sarin - tokyo incident 
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 sarin - tokyo incident

My wife has been exposed to sarin, in the incident in Tokyo this monday.
Does anyone know anything about this drug? Or where I might find information?
How it might affect a fetus? Information is a little hard to come by in Japan.
She seems to be recovering well, but I am worried about long-term consequences.


Sat, 06 Sep 1997 21:47:16 GMT
 sarin - tokyo incident
Sarin chemical name is: isopropyl methylphosphonofluoridate.
is a nerve poison sim. to diisopropyl fluorophosphate and tetraethyl
pyrophosphate.
a very potent irreversible cholinesterase inhibitor.  it is a more toxic
nerve gas than "tabun" or "soman".  Cholinesterase one of a family of
enzymes capable of catalyzing the hydrolysis of acylcholines within the
central nervous system and at peripheral neuro-effector junctions (ex.
motor endplates and autonomic ganglia). There is no listing of sarin in
pharmaceutical texts because it was never ment to be used as a drug.  you
can probably  find some info by looking up chemical name (see above) in a
Merck Index which list all chemical compounds.  Also you may look in
medical text under cholinesterace inhibitors.  You may want to contact the
CDC in Atlanta, NIH, or Dept. of Defense they would have the most data on
nerve agents and their side effects. Good Luck.  If I can be of any



Sun, 07 Sep 1997 04:42:03 GMT
 sarin - tokyo incident
: My wife has been exposed to sarin, in the incident in Tokyo this monday.
: Does anyone know anything about this drug? Or where I might find information?
: How it might affect a fetus? Information is a little hard to come by in Japan.
: She seems to be recovering well, but I am worried about long-term consequences.

well, i know that the chemical name for sarin is
methylisopropylfluorophosphate (MIFP) if that's any help for looking
information up.



Sun, 07 Sep 1997 07:09:18 GMT
 sarin - tokyo incident
   >My wife has been exposed to sarin, in the incident in Tokyo this monday.
   >Does anyone know anything about this drug? Or where I might find information?
   >How it might affect a fetus? Information is a little hard to come by in Japan.
   >She seems to be recovering well, but I am worried about long-term consequences.

Wow.  I can appreciate your anxiety.  I'm glad to hear your wife is
doing well.

Sarin is a so-called "nerve gas", an organophosphate compound which
is in the same family as the organophosphate insecticides (parathion,
diazinon, malathion, just to name a few.)  The only difference is
that sarin is far, far more toxic than even the terribly toxic
insecticide parathion, and its vapor pressure is such that it can be
used as a gas in warfare, so it is more lethal than the pesticides, which
ordinarily must come in contact with the skin to cause toxicity.
It is still amazing that more people didn't die in Tokyo, because
as little as 1mg of the agent can kill a person.

All of these agents produce their immediate toxic effects by
permanently disabling the enzyme cholinesterase, which splits
the neurotransmitter acetylcholine into choline and acetate,
thereby terminating its effects.  Acetylcholine is the neuro-
transmitter at the motor endplate (where voluntary muscles
are innervated), at parasympathetic neurons and at sympathetic
ganglia.  It is also a neurotransmitter in certain areas within
the brain.

When cholinesterase is destroyed by an organophosphate agent, the
neurotransmitter builds up at those synapses which use acetylcholine
for communication.  The net result is a "cholinergic crisis" from
excessive stimulation.  At motor end plates, you first get a burst of
activity, and then paralysis, as the muscles become permanently
depolarized.  Since this can include the diaphragm, this paralysis
can lead to death from anoxia.  Additionally, the parasympathetic nervous
system is overstimulated, leading to sweating, salivation and pinpoint
pupils with difficulty accomodating between near and far.  There can
also be central nervous system effects from the accumulation of
acetylcholine, such as convulsions and coma.

The key is that these organophosphates have a similar affinity
for the active site on the cholinesterase enzyme as acetylcholine
does.  However, once in the site, the phosphorus covalently
bonds to a serine residue, wrecking the enzyme and knocking it
permanently out of commission (until new enzyme is synthesized.)
(But see below...)

Now, most of the research on this stuff and their toxicity focuses
on the acute effects of these agents in poisoning.  Basically, if
you have received appropriate supportive care as needed and haven't
died, depending on the severity of the exposure, most of the signs
and symptoms should be over with within a week or so, though there
have been some case reports of sequelae lasting for as long as a
couple of months.  (It can sometimes take that long for cholinesterase
levels to get back to normal in severe exposures.  New enzyme has
to be synthesized to replace that which was knocked out by the
cholinesterase inhibitor.)

