Cholinesterase reactivation in organophosphorus poisoned patients depends on the plasma concentrations of the oxime pralidoxime methylsulphate and of the organophosphate

Willems, Jean; Bisschop, Herbert C. De; Verstraete, Alain G.; Declerck, C.; Christiaens, Yannick; Vanscheeuwyck, P.; Buylaert, Walter; Vogelaers, Dirk; Colardyn, Francis

doi:10.1007/bf01973675

Cited by 88 publications

(48 citation statements)

References 22 publications

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“…It is reasonable to expect that the concentration of methyl parathion, methyl paraoxon or both must fall below a certain level to allow spontaneous reactivation of cholinesterase to outpace inhibition. Such seems to be the case in humans in whom reactivation of cholinesterase with pralidoxime methylsulfate was dependent upon plasma organophosphate concentration [42]. Dealkylation of the phosphoryl-cholinesterase complex may also occur, resulting in an 'aged' enzyme that does not readily reactivate [3].…”

Section: Discussionmentioning

confidence: 96%

A Comparison of Cholinesterase Activity after Intravenous, Oral or Dermal Administration of Methyl Parathion

Krämer¹,

Wellman²,

Zhu³

et al. 2002

J Biomed Sci

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Time-dependent changes in blood cholinesterase activity caused by single intravenous, oral or dermal administration of methyl parathion to adult female rats were defined. Intravenous and oral administration of 2.5 mg/kg methyl parathion resulted in rapid (<60 min) decreases in cholinesterase activity which recovered fully in vivo within 30–48 h. In contrast, spontaneous reactivation of cholinesterase in vitro was complete within 6 h at 37°C. Dermal administration of methyl parathion caused dose-dependent inhibition of cholinesterase activity which developed slowly (≧6 h) and was prolonged (≧48 h). Time- and route-dependent effects of methyl parathion on cholinesterase activity in brain and other tissues generally paralleled its effects on activity in blood. In conclusion, pharmacodynamics of methyl parathion differ substantially with route of exposure. Recovery of cholinesterase in vivo after intravenous or oral exposure may partially reflect spontaneous reactivation and suggests a rapid clearance of methyl parathion or its active metabolite methyl paraoxon. The more gradual and prolonged inhibition of cholinesterase caused by dermal administration is consistent with disposition of methyl parathion at a site from which it or methyl paraoxon is only slowly distributed. Thus, dermal exposure to methyl parathion may pose the greatest risk for long-term adverse effects.

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Section: Discussionmentioning

confidence: 96%

A Comparison of Cholinesterase Activity after Intravenous, Oral or Dermal Administration of Methyl Parathion

Krämer¹,

Wellman²,

Zhu³

et al. 2002

J Biomed Sci

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“…82 Nine patients intoxicated with organophosphorus insecticides were treated with PAM-2 methylsulphate (Contrathion) using a dose of 4.42 mg/kg as a bolus injection followed by continuous infusion 2.14 mg/kg/h. 106 In patients with ethylparathion and methylparathion poisonings, enzyme reactivation could be obtained in some at oxime concentrations as low as 2.88 mg/L. In others, however, oxime concentration as high as 14.6 mg/L were ineffective.…”

Section: Mechanism Of Action Of Pyridinium Oximesmentioning

confidence: 99%

Unequal Efficacy of Pyridinium Oximes in Acute Organophosphate Poisoning

Antonijević¹,

Stojiljković²

2007

Clinical Medicine & Research

214

159

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“…Bowever, the fact that no metabolites were detected is not a sure indication that they are not produced. In mammals, it has been shown that in plasma, aetive oxygen analogues are present at levels 30-100 times below parent compound concentrations (Willems et al 1993). Because of the detection limit in this study of 0.5 ng, potentially existing metabolites would have been detected only if they were present at levels 25 times below parent compound concentrations.…”

Section: Discussionmentioning

confidence: 99%

Toxicity of Organophosphorus Insecticides in the Zebra Mussel, Dreissena polymorpha P.

Dauberschmidt¹,

Dietrich²,

Schlatter³

1996

Archives of Environmental Contamination and Toxicology

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Abstract. The 96-h toxieity of four organophosphates (thiometon, disulfoton, malathion, and demeton-S-methyl, the oxygen analogue of thiometon) in the freshwater bivalve molluse Dreissena polymorpha was tested using different nominal concentrations ranging between 6 and 50 mglL. No mortalities were observed in musseis exposed to malathion and demeton-S-methyl (26 mglL and 6 mglL, respectively), and at the lowest eoncentrations of thiometon and disulfoton (6 and 10 mglL, respectively). At higher thiometon and disulfoton concentrations, mortalities occurred. At the highest concentrations of 50 mg thiometonIL and 30 mg disulfotonIL, mussei mortalities of 88 and 93%, respectively, were determined. Organophosphate concentrations of up to a factor 10 times higher than in the ambient water were found in exposed musseis, irrespective of whether they were alive or dead. The search for organophosphate metabolites via GCIMS analysis of mussei tissue extraets was negative, suggesting lacking or low oxidative activation of the insecticides used. The mollusc is highly resistant to toxie effects of organophosphate insectieides and their biologieal aetive oxygen analogues.On November 1, 1986, a pestieide storing facility at Sandoz in Basel (Switzerland) caught fire. In order to extinguish the fire, water was pumped at high volurnes from the nearby river Rhine. This water found its way back into the river Rhine due to overflowing sewage canals (Capel et al. 1988; Güttinger and Stumm 1992). Along with the fire-extinguishing water, pesticides stored in the affeeted facility were swept into the river. Among these pesticides were organophosphate insectieides, mainly thiometon and disulfoton, mereurial-based fungieides, and herbicides. Consequently, the river Rhine ecosystem *Present address: Department of Environmental and OccupationalHealth, University of Pittsburgh, Pittsburgh, PA 15238, USACorrespondence to: C. Dauberschmidt faced high water eoncentrations of these pesticides. Measured peak eoncentrations elose to the source of contamination were 500 J.1glL and 600 IJ.-glL for thiometon and disulfoton, respectively. These pestieide coneentrations severely affected insect, erustaeean, and fish populations of the Rhine ecosystem. In particular, eels (Anguilla anguilla L.) appeared to be highly susceptible to organophosphate intoxication, as fish of this speeies were found dead up to 400 km downstream of the souree of contamination (Güuinger and Stumm 1992).Based on the ehemieal eharaeteristies of these compounds, it was assumed they would undergo quick hydrolysis and biodegradation, and would not remain in the Rhine sediments (EAWAG 1987). However, up to 3 1/2 months following the incident, eopious concentrations of unhydrolyzed parent compound of the major contarninants, thiometon and disulfoton, were found in the Rhine river sediment near the site of original eontamination (430 ppm and 3,000 ppm, respectively, Institute of Toxicology, unpublished data).In addition to the initial fish deaths, unusually high numbers of dead diving...

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Cholinesterase reactivation in organophosphorus poisoned patients depends on the plasma concentrations of the oxime pralidoxime methylsulphate and of the organophosphate

Cited by 88 publications

References 22 publications

A Comparison of Cholinesterase Activity after Intravenous, Oral or Dermal Administration of Methyl Parathion

A Comparison of Cholinesterase Activity after Intravenous, Oral or Dermal Administration of Methyl Parathion

Unequal Efficacy of Pyridinium Oximes in Acute Organophosphate Poisoning

Toxicity of Organophosphorus Insecticides in the Zebra Mussel, Dreissena polymorpha P.

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