Nerve Agents

G-Series• First groups of nerve agents, the G-series, developed in

Germany in 1936 by Dr. Schrader• Schrader’s group working to develop new insecticides for IG

Farben• Developed the nerve agent Tabun; 5 ppm killed all insects

dosed (1 ppm = 1 mg/L)• Schrader and coworker exposed when a drop of Tabun spilled

on lab bench. Within minutes, they experienced miosis, dizziness, shortness of breath. Recovery took 3 weeks.

• In 1935, Nazi government law required all inventions of military significance to be reported to Military of War; Tabun given code name Le-100 and Trilon-83

G-Series• Schrader’s group discovered Sarin in 1938• Given code name T-144 or Trilon-46• Sarin was 10x more potent than Tabun• Soman discovered in 1944 by Dr. Kuhn in 1944• Cyclosarin discovered during WWII.• The G-series name created by United States when it

uncovered the German research, labeling Tabun as GA (German Agent A), Sarin as GB, Soman as GD, Ethyl sarin as GE, and cyclosarin called GF.

• Ct = product of concentration (C) of a vapor or aerosol to which one is exposed and the time (t) over which one is exposed to the concentration (C).• LCt50 = the Ct of an agent that will be lethal (L) to half of the

population exposed to it• ICt50 = the Ct that will incapacitate (I) half of the population

exposed to it• MCt50 = estimated Ct that will cause miosis (pinpointing of the

pupils)

• The LD50 of VX, when placed on human skin, is the size of a droplet that will cover the width of 2 columns of the Lincoln Memorial on a Lincoln penny.

Mechanism of Action• Blocks acetylcholinestarase (AChE)• AChE is found in many different types of conducting tissue:

nerve and muscle, central and peripheral tissues, motor and sensory fibers, and cholinergic and noncholinergic fibers; also found on red blood cell membranes

• Normal function of AChE is to break down acetylcholine, which is a neurotransmitter in the nervous system. Under normal conditions, when the signaled action at each step is completed, acetylcholine is broken down by AChE, stopping the action.

• If AChE is inhibited, acetylcholine continues to accumulate, and the nerves continue to send signals, or continue to fire. As the nerve continues to fire, the muscles and organs become hyperactive and twitch uncontrollably, and glands secrete copiously

Organophosphates & Carbamates - excess acetylcholine

The parts of the body affected by excessive acetylcholine accumulation:

• Eyes• Nose (glands)• Mouth (glands)• Respiratory tract• Gastrointestinal tract• Cardiac muscle• Sweat glands• Skeletal muscle• Central nervous system

Eyes• Affected by direct contact with nerve agent; if route is through

skin or ingestion, effect on eyes is delayed or may not occur• Main effect: miosis, or pinpointing, of the pupils• One or both pupils my be pinpointed and unresponsive to light

or dark• Miosis causes a complaint of dim vision that is more

pronounced in dim conditions• Frontal headache, mild aching around eye, or severe pains are

common complaints of people exposed to moderate amounts• Twitching of eyelids may occur, eyes may be reddened

Nose• Secretory glands of nose and mouth are senstive• When poisoning occurs dermally or by ingestion, nose will be

affected, but only in response to systemic (whole body) involvement.

• Nose will begin to run; “like a leaky faucet”• Mouth will secrete such excessive amounts of saliva that

watery secretions run out the corners of the mouth

Respiratory tract• Inhalation of small amount will cause person to complain of

tightness in the chest or shortness of breath (dyspnea);• This occurs because acetylcholine simulates the muscle in the

airways to contract and constrict the airways (bronchoconstriction)

• As concentration increases, breathing difficulty will become more severe

• One or two breaths of high concentration will cause gasping and irregular respiration within seconds to a minute or two

• Cessation of breathing can occur within minutes after exposure to large amount of vapor

• Excessive bronchial secretions caused by stimulation of airway glands make breathing difficulties worse

Gastrointestinal (GI) tract• After exposure to large but sublethal exposure, person will

complain of nausea and may vomit• Nausea and vomiting by be first effects from liquid nerve

agent on skin • Person may belch and have diarrhea or involuntary defecation

and urinaiton• Usually occur within several minutes of vapor exposure• After dermal exposure to liquid, the effects may not begin for

as long as 18 hours after exposure

Cardiac• Heart rate my increase or decrease after exposure• Blood pressure usually increases

Sweat glands• When skin penetration occurs after liquid or vapor exposure,

localized sweating occurs and progressively spreads over the surrounding skin area

Skeletal muscles• After exposure to moderate or large amount or nerve agent,

person will complain of weakness and twitching of muscle groups

• Twitching can first be noticed at the site of the liquid drop on skin

• Muscles may shoe a rippling effect (fasciculations)• http://vimeo.com/36476690• As effects progress, muscles can go into prolonged

contractions; large muscle groups may begin unsynchronized contractions that cause arms and legs to flail about; hyperactivity of muscles may lead to muscle fatigue and flaccid paralysis (limp, unable to move)

Central nervous system (CNS)• When large inhalation doses or liquid exposures occur, effects

are rapid and usually fatal. • Person almost immediately loses consciousness, followed by

seizures• Several minutes later, respiration ceases

• https://www.youtube.com/watch?v=mkbBnvz0rw0