Medical Aspects of Chemical Warfare (2008) - The Black Vault

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Nerve AgentsChapter 5NERVE AGENTSFREDERICK R. SIDELL, MD*; Jonathan Newmark, MD † ; a n d John H. McDonough PhD ‡INTRODUCTIONHISTORYPHARMACOLOGY OF CHOLINESTERASE INHIBITORSEXPOSURE ROUTESEFFECTS ON ORGANS AND ORGAN SYSTEMSGENERAL TREATMENT PRINCIPLESSPECIFIC TREATMENT BY EXPOSURE CATEGORYRETURN TO DUTYTREATMENT GUIDELINES IN CHILDRENLESSONS FROM IRAN, JAPAN, AND IRAQPYRIDOSTIGMINE BROMIDE AS A PRETREATMENT FOR NERVE AGENTPOISONINGSUMMARY*Formerly, Chief, Chemical Casualty Care Office, and Director, Medical Management of Chemical Casualties Course, US Army Medical Research Instituteof Chemical Defense, Aberdeen Proving Ground, Maryland; deceased† Colonel, Medical Corps, US Army; Deputy Assistant Joint Program Executive Officer, Medical Systems, Joint Program Executive Office for Chemical/Biological Defense, Skyline #2, Suite 1609, 5203 Leesburg Pike, Falls Church, Virginia 22041; Adjunct Professor, Department of Neurology, F. EdwardHébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland‡ Major, Medical Service Corps, US Army (Retired); Research Psychologist, Pharmacology Branch, Research Division, US Army Medical Research Instituteof Chemical Defense, Room 161A, Building E-3100, 3100 Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010155
Medical Aspects of Chemical WarfareINTRODUCTIONNerve agents, secretly developed for military usebefore World War II, work by inhibiting cholinesterase(ChE). Though similar chemicals are used in areas suchas medicine, pharmacology, and agriculture, they lackthe potency of military agents, which are extremelytoxic. The military stockpiles of several major worldpowers are known to include nerve agents, and othercountries undoubtedly possess nerve agents as well.Terrorist organizations have used nerve agents to causemass injury and death, as was the case in the 1994 and1995 Aum Shinrikyo subway attacks in Japan. Othergroups, like Al-Qaeda, have indicated strong interestin obtaining these compounds. Therefore, it is imperativethat military medical personnel are familiar withthese agents, their effects, and the proper therapy fortreating casualties.HISTORYThe earliest recorded use of nerve agents comesfrom west Africa, where the Calabar bean, from theplant Physostigma venenosum, was used as an “ordealpoison” to combat witchcraft. Tribal members accusedof practicing witchcraft were forced to ingest the beansand if they survived, they were proclaimed innocent. 1,2An extract, “the elixir of the Calabar bean,” was laterused medicinally, 3 and in 1864, the active principle wasisolated by Jobst and Hesse and called physostigmine. 1Vee and Leven independently isolated this same substancein 1865 and named it eserine, 1 resulting in itsdual nomenclature.Five organophosphorus compounds are generallyregarded as nerve agents. They include tabun (NorthAtlantic Treaty Organization military designation GA),sarin (GB), soman (GD), cyclosarin (GF), and VX (nocommon name). More recently, a Soviet-developedsubstance closely related to VX, called VR or RussianVX, has been added to the list. The agents in the “G”series were allegedly given that code letter becausethey originated in Germany; the “V” in the latter seriesallegedly stands for “venomous.” GF is an old agent,an analog of sarin, which was previously discountedby the United States as being of no interest. During thePersian Gulf War, it was believed that Iraq might haveGF in its arsenal. The toxicity and speed of action of thisagent still merits consideration of it as a threat.The first organophosphorus ChE inhibitor wasprobably tetraethyl pyrophosphate, synthesized byWurtz and tasted (with no ill results) by Clermontin 1854. 4 During the next 80 years, chemists such asMichaelis, Arbusow, and Nylen made advances inorganophosphorus chemistry, but they did not realizethe toxicity of the substances with which they wereworking. 4In the early 1930s, interest in both physostigminetype(reversible) and organophosphorus-type (irreversible)ChE inhibitors increased. (The terms “reversible”and “irreversible” refer to the duration of binding ofthe compound with the enzyme ChE; see below.) Thereversible type, most of which are carbamates, weredeveloped for treating conditions such as intestinalatony, myasthenia gravis (a disorder in which theimmune system attacks postsynaptic acetylcholine[ACh] receptors), and glaucoma; for example, thereis a documented case from 1931 of a doctor treatinggastric atony with neostigmine. 1Lange and Krueger reported on the marked potencyof organophosphorus compounds in 1932 after notingthe effects of the vapors of dimethyl and diethyl phosphorofluoridateon themselves. 1,4 Shortly thereafter,the German company IG Farbenindustrie developedan interest in using organophosphorus compounds asinsecticides. On December 23, 1936, Gerhard Schrader,who headed the company ’ s research effort, synthesizedwhat is known today as tabun. 5,6 Like Lange and Krueger,he noted the toxicity (miosis and discomfort) ofthe vapors of the substance in himself.Over a year later, Schrader synthesized a secondorganophosphorus compound and named it sarin inhonor of those who were instrumental in its developmentand production: Schrader, Ambros, Rudriger,and van der Linde. 5 Because the German Ministry ofDefense required that substances passing certain toxicitytests be submitted to the government for furtherinvestigation, these compounds were examined forpossible military use.The potential of tabun and sarin as weapons wassoon realized. A large production facility was built inDyhernfurth, Poland (part of Germany at the time),and production of tabun began in 1942. 5,6 Sarin wasalso produced in Dyhernfurth and possibly at anotherplant in Falkenhagen. 6 Late in World War II, Soviettroops captured the Dyhernfurth facility, dismantledit, and moved it, along with key personnel, to theformer Soviet Union, where production of the agentscommenced in 1946. 6 Some believe the Soviets insistedon placing the border between Poland and Germanyas far west as the Oder-Neisse line, where it remainstoday, because Stalin did not want the Dyhernfurthsite, located between the Oder and Neisse rivers, tobe in Germany. 7156
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The Coat of Arms1818Medical Departm
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Textbooks of Military MedicinePubli
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MEDICAL ASPECTS o fCHEMICAL WARFARE
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ContentsContributorsForeword by The
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ContributorsMICHAEL ADLER, PhDResea
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DONALD M. MAXWELL, MSResearch Chemi
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ForewordThe US military has been co
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PrefaceA significant concern for th
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PrologueThe original edition of Med
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Page 180 and 181: Nerve AgentsAbout 10,000 to 30,000
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Nerve Agentstivity of smooth muscle
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Nerve Agents38. Grob D, Lilienthal
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Nerve Agents77. McDonough JH, Shih
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Nerve Agents117. McLeod CG Jr, Sing
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Nerve Agents154. Tryphonas l, Veino
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Nerve Agents193. Funckes AJ. Treatm
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Nerve Agents235. Suzuki T, Morita H
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Nerve Agents274. Pellegrini JE, Bak
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PROCESSMedical Aspects of Chemical
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Triage of Chemical CasualtiesChapte
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Triage of Chemical Casualtiesreceiv
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Triage of Chemical Casualtiescatego
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Triage of Chemical CasualtiesIn a f
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Triage of Chemical Casualtiesnose)
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Triage of Chemical CasualtiesWith n
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Triage of Chemical Casualties14. Sa
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Decontamination of Chemical Casualt
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• Analyze using GC-MS with methan
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Abbreviations and AcronymsAbBreviat
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Abbreviations and AcronymsPADPRP: p
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