. A case series. J Occup Environ Med 1999.41:17-22.
Yamauchi T, Yamano Y, Yamanaka K, et al. Possible production of arsenic hemoglobin adducts via exposure to arsine. J Occupl Health 2015;57:161-8.
Pakulska D, Czerczak S. Hazardous effects of arsine: a short review. Int J Occup Med Environ Health 2006;19:36-44.
Kato K, Yamanaka K, Shimoda Y, et al. Arsine toxicity is induced by inhalation but not by percutaneous exposure in hairless mice. J Toxicol Sci 2014;39:301-10.
Rael LT, Ayala-Fierro F, Bar-Or R, et al. Interaction of arsine with hemoglobin in arsine-induced hemolysis. Toxicol Sci 2006;90:142-8.
WO 32/20163 Development of defensive chemical warfare capability with incapacitating agents 1962-1966. The operational use of chemical incapacitating agents by M.A.P.Hogg, CDEE Porton Down 29.081963.
Ozucelik DN, Karcioglu O, Topacoglu H, ark. Kimyasal savaş ajanları. Akademik Acil Tıp Dergisi 2005;3:28-32.
Byrns MC and Penning TM. Environmental Toxicology: Carcinogens and Heavy Metals. In: Brunton LL, editor-in-chief and Hilal-Dandan R, Knollmann BC, eds. Goodman&Gilman’s The Pharmacological Basis of Therapeutics. 13 th edition. San Diego; 2018. p. 1312.
Kosnett MJ. Heavy Metal Intoxication & Chelators. In: Katzung BG, ed. Basic & Clinical
Pharmacology. 14 th edition. San Francisco; 2018. p. 1030.
Brown JH, Brandl K, Wess J. Muscarinic Receptor Agonists and Antagonists. In: Brunton LL, editor-in-chief and Hilal-Dandan R, Knollmann BC, eds. Goodman&Gilman’s The Pharmacological Basis of Therapeutics. 13 th edition. San Diego; 2018. p. 149,153.
Huang YJ, Huang Y, Baldassarre H, et al. Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning. Proc Natl Acad Sci USA 2007;104:13603-8.
Kulig K. Cyanide antidotes and fire toxicology. N Engl J Med 1991;325:1801-2.
Evison D, Hinsley D, Rice P. Chemical weapons. BMJ 2002;324:332-5.