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Contingency Medical Countermeasures for Mass Nerve-Agent Exposure: Use of Pharmaceutical Alternatives to Community Stockpiled Antidotes

  • Michael D. Schwartz (a1), Mark E. Sutter (a1) (a2), Derek Eisnor (a3) and Mark A. Kirk (a1)
Abstract

Having sufficient medical countermeasures (MCMs) available for the treatment of acetylcholinesterase-inhibiting nerve agent poisoned patients following a mass chemical exposure is a challenge for communities. After stockpiles containing auto-injectors are exhausted, communities need to be aware of alternative pharmaceutical options. The Department of Homeland Security Chemical Defense Program convened a federal interagency working group consisting of first responders, clinicians, and experts from the fields of medical toxicology, pharmacology, and emergency management. A literature review of pharmaceutical alternatives for treating nerve agent toxicity was performed. Pharmaceuticals that met the federal Public Health Emergency Medical Countermeasures Enterprise Product Specific Requirements were prioritized. Food and Drug Administration approval for one indication, market availability, and alignment to government procurement strategy were considered. This article summarizes the literature on comparative pharmacokinetics and efficacy against nerve agents (where available) of Food and Drug Administration approved drugs with muscarinic acetylcholine receptor antagonist and gamma-aminobutyric acid receptor agonist effects. This work is intended to serve as a resource of pharmaceutical options that may be available to communities (ie, emergency managers, planners, clinicians, and poison centers) when faced with a mass human exposure to a nerve agent and inadequate supplies of MCMs. (Disaster Med Public Health Preparedness. 2018;page 1 of 8)

