Being Prepared

Abstract

Nerve agents are extremely toxic and are some of the most lethal substances on earth. This group of chemicals consists of sarin, cyclosarin, soman, tabun, VX, and VR. It is currently unknown how many countries possess these chemicals and in what quantities. These agents work through altering the transmission and breakdown of acetylcholine by binding to, and inactivating, acetylcholinesterase. This results in an uncontrolled and overwhelming stimulation of both muscarinic and nicotinic receptors. Receptor activation at these sites can lead to a wide variety of clinical symptoms, with death frequently resulting from pulmonary edema. Antidotal therapy in this setting largely consists of atropine, pralidoxime, and benzodiazepines, all of which must be administered emergently to limit the progression of symptoms and prevent the enzyme inactivation from becoming permanent. This article reviews the mechanism of action of the nerve agents and their effects on the human body, the currently available therapies to mitigate their impact, and important therapeutic considerations for health care practitioners in the emergency department.

Inhibition of Soluble Epoxide Hydrolase as a Novel Approach to High Dose Diazepam Induced Hypotension

“…Occasionally, BZDs are used in relatively high doses such as antidotes for pesticide or nerve gas poisoning or following overdose. Thus, an antidote for BZDs becomes necessary to prevent lethality [5, 6]. In contrast to the availability of multiple BZD drugs the only FDA approved antidote for an overdose of BZDs is flumazenil.…”

Nerve agents: a guide for emergency nurses. Part 1

“…The group of nerve agents called Novichok was developed by the Russians between 1971 and 1993 and has five variants numbered one to five. All nerve agents are chemically related to organophosphate insecticides originally developed to protect crops (Bailey et al 2014). However, at the beginning of World War II the German military began to develop organophosphate-based nerve agents for military purposes (Barthold and Schier 2005).…”

“…Generally, nerve agents and organophosphate-based insecticides act by altering the effects of the neuro-transmitter acetylcholine (Sidell and Borak 1992). In the human nervous system acetylcholine regulates nicotinic and muscarinic receptors found in the central, sympathetic and parasympathetic nervous systems and in skeletal muscles (Bailey et al 2014). Normally neuro-transmission takes place when an action potential is conducted along a neuron to the distal portion of the telodendria called the axonal terminus where acetylcholine is released (Huether and McCance 2016).…”

“…Following contraction, acetylcholine detaches from the postsynaptic receptor, hydrolysed and then deactivated by acetylcholinesterase (Sidell and Borak 1992). Therefore, the consequences of blocking acetylcholinesterase are overpowering amounts of acetylcholine in the synaptic cleft (Bailey et al 2014). Classically nerve agents attach themselves at the active site of acetylcholinesterase thus blocking the deactivating function of acetylcholinesterase on acetylcholine.…”

“…Nerve agents are chemically related to organophosphate insecticides and are among the most toxic and lethal substances known to mankind (Bailey et al 2014). Therefore, early recognition is vital to manage affected patients safely and effectively and to assure the health and safety of healthcare staff (Candiotti 2017).…”