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.
Toxicology
Anthony FT Brown, Michael D Cadogan in Emergency Medicine, 2020
Patients present with degrees of cholinergic crisis, usually within 4 h of ingestion or exposure. Specific manifestations include: Muscarinic:bronchorrhoea, bronchospasm, vomiting, pinpoint pupils, bradycardia and hypotensionexcessive sweating, lacrimation, salivation, profuse diarrhoea and urination.Nicotinic: fasciculation, tremor, weakness, muscle paralysis, tachycardia and hypertension.CNS: initial agitation followed by sedation and altered mental status leading to convulsions and coma.
Practice Paper 2: Answers
Anthony B. Starr, Hiruni Jayasena, David Capewell, Saran Shantikumar in Get ahead! Medicine, 2016
Myasthenia gravis is characterized by an inability to sustain a maintained or repeated contraction of striated muscle (fatigability). It is caused by autoimmune destruction of postsynaptic acetylcholine receptors (AChRs) in the neuromuscular junction. It is more common in women between 20 and 40 years of age. The first symptom may be diplopia or ptosis, and the cardinal feature is fatigability. Symptoms are worse after exercise and at the end of the day. Occasionally, a sudden weakness can occur (myasthenic or cholinergic crisis). Diagnosis of myasthenia gravis is by the Tensilon test: intravenous edrophonium bromide (a short-acting anticholinergic) is administered and, if the weakness transiently improves, myasthenia is confirmed. Anti-AChR antibodies are found in 80–90% (and have a sensitivity >90% and specificity of 99%). All patients with myasthenia gravis should have a chest CT scan to rule out thymoma. Management is with anticholinergics (e.g. pyridostigmine). An overdose of anticholinergics can cause a cholinergic crisis (leading to muscle fasciculation, paralysis, pallor, sweating, excessive salivation and small pupils). This may be distinguished from a myasthenia crisis (severe weakness due to exacerbation of myasthenia) by injection of edrophonium.
Efficacy of an organophosphorus hydrolase enzyme (OpdA) in human serum and minipig models of organophosphorus insecticide poisoning
Published in Clinical Toxicology, 2020
Michael Eddleston, R. Eddie Clutton, Matthew Taylor, Adrian Thompson, Franz Worek, Harald John, Horst Thiermann, Colin Scott
Organophosphorus (OP) insecticide poisoning kills over 200,000 people each year, mostly following self-harm, in rural Asia [1,2]. These compounds inhibit multiple enzymes, in particular, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) [3–5]. While BuChE inhibition appears unimportant in acute poisoning, AChE inhibition results in overstimulation of acetylcholine receptors in the autonomic nervous system, neuromuscular junction (NMJ), and central nervous system [3]. This syndrome is termed the cholinergic crisis and causes acute respiratory and cardiovascular failure. Self-poisoning is also complicated by the presence of large amounts of solvents which are themselves toxic [6]. Many deaths occur within hours of pesticide ingestion during the acute cholinergic crisis, usually due to acute respiratory failure that occurs before mechanical lung ventilation is instigated [7]. Other deaths occur later, in ventilated patients due to cardiovascular collapse [8], failure of NMJ transmission, or complications of aspiration [9,10].
Influence of experimental end point on the therapeutic efficacy of the antinicotinic compounds MB408, MB442 and MB444 in treating nerve agent poisoned mice – a comparison with oxime-based treatment
Published in Toxicology Mechanisms and Methods, 2020
Jiri Kassa, Christopher M. Timperley, Mike Bird, A. Christopher Green, John E. H. Tattersall
Organophosphorus nerve agents are considered the most dangerous chemical warfare agents. They exert their acute toxic effects mainly by irreversibly inhibiting acetylcholinesterase (AChE, EC 3.1.1.7) by phosphylation of its active site (serine hydroxyl group). Subsequent accumulation of the neurotramitter acetylcholine (ACh) in the central and peripheral nervous systems leads to overstimulation of muscarinic (mAChRs) and nicotinic acetylcholine receptors (nAChRs). Events over the last 5 years involving the confirmed use of nerve agents against individuals in the Syrian Arab Republic (Rice et al. 2015), in Malaysia and in the United Kingdom of Great Britain and Northern Ireland (OPCW (Organisation for the Prohibition of Chemical Weapons) Technical Secretariat 2018), have drawn attention internationally, including among scientists. These compounds cause a range of signs and symptoms collectively referred to as acute cholinergic crisis, indicated by muscle twitching and paralysis, lachrymation, miosis, salivation, respiratory failure, seizures and coma (Leibson and Lifshitz 2008). Death occurs due to acute central and peripheral respiratory failure resulting from bronchospasm, excessive bronchial secretion, paralysis of respiratory muscles, and depression of brain respiratory centers (Bajgar 2004; Colovic et al. 2013).
Treating organophosphates poisoning: management challenges and potential solutions
Published in Critical Reviews in Toxicology, 2020
Maria Alozi, Mutasem Rawas-Qalaji
Since ACh is an essential neurotransmitter involved in various chemical pathways (Brady et al. 2011) (Figure 4), a myriad of toxic effects can result from its accumulation in OP poisoned individuals. The first symptoms observed within the first few hours occur collectively as a part of the acute cholinergic crisis (ACC) and include salivation, lacrimation, emesis, miosis, bradycardia, hypotension, bronchoconstriction, and convulsions (Peter et al. 2014). These signs may be followed by an intermediate syndrome (IMS) phase, which typically occurs within 24–96 h in 10–40% of affected individuals and is characterized by muscle weakness, respiratory insufficiency, and decreased deep tendon reflexes. If appropriate therapy is provided, recovery from IMS may occur within 5–18 days (Bird 2020). Unfortunately, some patients can also develop painful paresthesias and even permanent disabilities during the OP-induced delayed neuropathy (OPIDN) phase, which typically occurs within 1–3 weeks after ingesting certain types of OP, such as chlorpyrifos (Bird 2020).