<unk>  (red), acetylcholinesterase (yellow), acetylcholine (blue) Like some other nerve agents that affect the neurotransmitter acetylcholine,<unk>  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<unk>  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<unk> , 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.<unk>  has a high volatility (ease with which a liquid can turn into vapour) relative to similar nerve agents, making inhalation very easy, and may even absorb through the skin. A person's clothing can release<unk>  for about 30 minutes after it has come in contact with<unk>  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<unk>  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.<unk>  acts on acetylcholinesterase by forming a covalent bond with the particular<unk> e residue at the active site. Fluoride is the leaving group, and the resulting organo-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. Diagnostic tests Controlled studies in healthy men have shown that a nontoxic 0.43 mg oral dose administered in several portions over a 3-day interval caused average maximum depressions of 22 and 30%, respectively, in plasma and erythrocyte acetylcholinesterase levels. A single acute 0.5 mg dose caused mild symptoms of intoxication and an average reduction of 38% in both measures of acetylcholinesterase activity.<unk>  in blood is rapidly degraded either in vivo or in vitro. Its primary inactive metabolites have in vivo serum half-lives of approximately 24 hours. The serum level of unbound isopropyl methylphosphonic acid (IMPA), a<unk>  hydrolysis product, ranged from 2–135 μg/L in survivors of a terrorist attack during the first four hours post-exposure.<unk>  or its metabolites may be determined in blood or urine by gas or liquid chromatography, while acetylcholinesterase activity is usually measured by enzymatic methods. A newer method called "fluoride regeneration" or "fluoride reactivation" detects the presence of nerve agents for a longer period after exposure than the methods described above. Fluoride reactivation is a technique that has been explored since at least the early 2000s. This technique obviates some of the deficiencies of older procedures.<unk>  not only reacts with the water in the blood plasma through hydrolysis (forming so-called 'free metabolites'), but also reacts with various proteins to form 'protein adducts'. These protein adducts are not so easily removed from the body, and remain for a longer period of time than the free metabolites. One clear advantage of this process is that the period, post-exposure, for determination of<unk>  exposure is much longer, possibly five to eight weeks according to at least one study. Toxicity As a nerve gas,<unk>  in its purest form is estimated to be 26 times more deadly than cyanide. The LD50 of subcutaneously injected<unk>  in mice is 172 μg/kg.<unk>  is highly toxic, whether by contact with the skin or breathed in. The toxicity of<unk>  in humans is largely based on calculations from studies with animals. The lethal concentration of<unk>  in air is approximately 28 – 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, lower 28 mg/m3 value is for general population). This number represents the estimated lethal concentration for 50% of exposed victims, the LCt50 value. The LCt95 or LCt100 value is estimated to be 40 – 83 mg per cubic meter for exposure time of two minutes. Calculating effects for different exposure times and concentrations requires following specific toxic load models. In general, brief exposures to higher concentrations are more lethal than comparable long time exposures to low concentrations. There are many ways to make relative comparisons between toxic substances. The list below compares<unk>  to some current and historic chemical warfare agents, with a direct comparison to the respiratory LCt50: * Hydrogen cyanide, 2,860 mg·min/m2 –<unk>  is 81 times more lethal * Phosgene, 1,500 mg·min/m2 –<unk>  is 43 times more lethal * Sulfur mustard, 1,000 mg·min/m2 –<unk>  is 28 times more lethal * Chlorine, 19,000 mg·min/m2 –<unk>  is 543 times more lethal
Sarin
Nocebo
Heparin
Prokarin
Hirudin
Imiprothrin
Cephem
Palladin