Prevenative and Reactionate Medicines

Reactive Antidotes

Antidotes by injection may be used after sarin poisoning has taken place in order to treat a poisoned person. The antidote is a mixture of two components; an oxime and atropine. The oxime is used to reverse the action of the sarin molecule itself, and has the general formula R-CH=NOH. It attacks the phosphorus-oxygen bond which binds the sarin molecule to the acetylcholinesterase enzyme, hydrolysing it to non-toxic products. HI-6 and pralidoxime 2 (P2S) are the main oximes used to combat sarin attack. They have no serious side effects, but they may cause nausea, blackouts, drowsiness, and disturbance of vision. Obidoxime is therefore sometimes used for military personnel, although it can produce hypertension in the patient.

Atropine is used as a simple symptom reliever, to prevent severe muscle contractions which can lead to death. It does nothing to stop the actual attack of acetylcholinesterase, but stops the production of the messenger molecule, acetylcholine, by binding to the receptor. This prevents a dangerous build up of the messenger, giving time for the oxime to work. Atropine can also be used on a long term basis to allow the body to recover a concentration of acetylcholinesterase by itself. This could take many weeks, and the patient may need to be artificially respirated for a short time They may also have severe mental difficulties including amnesia, and suffer from muscle weakness. for up to a year

Ageing

The antidotes must be administered quickly, since a process called "ageing" renders them ineffective within a few minutes. The process involves the phosphorylated enzyme being dealkylated:

Enzyme-O-P(=O)(R₁)(-O R₂)
reacting to give
Enzyme-O-P(=O)(R₁)-OH
The reaction is catalysed by the enzyme itself, and the resultant inhibited enzyme is very resistant to hydrolysis, and reactivation with oxime is no longer possible.

Preventative Antidotes

The major preventative antidote used is a carbamate, pyridostigmine (general formula R₁R₂-N-C(O)-O-R₃). It inhibits acetylcholinesterase, preventing the sarin molecule from attacking it. The pyridostigmine-inhibited enzyme is continuously released to its normal active state and thereby can effectively maintain the transfer of nerve impulses. During treatment, around 75% of enzymes are still uninhibitated, and since only 2-3% are required for full functionality, all normal processes continue. When the sarin attacks, the pyridostigmine prevents inhibitation, but allows a certain amout of activity to continue at the receptor as it releases the enzyme.

Although the Allied governments do not agree, many beleive pyridostigmine to be the cause of Gulf War Syndrome. The British government recently agreed to begin research into the causes of the illness, which are very similar to mild but prolonged sarin exposure.

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