The treatment of such an exposure involves giving atropine, an
anticholinergic agent which blocks one type of receptor for
acetylcholine -- the eponymous _muscarinic_ receptor, found in
the parasympathetic nervous system and centrally in the brain,
after muscarine, a cholinergic agent found in some mushrooms
which stimulates only those receptors.  The other class of
acetylcholine receptor is known as the _nicotinic_ receptor,
after the drug nicotine; nicotinic receptors are found in the
brain, at the motor endplate and at sympathetic ganglia.
Additionally, a drug called 2-PAM or pralidoxime is given
quickly after exposure to "reactivate" the phophorylated enzyme.
Pralidoxime is a bit like a chemical crowbar which manages to
pry the phosphate out of the active site and regenerate a
working enzyme again.

In wartime, soldiers are given a kit containing both of these {*filter*};
most recently in the Gulf War, the Army also attempted to pretreat
soldiers with atropine and with anticholinergic carbamate {*filter*} such as
pyridostigmine.  Carbamates like this are also cholinesterase
inhibitors (pretty non-intuitive, eh?), but they're _competitive_
inhibitors--they don't bind covalently to the enzyme in any permanent
fashion, they just make the enzyme unavailable while the drug
resides in the active site.  The idea, I guess, is that it's better
to occupy some active sites on your cholinesterase enzymes temporarily
than to keep them open for an unwanted visit from a gas like sarin
and guarantee they'll be knocked out for good.  This last decision
to pretreat as a prophylactic against poison gas was fairly controversial,
since the regimen is a bit toxic and makes the soldier feel lousy.

Side digression: one of the side effects of organophosphate poisoning
is salivation, due to excessive stimulation of the salivary gland by
its parasympathetic innervation.  When you take most antihistamines
or tricyclic antidepressants, you often get a dry mouth.  That's
because these {*filter*} have an atropine-like action and block the
muscarinic receptors which are ordinarily stimulated to cause the
salivary gland to produce saliva.

What isn't addressed all that well are longer-term effects from
such an acute exposure.  There are some organophosphate pesticides
which can have long term neurological effects which proably aren't
due to their ability to inhibit cholinesterase.  There are also
isolated case reports of people experiencing longer term effects
after such an acute exposure.  I don't know anything about fetal
exposure to such an agent, though there are probably reports on
this (through accidental pesticide poisoning) in the literature.
I can appreciate your concern here, and I fear that this is an
area where there hasn't been a whole lot of research except in
cases of accident.

If I were you, I'd try to reach a clinical toxicologist in
a local medical school or medical center in your area and
relate your concerns.  You'd probably also want to talk to
your wife's ob/gyn about this unfortunate event as well.
Good luck.

--
Steve Dyer



Sun, 07 Sep 1997 13:47:40 GMT
 sarin - tokyo incident
According to the 11th edition of the Merck Index,  Sarin can have toxic
effects similar to, but more severe than, parathion.  You might try
locating a copy of the article:  "Some Aspects of the Chemistry and Toxic
Action of Organic Compounds Containing Phosphorus and Fluorine (Cambride,
1957) p 92 sqq:  Bryant et al., J. Chem. Soc. 1960, 1553.

According to "The Pharmacological Basis of Therapeutics." by Alfred
Goodman Gilman et al. copyright 1985. p 119.

"After local exposure to vapors or aerosols or after their inhalation,
ocular and respiratory effects generally appear firs.  Ocular effects
include marked miosis, ocular pain, conjunctival congestion, diminished
vision, ciliary spasm, and brow ache.  With acute systemic absorption,
miosis may not be evident due to sypathetic discharge in response to the
hypotension.  In addition to rhinorrhea and hyperemia of the upper
respiratory tract, respiratory effects consist in "tightness" in the chest
and wheezing respiration, due to the combination of bronchoconstriction
and increased bronchial secretion.  Gastrointestinal symptoms occur
earliest after ingestion, and include anorexia, nausea and vomiting,
abdominal cramps, and diarrhea.  With percutaneous absorption of liquid,
localized sweating and muscular fasciculation in the immediate vicinity
and are generally the earliest manifestations."  

As for the effects on an unborn fetus, I don't know for sure what or if
there are/would be any untoward effects...it will greatly depend on the
trimester of the pregnancy.  My suggestion would be that any pregnant
women exposed to this compound should be followed very closely by their
O.B.Gyn. (their obstetrician).

