CHAPTER 63 - Prophylactic and Therapeutic Measures in Nerve Agent Poisoning

Abstract

This chapter focuses on the development of novel countermeasures against nerve agents to improve existing prophylactic and postexposure treatments. Nerve agents are regarded as the most toxic among all chemical weapons. Tabun was the first to be synthesized, followed by sarin and soman. VX is another type of nerve agent that was originally developed in the UK during research for new insecticides. The organophosphorus (OP) nerve agents are highly potent irreversible inhibitors of the enzyme acetylcholinesterase (AChE) that hydrolyzes acetylcholine (ACh). Accumulation of ACh in the synaptic cleft results in overstimulation of muscarinic and nicotinic receptors. This cholinergic overactivity can affect all organ systems. The toxic signs in humans include pinpoint pupils (miosis), bronchoconstriction, hypersalivation, increased lung secretions, sweating, diarrhea, loss of consciousness, seizures, and respiratory arrest. Miosis appears to be a very sensitive index of direct exposure, and can be painful for several days. Chest tightness, rhinorrhea, and increased salivation can occur within seconds/minutes of inhalation of nerve agents. If exposure is substantial, death may occur from respiratory arrest within minutes. Oximes should be used for treatment as soon as possible after exposure to nerve agent, because of the short time window of the aging process. Effective prophylactic treatment can be achieved by using a fixed dose of physostigmine in combination with varying doses of procyclidine. Increased lethal doses of soman can be counteracted by a corresponding increase in the procyclidine dose.