pralidoxime and Drug-Related-Side-Effects-and-Adverse-Reactions

The use of organophosphorus pesticides results in toxicity risk to non-target organisms. Organophosphorus compounds share a common mode of action, exerting their toxic effects primarily via acetylcholinesterase (AChE) inhibition. Consequently, acetylcholine accumulates in the synaptic clefts of muscles and nerves, leading to overstimulation of cholinergic receptors. Acute cholinergic crisis immediately follows exposure to organophosphate and includes signs and symptoms resulting from hyperstimulation of central and peripheral muscarinic and nicotinic receptors. The current view of the treatment of organophosphate poisoning includes three strategies, i.e. the use of an anticholinergic drug (e.g., atropine), cholinesterase-reactivating agents (e.g., oximes) and anticonvulsant drugs (e.g., benzodiazepines). Oximes, as a part of antidotal therapy, ensure the recovery of phosphylated enzymes via a process denoted as reactivation of inhibited AChE. However, both experimental results and clinical findings have demonstrated that different oximes are not equally effective against poisonings caused by structurally different organophosphorus compounds. Therefore, antidotal characteristics of conventionally used oximes can be evaluated regarding how close the certain substance is to the theoretical concept of the universal oxime. Pralidoxime (PAM-2), trimedoxime (TMB-4), obidoxime (LüH-6), HI-6 and HLö-7 have all been demonstrated to be very effective in experimental poisonings with sarin and VX. TMB-4 and LüH-6 may reactivate tabun-inhibited AChE, whereas HI-6 possesses the ability to reactivate the soman-inhibited enzyme. An oxime HLö-7 seems to be an efficient reactivator of AChE inhibited by any of the four organophosphorus warfare agents. According to the available literature, the oximes LüH-6 and TMB-4, although relatively toxic, are the most potent to induce reactivation of AChE inhibited by the majority of organophosphorus pesticides. Since there are no reports of controlled clinical trials on the use of TMB-4 in human organophosphate pesticide poisoning, LüH-6 may be a better option.

Topics: Acetylcholinesterase; Antidotes; Chemical Warfare Agents; Cholinesterase Reactivators; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Insecticides; Obidoxime Chloride; Organophosphate Poisoning; Organothiophosphorus Compounds; Oximes; Pralidoxime Compounds; Sarin; Trimedoxime

Topics: Atropine; Child; Diphosphates; Drug-Related Side Effects and Adverse Reactions; Organophosphate Poisoning; Oximes; Parathion; Phosphorus; Poisons; Pralidoxime Compounds; Pyridines; Toxicology

Topics: Drug-Related Side Effects and Adverse Reactions; Methane; Organophosphate Poisoning; Phosphorus; Poisons; Pralidoxime Compounds

Topics: Atropine; Drug-Related Side Effects and Adverse Reactions; Iodides; Organophosphate Poisoning; Oximes; Phosphorus; Poisons; Pralidoxime Compounds; Pyridines

Topics: Drug-Related Side Effects and Adverse Reactions; Organophosphate Poisoning; Phosphates; Picolines; Pralidoxime Compounds

Topics: Diacetyl; Drug-Related Side Effects and Adverse Reactions; Hydroxylamines; Organophosphate Poisoning; Phosphates; Pralidoxime Compounds; Pyridines

Three oximes, monoisonitrosoacetone (MINA), pyridine-2-aldoxime methiodide (PAM) and diacetylmonoxime (DAM), have been examined in combination with atropine as antidotes in sarin poisoning. When treatment was administered 15 min. before sarin, atropine enhanced the protective effect of MINA and DAM 2 to 3 times and of PAM 9 to 10 times in mice and rats. In mice, rats, and guinea-pigs, atropine increased by no more than 2 times the protective effect of all three oximes when given 30 sec. after sarin. Atropine given to monkeys 1 min. after sarin raised the LD50 approximately 3 times. When given in conjunction with MINA or DAM, the LD50 of sarin was raised 7 to 14 times.

Topics: Animals; Antidotes; Atropine; Cholinesterase Inhibitors; Diacetyl; Drug-Related Side Effects and Adverse Reactions; Guinea Pigs; Hydroxylamines; Mice; Organophosphate Poisoning; Oximes; Phosphates; Pralidoxime Compounds; Rats; Sarin