User:Spearlph/sandbox/chem275

Sarin is an extremely toxic synthetic organophosphorus compound. A colourless, odorless liquid, it is used as a chemical weapons due to its extreme potency as a nerve agent. Exposure is lethal even at very low concentrations, where death can occur within one-to-ten minutes after direct inhalation of a lethal dose, due to suffocation from lung muscle paralysis, unless antidotes are quickly administered. People who absorb a non-lethal dose, but do not receive immediate medical treatment, may suffer permanent neurological damage.

Sarin is generally considered a weapon of mass destruction. Production and stockpiling of sarin was outlawed as of April 1997 by the Chemical Weapons Convention of 1993, and it is classified as a Schedule 1 substance.

Health effects
Like some other nerve agents that affect the neurotransmitter acetylcholine, sarin attacks the nervous system by interfering with the degradation of the neurotransmitter acetylcholine at neuromuscular junctions. Death will usually occur as a result of asphyxia due to the inability to control the muscles involved in breathing.

Initial symptoms following exposure to sarin are a runny nose, tightness in the chest, and constriction of the pupils. Soon after, the person will have difficulty breathing and they will experience nausea and drooling. As they continue to lose control of bodily functions, they may vomit, defecate, and urinate. This phase is followed by twitching and jerking. Ultimately, the person becomes comatose and suffocates in a series of convulsive spasms. Moreover, common mnemonics for the symptomatology of organophosphate poisoning, including sarin gas, are the "killer Bs" of bronchorrhea and bronchospasm because they are the leading cause of death, and SLUDGE – salivation, lacrimation, urination, defecation, gastrointestinal distress, and emesis (vomiting). Death may follow in one to ten minutes after direct inhalation.

Sarin has a high volatility (ease with which a liquid can turn into vapour) relative to similar nerve agents, therefore inhalation is very easy and even vapor may immediately penetrate the skin. A person's clothing can release sarin for about 30 minutes after it has come in contact with sarin gas, which can lead to exposure of other people.

Management
Treatment measures have been described. Treatment is typically with the antidotes atropine and pralidoxime. Atropine, an antagonist to muscarinic acetylcholine receptors, is given to treat the physiological symptoms of poisoning. Since muscular response to acetylcholine is mediated through nicotinic acetylcholine receptors, atropine does not counteract the muscular symptoms. Pralidoxime can regenerate cholinesterases if administered within approximately five hours. Biperiden, a synthetic acetylcholine antagonist, has been suggested as an alternative to atropine due to its better blood–brain barrier penetration and higher efficacy.

Mechanism of action
Specifically, sarin is a potent inhibitor of acetylcholinesterase, an enzyme that degrades the neurotransmitter acetylcholine after it is released into the synaptic cleft. In vertebrates, acetylcholine is the neurotransmitter used at the neuromuscular junction, where signals are transmitted between neurons from the central nervous system to muscle fibres. Normally, acetylcholine is released from the neuron to stimulate the muscle, after which it is degraded by acetylcholinesterase, allowing the muscle to relax. A build-up of acetylcholine in the synaptic cleft, due to the inhibition of acetylcholinesterase, means the neurotransmitter continues to act on the muscle fibre, so that any nerve impulses are effectively continually transmitted.

Sarin acts on acetylcholinesterase by forming a covalent bond with the particular serine residue at the active site. Fluoride is the leaving group, and the resulting phosphoester is robust and biologically inactive.

Its mechanism of action resembles that of some commonly used insecticides, such as malathion. In terms of biological activity, it resembles carbamate insecticides, such as Sevin, and the medicines pyridostigmine, neostigmine, and physostigmine.

Toxicity
As a nerve gas, sarin in its purest form is estimated to be 26 times more deadly than cyanide. The LD50 of subcutaneously injected sarin in mice is 172 μg/kg.

Sarin is highly toxic, whether by contact with the skin or breathed in. The toxicity of sarin in humans is largely based on calculations from studies with animals. The lethal concentration of sarin in air is approximately 35 mg per cubic meter per minute for a two-minute exposure time by a healthy adult breathing normally (exchanging 15 liters of air per minute). This number represents the estimated lethal concentration for 50% of exposed victims, the LCt50 value. There are many ways to make relative comparisons between toxic substances. The list below compares sarin to some current and historic chemical warfare agents, with a direct comparison to the respiratory LCt50:


 * Hydrogen cyanide, 2,860 mg·min/m2 – Sarin is 81 times more lethal
 * Phosgene, 1,500 mg·min/m2 – Sarin is 43 times more lethal
 * Sulfur mustard, 1,000 mg·min/m2 – Sarin is 28 times more lethal
 * Chlorine, 19,000 mg·min/m2 – Sarin is 543 times more lethal