Military Chemical Casualty Treatment
Brian J. Lukey, James A. Romano, Salem Harry in Chemical Warfare Agents, 2019
Nerve agents are the most toxic of the known chemical agents. They are hazards in their liquid, aerosol, and vapor states and can cause death within minutes after exposure. Nerve agents inhibit the enzyme acetylcholinesterase in tissue and blood, and their effects are caused by the resulting excess of acetylcholine, a neurotransmitter, in tissue. This creates what is called a “cholinergic crisis.” Organs with cholinergic receptor sites include the smooth muscles, skeletal muscles, central nervous system (CNS), and most exocrine glands (sweat, tears, saliva, and mucosal secretions). In addition, cranial efferents and ganglionic afferents are cholinergic nerves. Exposure to a small amount of nerve agent vapor causes effects in the eyes, nose, and airways. These effects are from local contact of the vapor with the organ and do not alone indicate systemic absorption of the agent. In this circumstance, the circulating erythrocyte-cholinesterase may be depressed and used as a possible indicator of exposure. A very small amount (usually non-lethal) of liquid agent on the skin causes systemic effects initially in the gastrointestinal (GI) tract. Localized sweating and muscle fasciculations may be seen at the spot. Lethal amounts of vapor (almost immediate) or liquid (once absorption takes place) cause a rapid cascade of events culminating within a minute or two in loss of consciousness and convulsive activity, followed by apnea (breathing cessation) and muscular flaccidity within several more minutes.
Battlefield Chemical Inhalation Injury
Jacob Loke in Pathophysiology and Treatment of Inhalation Injuries, 2020
Chemical warfare continued to be of both theoretical and practical interest in the years after World War I. By 1923 a joint German-Soviet company was formed for the development and manufacture of chemical agents. In 1929 the Japanese began chemical warfare research and development activities and subsequently produced substantial quantities of a variety of poison gases, mustard gases among them. Because of the secrecy surrounding such manufacture, gasproduction employees were often not well informed or protected in their work environment. The neoplastic hazard of long-term/multiple exposures to mustard was thereby identified. Mustard gases were apparently used by the Japanese in their military encounters with the Chinese in the late 1930s and by the Italians in Ethopia in 1936. Mustards and a variety of other agents were prepared and stockpiled in strategic locations by the allies during World War II. The Germans, meanwhile, had developed and stockpiled a new group of toxic gases, the organophosphates. Because of the neurologic toxicity of the organophosphates, they came to be known as “nerve agents.” Neither the Allies or the Germans, for reasons that remain unclear, used chemical agents in any military campaign during World War II.
Biomarkers of Chemical Warfare Agents
Anthony P. DeCaprio in Toxicologic Biomarkers, 2006
The predominant nerve agents of historical note are the “G-agents” (GA-tabun, GB-sarin, GD-soman, GF-cyclo-sarin) and the “V-agents” (VX and, more recently, VR). Many of these nerve agents are related to common pesticides and function through inhibition of the enzyme acetylcholinesterase (AChE). AChE is a critical regulatory enzyme in the conduction of neuromuscular activity in that it breaks down the neurotransmitter acetylcholine (ACh). When the nerve agent binds to the active site of AChE, the enzyme can no longer function in destroying ACh. As ACh builds up in the neuromuscular junction, it causes continual nerve impulse generation and organ stimulation. Organs with cholinergic receptors include smooth muscle, skeletal muscle, central nervous system, and exocrine glands. The effects of nerve agent exposure vary based on dose and route of exposure but can range from miosis through increased secretions, bronchoconstriction, muscle fasciculations, to convulsions, seizures, loss of consciousness, and death at the higher exposures.
Evaluating mice lacking serum carboxylesterase as a behavioral model for nerve agent intoxication
Published in Toxicology Mechanisms and Methods, 2018
Emily N. Dunn, Teresa M. Ferrara-Bowens, Mark E. Chachich, Cary L. Honnold, Cristin C. Rothwell, Heidi M. Hoard-Fruchey, Catherine A. Lesyna, Erik A. Johnson, Douglas M. Cerasoli, John H. McDonough, C. Linn Cadieux
Nerve agents are organophosphorus compounds that inhibit the enzyme acetylcholinesterase (AChE) and cause various peripheral and central nervous system (CNS) effects, such as miosis, rhinorrhea, respiratory distress, fasciculations, convulsions, and/or seizures (Ohbu et al. 1997; Wiener and Hoffman 2004). Within 2 min of exposure to the nerve agent soman (GD), inhibition of AChE by this compound cannot be reversed (Svensson et al. 2005). GD-induced seizure activity in mice typically begins with mastication followed by head tremors that progress in intensity to become full-body convulsions that often correlate with electrographic seizure onset (McDonough and Shih 1993). The duration of these unremitting seizures, known as status epilepticus (SE), is linked with brain damage (Carpentier et al. 2000) that results in various behavioral deficits (Raffaele et al. 1987; Filliat et al. 2007).
Anticonvulsant effectiveness of scopolamine against soman-induced seizures in African green monkeys
Published in Drug and Chemical Toxicology, 2022
John H. McDonough, Joseph D. McMonagle, Benedict R. Capacio
Nerve agents are highly toxic organophosphate compounds. They exert their toxic effects by inhibiting the cholinesterase (ChE) family of enzymes to include acetylcholinesterase (AChE), the enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh). Nerve agents bind to the active site of the AChE enzyme, thus preventing it from hydrolyzing ACh. ACh is the neurotransmitter at the neuromuscular junction of skeletal muscle, the preganglionic nerves of the autonomic nervous system, and the postganglionic parasympathetic nerves, as well as muscarinic and nicotinic cholinergic synapses within the central nervous system (CNS). Following nerve agent exposure and the inhibition of the AChE enzyme, levels of ACh rapidly increase at the various effector sites, resulting in continuous overstimulation. This hyperstimulation of the cholinergic system at central and peripheral sites leads to the toxic signs of poisoning with these compounds. The signs of poisoning include miosis (constriction of the pupils), increased tracheobronchial secretions, bronchial constriction, laryngospasm, increased sweating, urinary and fecal incontinence, muscle fasciculations, tremor, convulsions/seizures of CNS origin, and loss of respiratory drive from the CNS (Departments of the Army, Navy, Air Force, and Commandant Marine Corps 1995, Aas 2003, Chemical Casualty Care Division 2014).
The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant
Published in Cutaneous and Ocular Toxicology, 2018
Christopher Dalton, Charlotte Hall, Helen Lydon, John Jenner, J. Kevin Chipman, John S. Graham, Robert P. Chilcott
Application of GD to damaged skin in vivo resulted in the rapid onset of multiple observable (Table 1) or physiological (Table 2) signs of nerve agent poisoning. In addition, only one of the animals in the GD-exposed untreated group survived to six hours post-exposure (Figure 1) and median survival time differed significantly between the control and GD-exposed untreated groups (Figure 2). Two animals in the GD-exposed WoundStat™-treated group survived until the end of the study period (Figure 1). Signs of nerve agent poisoning were also observed in these animals, although there tended to be a longer latency in the onset of signs when compared to the untreated group (Table 1). In addition, there was no significant difference in median survival time between the GD-exposed WoundStat™-treated group and the unexposed control group (Figure 2). All six animals in the control group survived the six-hour study duration and showed no sign of GD intoxication.