Copyright
Corresponding author
Correspondence and reprint requests to Dr Michael D. Schwartz, Chemical Defense Program/Countering Weapons of Mass Destruction/Department of Homeland Security, 245 Murray Lane SW, Mailstop 0315, Washington, DC 20258 (Michael.schwartz@hq.dhs.gov).
References
Hide All
1. Eddleston, M , Buckley, NA , Eyer, P , Dawson, AH . Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607.
2. Zwiener, RJ , Ginsburg, CM . Organophosphate and carbamate poisoning in infants and children. Pediatrics. 1988;81(1):121-126.
3. Tokuda, Y , Kikuchi, M , Takahashi, O , Stein, GH . Prehospital management of sarin nerve gas terrorism in urban settings: 10 years of progress after the Tokyo subway sarin attack. Resuscitation. 2006;68(2):193-202.
4. United States Army Medical Research Institute of Chemical Defense (USAMRICD). Nerve agents. In: Medical Management of Chemical Casualties. 5th Edition. Published by the Office of the Surgeon General. 2014. 65–88.
5. Hall, AH , Walter, FG . Antidotes in general. In: Advanced HAZMAT Life Support. 3rd Edition. Tucson: FG Walter. 2003. 117-125.
6. Walter, FG . Toxidromes and toxicodynamics. In: Advanced HAZMAT Life Support. 3rd Edition. Tucson: FG Walter. 2003. 87-117.
7. National Library of Medicine. Chemical hazards emergency medical management. https://chemm.nlm.nih.gov/na_prehospital_mmg.htm#top. Accessed December 7, 2017.
8. United States Army Medical Research Institute of Chemical Defense (USAMRICD). “Medical Aspects of Chemical and Biological Warfare,” Volume 3, Table 5.7. Textbook of Military Medicine. April 1, 2000.
9. Thomas, RG . Chemoterrorism: nerve agents. In: Advanced HAZMAT Life Support. 3rd Edition. Tucson: FG Walter. 2003. 295-314.
10. Fraunfelder, FT . Ocular beta-blockers and systemic effects. Arch Intern Med. 1986;146(6):1073-1074.
11. Kaila, T , Korte, JM , Saari, KM . Systemic bioavailability of ocularly applied 1% atropine eyedrops. Acta Ophthalmol Scand. 1999;77(2):193-196.
12. Shiuey, Y1 , Eisenberg, MJ . Cardiovascular effects of commonly used ophthalmic medications. Clin Cardiol. 1996;19(1):5-8.
13. Corrigan, M , Wilson, SS , Hampton, J . Safety and efficacy of intranasally administered medications in the emergency department and prehospital settings. Am J Health Syst Pharm. 2015;72(18):1544-1554.
14. Rajpal, S , Ali R, Bhatnagar A, Bhandari SK, Mittal G. Clinical and bioavailability studies of sublingually administered atropine sulfate. Am J Emer Med. 2010;28:143–150.
15. Norderyd, J , Graf, J , Marcusson, A , et al. Sublingual administration of atropine eyedrops in children with excessive drooling – a pilot study. Int J Paed Dentist. 2017;27:22-29.
16. Comley, C , Galletly, C , Ash, D . Use of atropine eyedrops for clozapine-induced hypersalivation. Aust N Z J Psych. 2000;34(6):1033-1034.
17. Rajpal S, Mittal G, Sachdeva R, et al. Development of atropine sulphate nasal drops and its pharmacokinetic safety evaluation in healthy human volunteers. Env Toxicol Pharmacol. 2009;27:206–211.
18. Moylan-Jones, RJ , Thomas, DP . Cyclopentolate in treatment of sarin miosis. Br J Pharmacol. 1973;48:309-313.
19. Kato, T , Hamanaka, T . Ocular signs and symptoms caused by exposure to sarin gas. Am J Ophthalmol. 1996;121(2):209-210.
20. Bryant, SM , Rhee, JW , Thompson, TM , Aks, SE . Pretreating rats with parenteral ophthalmic antimuscarinic agents decreases mortality from lethal organophosphate poisoning. Acad Emerg Med. 2007;14:370-372.
21. Bryant, SM , Rhee, JW , Thompson, TM , et al. Parenteral ophthalmic tropicamide or cyclopentolate protects rats from lethal organophosphate poisoning. Am J Therap. 2009;16:231-234.
22. Mirakur, RK , Jones, CJ , Dundee, JW . Effects of intravenous administration of glycopyrrolate and atropine in anesthetized patients. Anesthesia. 1980;35:277-281.
23. Gomez, A , Bellido, I , Sanchez, de la Cuesta, F . Atropine and glycopyrronium show similar binding patterns to M2 (cardiac) and M3 (submandibular gland) muscarinic receptor subtypes in the rat. Br J Anesth. 1995;74(5):549-552.
24. Robenshtok, E , Luria, S , Tashema, Z , Hourvitz, A . Adverse reactions to atropine and the treatment of organophosphate intoxication. IMAJ. 2002;4:535-539.
25. Bardin, PG , Van Eeden, SF . Organophosphate poisoning: grading the severity and comparing treatment between atropine and glycopyrrolate. Crit Care Med. 1990;18(9):956-960.
26. Arendse, R1 , Irusen, E . An atropine and glycopyrrolate combination reduces mortality in organophosphate poisoning. Hum Exp Toxicol. 2009;28(11):715-720.
27. Ali-Melkkila, T , Kaila, T , Kanto, J . Glycopyrrolate: pharmacokinetics and some pharmacodynamic findings. Acta Anaesthesiol Scand. 1989;33:513-517.
28. Kaila, T , Ali-Melkkila, T , Lisalo, E , Kanto, J . Radioceptor assay for pharmacokinetic studies of glycopyrrolate. Pharmacol Toxicol. 1990;67:313-316.
29. Huang, F , Buchwald, P , Browne, CE , et al. Receptor binding studies of soft anticholinergic agents. AAPS Pharm Sci. 2001;3(4):1-13.
30. Roxane Laboratories Inc. Propantheline bromide: package insert and label information. 2003. https://druginserts.com/lib/rx/meds/propantheline-bromide/. Accessed December 7, 2017.
31. Roxane Laboratories Inc. Ipratropium bromide: package insert and label information. 2003. https://druginserts.com/lib/rx/meds/ipratropium-bromide-13/. Accessed December 7, 2017.
32. Perkins, MW , Wong, B , Rodriguez, A , et al. Inhalation toxicity of soman vapor in non-anesthetized rats: a preliminary assessment of inhaled bronchodilator or steroid therapy. Chem Biol Interact. 2013;206(3):452-461.
33. Barnes, PJ . The pharmacological properties of tiotropium. Chest. 2000;117(2 Suppl):63S-66S.
34. Wermeling, DP , Record, KA , Kelly, TH , et al. Pharmacokinetics and pharmacodynamics of a new intranasal midazolam formulation in healthy volunteers. Anesth Analg. 2006;103(2):344-349.
35. Bhattacharyya, M , Kalra, V , Gulati, S . Intranasal midazolam vs rectal diazepam in acute childhood seizures. Pediatr Neurol. 2006;34(5):355-359.
36. Silbergleit, R , Durkalski, V , Lowenstein, D , et al. NETT Investigators. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366(7):591-600.
37. McDonough, JH Jr , McMonagle, J , Copeland, T , et al. Comparative evaluation of benzodiazepines for control of soman-induced seizures. Arch Toxicol. 1999;73(8-9):473-478.
38. Graves, NM , Kriel, RL , Jones-Saete, C . Bioavailability of rectally administered lorazepam. Clin Neuropharmacol. 1987;10(6):555-559.
39. Wermeling, DP , Miller, JL , Archer, SM , et al. Bioavailability and pharmacokinetics of lorazepam after intranasal, intravenous, and intramuscular administration. J Clin Pharmacol. 2001;41(11):1225-1231.
40. McDonough, JH. Midazolam: an improved anticonvulsant treatment for nerve agent induced seizures. U.S. Army Medical Research Institute of Chemical Defense. Technical report: ADA409494; 2001.
41. Hung, OR , Dyck, JB , Varvel, J , et al. Comparative absorption kinetics of intramuscular midazolam and diazepam. Can J Anaesth. 1996;43(5 Pt 1): 450-455.
42. Divoll, M , Greenblatt, DJ , Ochs, HR , Shader, RI . Absolute bioavailability of oral and intramuscular diazepam: effects of age and sex. Anesth Analg. 1983;62(1):1-8.
43. Rey, E , Tréluyer, JM , Pons, G . Pharmacokinetic optimization of benzodiazepine therapy for acute seizures. Focus on delivery routes. Clin Pharmacokinet. 1999;36(6):409-424.
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Disaster Medicine and Public Health Preparedness
  • ISSN: 1935-7893
  • EISSN: 1938-744X
  • URL: /core/journals/disaster-medicine-and-public-health-preparedness
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