Worek_1997_Hum.Exp.Toxicol_16_466

Reference

Title : Reappraisal of indications and limitations of oxime therapy in organophosphate poisoning - Worek_1997_Hum.Exp.Toxicol_16_466
Author(s) : Worek F , Backer M , Thiermann H , Szinicz L , Mast U , Klimmek R , Eyer P
Ref : Hum Exp Toxicol , 16 :466 , 1997
Abstract : 1 In vitro studies with human erythrocyte acetylcholinesterase (AChE) and the mouse diaphragm model were performed to unravel the various microscopic reaction parameters that contribute to the dynamic equilibrium of AChE inhibition, ageing and reactivation. These data may help to define more precisely the indications and limitations of oxime therapy in organophosphate (OP) poisoning. 2 Diethylphosphoryl-AChE resulting from intoxications with parathion, chlorpyrifos, chlorfenvinphos, diazinon and other OPs is characterized by slow spontaneous reactivation and low propensity for ageing. This kind of phosphorylated enzyme is particularly susceptible to reactivation by oximes. 3 None of the oximes tested (pralidoxime, obidoxime, HI 6 and HLo 7) can be regarded as a universally suitable reactivator. Obidoxime turned out to be the most potent and most efficacious oxime in reactivating AChE inhibited by various classes of OP insecticides and tabun. Obidoxime, however, was inferior to HI 6 against soman, sarin, cyclosarin and VX. Pralidoxime was generally less potent. 4 The kinetic data of reactivation established for diethylphosphoryl-AChE of human red cells indicate that the usually recommended dosage to attain a plasma concentration of 4 micrograms/ml does not permit exploitation of the full therapeutic potential of the oximes, in particular of pralidoxime. However, in suicidal mega-dose poisoning, oximes, even at optimal plasma concentrations, may be unable to cope with the fast re-inhibition of reactivated AChE in the first days following intoxication. 5 It is suggested that oximes be administered by continuous infusion following an initial bolus dose as long as reactivation can be expected and until permanent clinical improvement is achieved.
ESTHER : Worek_1997_Hum.Exp.Toxicol_16_466
PubMedSearch : Worek_1997_Hum.Exp.Toxicol_16_466
PubMedID: 9292287

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Worek F, Backer M, Thiermann H, Szinicz L, Mast U, Klimmek R, Eyer P (1997)
Reappraisal of indications and limitations of oxime therapy in organophosphate poisoning
Hum Exp Toxicol 16 :466

Worek F, Backer M, Thiermann H, Szinicz L, Mast U, Klimmek R, Eyer P (1997)
Hum Exp Toxicol 16 :466