The Impact of Pesticides - Academy Publish

Among the many classes of oximes investigated so far, those with clinicalapplication can be divided in two groups - the monopyridinium and bispyridiniumoximes. Currently, the only used monopyridinium oxime is pralidoxime (PAM-2),while the most significant bispyridinium oximes comprise: trimedoxime (TMB-4),obidoxime (LüH-6, Toxogonin) and HI-6, and their chemical structure is presentedin Figure 3. There is still no international consensus on the choice of most effectiveoxime and on dosing regimen.PralidoximePralidoxime administered to human volunteers at a dose of 10 mg/kg byintramuscular route, produced a plasma concentration of >4mg/L within 5-10minutes and maintained levels above this threshold for an hour (Sidell and Groff,1971). Adverse effects of PAM-2 iodide in volunteers include dizziness, blurredvision, occasional diplopia, impaired accomodation, nausea and headache (Jaggerand Stagg, 1958; Sidell and Groff, 1971).The clinical experience with the use of PAM-2 iodide, given with atropine anddiazepam, in the treatment of the victims of Tokyo sarin attack victims in 1995 wasextremely favourable (Stojiljković and Jokanović, 2005). However, PAM-2 shouldnot be recommended as the drug of choice in poisonong with warfare nerve agentsdue to its lack of efficacy against tabun and soman (Kassa, 2005).In poisoning with OP pesticides pralidoxime chloride should be administered toadults in a dose of 500 mg/h, continuously maintained until clinical improvement isobtained, or 30 mg/kg body weight bolus intravenously over 4 to 6 hours or 8 to 10mg/kg/h intravenously until full recovery occurs. In children, pralidoxime chlorideshould be administered in a dose of 25 mg/kg intravenously for 15 to 30 minutes,followed by a continuous infusion of 10 to 20 mg/kg/h. The therapy can continue for18 hours or longer, depending on the clinical status (IPCS, 1998).It is essential to adjust the appropriate plasma concentration, i.e. for pralidoxime 20to 40 mg/L and for obidoxime about 4 mg/L. This concentration is usually attainedby a daily dose of 10 to 15 g PAM-2 Cl and 0.75 to 1.0 g obidoxime, respectively,either given divided in 4 to 6 single bolus doses or, preferably, by continuousintravenous infusion, following the first loading dose (2 g pralidoxime and 0.25 gobidoxime, respectively) (IPCS, 1998).ObidoximeWhen administered to human volunteers by intramuscular route obidoxime 5 mg/kgproduced a plasma concentration > 4mg/L, from 5 minutes after injection to 3 hours(Sidell and Groff, 1970). Adverse effects of obidoxime in male volunteers weredescribed as pallor, nausea, burning sensation, headache, generalized weakness, sorethroat, and paresthesia of the face (Simon and Pickering, 1976; Eyer, 2003; Marrsand Vale, 2006). Following high doses of obidoxime (several grams per day) inseverely OP-poisoned patients, hepatotoxic effects were occasionally observedincluding increased serum transaminases, jaundice and cholestasis (Eyer, 2003).Obidoxime should be administered in adults at dose of 250 mg given by slowintravenous injection followed by continuous infusion of 750 mg/24h (0.4 mg/kg/h)to reach plasma concentrations of 10-20 μmol/l. Intramuscular dosing is possiblewhen the intravenous route is inaccessible. In children, the dose of obidoxime is 3 to6 mg/kg slowly administered intravenously over at least 5 minutes (IPCS, 1998).AcademyPublish.org - The Impact of Pesticides50