You might consider contacting a hospital librarian to have an on-line
search done on this topic.  Any teaching hospital should be able to assist
you with such a search although there may be a small fee.  

I wish you the best.



Tue, 09 Sep 1997 14:33:20 GMT
 sarin - tokyo incident
Thank you for your detailed reply.  Medical information has been hard to get
here in Tokyo, compounded by the unwillingness of Japanese doctors to discuss a
patient's condition with the patient or family. We have been in touch with Army
doctors, and my wife's ob/gyn doctor, and all seems to be getting better, apart
from lingering miosis. Again, thanks.


Wed, 10 Sep 1997 17:02:40 GMT
 sarin - tokyo incident

Quote:

>after such an acute exposure.  I don't know anything about fetal
>exposure to such an agent, though there are probably reports on
>this (through accidental pesticide poisoning) in the literature.
>I can appreciate your concern here, and I fear that this is an
>area where there hasn't been a whole lot of research except in
>cases of accident.
>If I were you, I'd try to reach a clinical toxicologist in
>a local medical school or medical center in your area and
>relate your concerns.  You'd probably also want to talk to
>your wife's ob/gyn about this unfortunate event as well.
>Good luck.
>--
>Steve Dyer


        When my mom (dear mommy :) was about three months or earlier
pregnant with me,
        a crop duster flew low over the road she was driving on and
she had to turn on the windshield wipers as a result.

        I now am missing the bulk of my pectoralis major muscle on
the right hand side, plus some other teratologies.

I do not know what the relationship is, if there is any, but it makes
me wonder.

        Also though, my dad tells me that when he was a kid they
used to play in the DDT sprayers since it was the "wonder"
chemical that was going to save the world.

So.............................

I just live with it.  Hardly ever notice it except in my ego anyway.

Peter Jordan



Wed, 10 Sep 1997 15:27:11 GMT
 sarin - tokyo incident


Quote:

>: My wife has been exposed to sarin, in the incident in Tokyo this monday.
>: Does anyone know anything about this drug? Or where I might find information?
>: How it might affect a fetus? Information is a little hard to come by in Japan.
>: She seems to be recovering well, but I am worried about long-term consequences.

>well, i know that the chemical name for sarin is
>methylisopropylfluorophosphate (MIFP) if that's any help for looking
>information up.

From the Merck Index Eleventh Edition 1989

Quote:
>my editorial comments in <

Entry  8332 page 1328
Sarin- Methylphosphonoflouridic Acid 1-methyl-ethyl ester (IUPAC name)

C4H10FO2P
mol wt. 140.09 c 34.29% H7.20% F13.56% O22.84% P22.11%

Nerve Gas:

Documentation: Holmstedt, Acta physiol. Scand. 25, suppl. 90,
p 106 (1951). Protar 14, 113 (1948); 16, 131 (1950).
See also references and prepartions given under Tabun.
Additional References on synthesis: Schrader, B.I.O. S.
714, 41(1947).

Quote:
>Looks like a major book reference<

B.C. Saunders, Some Aspects of Chemistry and Toxic Action of
Organic Compounds Containing Phosphorous and Flourine (Cambridge
1957) p 92 sqq.

Quote:
>Also look at:<

Bryant et al. J Amer Chem Soc. 1960, 1553
Brief Review: Schrader, Die Entwicklung neuer insektizder
Phosophosaure-Ester (Verlage Chemie, Weinheim 1963) p. 4
Abs config: Benschop et al., Rec. Trav Chim. 87, 387 (1968)

Quote:
>Other Info:<

Liquid densit 1.10 mp -57C bp(1 atm) 147C bp(16mm Hg) 56C
Misible>mixable< and and hydrolyzed by water. Rapidly
hydrolyzed by dil. aq. sodium hydroxide or sodium carbonate
forming relatevilely non-toxic products. Water Alone removes
the flourine atom atom producing the non toxic acid
CH3PO[OCH(CH3)2]OH. LD50 >(Lethal Dose 50% of test population
of mentioned animal)< i.p. in mice .42mg/kg B. Holmstedt,
Pharmacol. Rev. 11,567(1957). Lethal dose for humans maybe
as low as 0.01 mg/kg Chem & Eng. News, 31, 4676(1953)

Human Toxicity: Extremely active cholinesterase inhibitor.
Toxic Effects similair to, but more sever than parathion
(which one should check the references on)

USE: Chemical Warfare Agent

------

Hope this helps,
Have Fun,
Sends Steve



Sun, 14 Sep 1997 12:51:02 GMT
 
 [ 8 post ] 

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