Standard treatment for acute OP intoxication involves pre-treatment with the anticonvulsant pyridostigmine bromide (when possible), and the concomitant administration of atropine and oximes. As a result, acetylcholine accumulates at synapses, inducing convulsions, behavioral impairments, and eventually death, if untreated. OP intoxication is the result of irreversible inhibition of acetylcholinesterase (AChE) via phosphorylation of the active-site serine (Jokanovic and Prostran, 2009). Organophosphates (OP) are commonly used as pesticides and as military nerve agents the latter include sarin, soman, tabun, and VX. The efficacy of oximes depends on (1) the chemical structure of organophosphate, (2) the delay in treatment due to the ageing of the phosphorylated enzyme, (3) the endpoints used to assess their efficacy.ĮMEA/CPMP Guidance Document on the use of Medicinal Products for the Treatment of Patients Exposed to Terrorist Attacks with Chemical Agents (April 2003) (EMA) Summary of clinical and non-clinical studies New York, NY: McGraw-Hill Medical, 2011 p. Goldfranks's Toxicologic Emergencies, 9 th Edition. Nelson LS, Lewin NA, Howland M, Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. However, obidoxime has been detected in cerebrospinal fluid (CSF)and at least one case report describes pralidoxime-induced improvements in mental status and electroencephalograms not attributable to improved ventilation or perfusion. Their quaternary ammonium compound structures are thought to reduce their passage across the blood-brain barrier and prevent CNS effects. Some effects of oximes are not well understood. Oxford, UK: Elsevier, Academic Press, 2009 p. Handbook of Toxicology of Chemical Warfare Agents. In addition to performing /acetylcholinesterase/ reactivation in /organophosphates/ poisoning, oximes might also show some direct pharmacological effects. Phosphorylated oximes are formed during reactivation reaction and some of the appear to be potent inhibitors of /acetylcholinesterase/. The rate of reactivation depends on the structure of the phosphoryl moiety bound to the enzyme, the source of the enzyme, the structure and concentration of oxime which is present at the active site, and the rate of post-inhibitory dealkylation known as aging. Oximes reactivate phosphorylated cholinesterases by displacing the phosphoryl moiety from the enzyme. There is convincing evidence that the antidotal potency of oximes is primarily attributed to their abilities to reactivate the phosphorylated cholinesterases. Product label: PRALIDOXIME CHLORIDE injection Pralidoxime relieves muscarinic signs and symptoms, salivation, bronchospasm, etc., but this action is relatively unimportant since atropine is adequate for this purpose. Because pralidoxime is less effective in relieving depression of the respiratory center, atropine is always required concomitantly to block the effect of accumulated acetylcholine at this site. The drug has its most critical effect in relieving paralysis of the muscles of respiration. Pralidoxime also slows the process of aging of phosphorylated cholinesterase to a non-reactivatable form, and detoxifies certain organophosphates by direct chemical reaction. The destruction of accumulated acetylcholine can then proceed and neuromuscular junctions will again function normally. The principal action of pralidoxime is to reactivate cholinesterase (mainly outside of the central nervous system) which has been inactivated by phosphorylation due to an organophosphate pesticide or related compound. Evidence-based medicine for Chemical Defense - including efficacy and safety A. Chemical Defense therapeutic area(s) - including key possible usesĪntidote for organophosphorous nerve agent poisoning including chlorosarin, cyclosarin (GF), R-33 (VR), R-VX, sarin (GB), tabun (GA), VX, chlorosoman, soman (GD), and organophosphorous pesticides 3. Name of Chemical Defense therapeutic agent/device
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