the dose is several orders of magnitude lower than a fatal
dose.

Far pharmacologic purposes, chemical agents may be
classified according to their effect on the body. Some of
these classes are nerve agents, vesicants, irritants, and
systemic poisons. The important members of each class
will be discussed.

NERVE AGENTS

The anticholinesterase agents have been discussed in
detail in Chap. 31. The compounds that are potential
chemical agents are a group of highly toxic erganic
esters of phosphoric acid derivatives which have phar-
macologic effects resembling those of physostigmine,
The principal differences are that (1) they are among the
most toxic of all chemicals, being one to several orders
of magnitude more toxic than commonly used pesticides
and insecticides and (2) they have more potent and
(Prolonged effects, due in Part to the degree to which
they irreversibly inhibit both plasma and red blood cell
cholinesterase. Tabun, or dimethylamidoethoxyphos-
phoryl cyanid [(CH3),N—P(OKCN)--OC.Hs ] (GAi, was
manufactured by the Germans during the Second World
War on a large scale. The development of sarin, or

isopropyl methylphosphonofluoridate {CH —P(O)F}—
OCH(CH;).] (GB), was begun in Germany during the
latter part of the Second World War (cf. Table 31-5).

A number of related but somewhat fess toxic com-
pounds have been used throughout the world as insec-
ticides, and their use has resulted in numerous instances
of poisoning, some fatal.

Parathion, TEPP, and

Malathion are commen examples of such compounds-.

now in use. More recently certain carbamaites, also
cholinesterase inhibitors, represented by such trade
names as Carbaryl and Sevin, are being used exten-
sively. The symptoms and treatment of poisoning by
these compounds are similar to those of the neve agents
(cf. Chap. 61),

The nesve agents are nearly colorless and essentially
odorless liquids, varying in volatility at Ordinary room
temperatures. In toxic amounts, aqueous solutions are
tasteless. Most of these compounds react slowly with
water and rapidly with strong alkali, yielding hydrolysis
products which are usually either nontoxic or less toxic
than the original compound. They range in persistency
from those with high volatility to those of low volatility
with high persistence.

The anticholinesterases may be absorbed across any
cell barrier, When dispersed as vapors or aerosols, they
are readily absorbed through the respiratory tractor the
eyes. resulting in local effects on these issues. Liquid
nene agents may be absorbed through the shin, When-

Chemicals Used as Weasons in War

ever absorption of sufficient chemical occurs by any
route, the result is a generalized systemic effect,
Symptoms begin promptly and Progress rapidly. The
sequence of signs and symptoms varies with the route of
exposure, Whereas respiratory symptoms are usually
the first to appear after inhalation of vapor or serocnl,
gastrointestinal symptoms usually appear first
ingestion of solutions containing nerve agents. Simi-
larly, focatized sweating and muscle fasciculation are
usually the first signs observed after cutaneous expeyjure,
If eye exposure has not occurred by liquid droplet or
vapor, the ocular manifestations of miosis may be atsent
or mild until severe systemic intoxication has taken
place,

Mechanism of Action

The effects of the neve agents are due largely to their
ability to inhibit cholinesterases throughout the bedy.
Since the rormal function of these enzymes is to hydro-
lyze acetytcholine wherever this compound is released,
such inhibition results in the accumulation of excessive
concentrations of acetylcholine at its various sites of
action. The accumulation of excess acetylcholine pro-
duces nausea, vomiting, abdominal cramps, diarrhea,
sweating, increased bronchial and salivary secretions,
and bradycardia. \When the accumulation occurs near
the ends of the motor nerves to skeletal muscles,
the resulting action is first that of stimulation as in
muscular fasciculation, followed by muscle weakness,
and finally flaccid paralysis. Finally, the accumulation
of excessive concentrations of acetyicholine in the
brain and spinal cord is thought to be responsible for
the described signs and symptoms referable to the cen-
tral nervous system. It would be useiul tor the average
medical reader simply to remember that the signs and
symptoms of anticholinesterase intoxication appear to
be very similar to Overstimulation of the Paras, mpa-
thetic nervous system.

fOany such com

Te effector repeated exposures is cumulative.
Smee OE EPEAT CARO en EU
Sometimes We see Taboratory and enginesrring personnel
who, through unsuspected repented soma!l exposures,
have very fow circulating Cholinesterase activity and are
asymptonaaue ercept for increased Nitigue and minor
subjective complaints. The degre of exposure reguiced
to produce: severe sy mptams in wor hers in this abourmal

state is not known, but itis belie, ect to be less than half

SOTA =. Ane en tea tee,