The Impact of Pesticides - Academy Publish

Asoxime (HI-6)Clinical studies showed that HI-6 dosed at either 250 or 500 mg by intramuscularroute reached plasma concentrations > 4 mg/L in 4-6 minutes. This concentrationwas maintained for 125 minutes following the lower dose (250 mg) and 200 minutesfollowing the higher dose (500 mg) (Kušić et al., 1985; Kušić et al., 1991). Theseauthors have administered HI-6 four times a day as a single intramuscular injectionof 500 mg with atropine and diazepam treatment. Oxime treatment was started onadmission and continued for 2 to 7 days.A clinical study performed on 22 healthy human volunteers did not reveal anyadverse effects when HI-6 was given in doses up to 500 mg by oral route (Jovanovićet al., 1990). HI-6 is considered to be a very promising bispyridinium oxime inmedical treatment following exposure to most nerve agents. A disadvantage of HI-6compared to other available oximes is its lack of stability in aqueous solutions. HI-6was considered to be an effective antidote (in combination with atropine anddiazepam) in treatment of patients poisoned with OP insecticides (Kušić et al.,1991).It is important to note that oximes are not effective for improvement of outcomes ifthe patient develops severe complications such as aspiration pneumonia or hypoxicbrain injury before treatment. Such complications take place with fast-actingpesticides such as parathion and dichlorvos (Eddleston et al., 2008).Clinical experience with pyridinium oximesA particular problem in interpreting the beneficial role and efficacy of oximes inclinical practice is a deficiency of published data, especially those evaluated incontrolled clinical trials. Studies related to the efficacy of oximes in clinical settingshowed the heterogeneity of therapeutic approaches (i.e., dose regimen, oximechoice and final outcome of the treatment). In most reports cited in this sectionchemical structure of OP pesticides was identified in blood/urine and there wereadequate data on therapeutic measures taken.Eddleston et al. (2005b) conducted a prospective study on 802 patients selfpoisonedwith chlorpyrifos, dimethoate, or fenthion. Compared with chlorpyrifos(8.0%), the proportion dying was significantly higher with dimethoate (23.1%) orfenthion (16.2%) as was the proportion requiring endotracheal intubation(chlorpyrifos, 15.0%; dimethoate, 35.2%, fenthion, 31.3%). Patients poisoned bydiethyl OP pesticide (chlorpyrifos) responded well to pralidoxime, whereas thosepoisoned by two dimethyl OP pesticides (dimethoate, fenthion) responded poorly.Poor efficacy of pralidoxime in treatment of human dimethoate and fenthionpoisonings was in agreement with experimental studies conducted by Jokanović andMaksimović (1995) who found that antidotal efficacy of obidoxime, trimedoxime,pralidoxime and HI-6 (given with atropine and diazepam) in rats dosed with 2 LD50of the dimethoate, was low. However, there was a discrepancy between fenthionpoisoned patients and animals in that pralidoxime was ineffective as an antidote inpatients, while the four oximes showed considerable efficacy in rats.Kušić et al. (1991) have tested the oxime HI-6 in OP pesticide poisoning in 60patients. HI-6 was administered four times a day as a single intramuscular injectionof 500 mg with atropine and diazepam treatment. Oxime therapy was started onadmission and continued for 2 to 7 days. Most patients were treated with HI-6 andnine patients severely poisoned with quinalphos were treated with PAM-2 chloride(1000 mg four times per day). HI-6 rapidly reactivated human erythrocyte AChEinhibited by dietoxy OPs (phorate, pyridaphenthion, quinalphos) as well as thatAcademyPublish.org - The Impact of Pesticides51