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Chemical weapons have been used since the Middle Ages, though it took industrial advancements in the 19th century to make their mass production and deployment possible.1 Chlorine, phosgene, sulfur mustard, and lewisite caused 100,000 deaths and 1.2 million casualties in World War I.2 Hydrogen cyanide was used in World War II.1 Agent Orange was used in the Vietnam War.1 Sarin was used in the Tokyo subway, causing 5,500 casualties and 12 deaths. An Iraqi nerve gas attack in Halabja killed 5,000 civilians.3

There are 70 different chemicals that can be used in chemical warfare which may elicit a common response.1 Multi-Threat Medical Countermeasure (MTMC) is based on the premise that the body’s response to any toxic chemical involves a common underlying biochemical signal pathway.4 MTMC drugs can target this common pathway and thus protect against various chemical agents. This pathway is the inflammatory pathway and involves proteases, inflammatory cytokines such as tumor necrosis factor (TNF), interleukin-1, interleukin-8, platelet activating factor, N-methyl-d-aspartate glutamate receptors, acethylcholine, substance P and poly (ADP-ribose) polymerase. However, there is still no specific drug to empirically treat any chemical attack; thus the approach would be specific to one chemical agent. Nerve agents, vesicants, psychomimetics, and riot controlling agents will be discussed here.


Nerve agents are a class of chemical warfare agents that act through the irreversible inhibition of acetylcholinesterase via phosphorylation at cholinergic and central nervous system (CNS) synapses (Table 29-1). This process leads to the accumulation of acetylcholine in the central and peripheral nervous systems, with a host of autonomic symptoms that may ultimately lead to death. Nerve agents are, for the most part, colorless and tasteless liquids with high volatility that easily transform into vapor and aerosol forms, hence the common term, “nerve gases.” Owing to their liposolubility and hydrosolubility, these agents are absorbed quickly through the eyes, skin, and respiratory tract.


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