Pesticide poisoning atropine

Kusic et al. (1991) have tested the oxime HI-6 in OP pesticide poisoning in 60 patients. HI-6 was administered four times a day as a single i.m. injection of 500 mg with atropine and diazepam treatment. Oxime therapy was started on admission and continued for 2 to 7 days. Most patients were treated with HI-6 and nine patients severely poisoned with quinalphos were treated 2-PAM Cl (1,000 mg four times per day). HI-6 rapidly reactivated human red blood cell AChE inhibited by diethoxy OPs (phorate, pyr-idaphenthion, quinalphos) as well as that inhibited by dichlorvos (a dimethoxy OP). AChE inhibited with other dimethoxy OPs (dimethoate and phosphamidon) was reported to be resistant to HI-6 treatment, whereas reactivation with malathion was slow (reactivation half-time 10 h). Both HI-6 and 2-PAM successfully reactivated AChE in quinalphos-poisoned patients, with HI-6 acting as a faster AChE reactivator than 2-PAM. 

Eddlc.ston, M., Buckley, N, A., Checketts, H.. Senarathna, L., Mohained, F., Sheriff, M. H. R., and Dawson, A. (2004). Speed of initial atropinization in significant organophosphorus pesticide poisoning — A Systematic comparison of recommended regimens. Clin. Toxicol. 42, 865-875. 

The phannacokinetics of S- and / -enantiomers of hyoscyamine in humans have been examined by LC-ESI-MS/MS [13]. Plasma supplemented with atropine was incubated with human serum (not containing atropinesterase (AtrE)) and with rabbit serum possessing AtrE (EC 3.1.1.10), which stereospecificaUy hydrolyzes 5-hyoscyamine into tropine and tropic acid while leaving / -hyoscyamine unaffected. The estimation of the differences between the total hyoscyamine content in the aliquots incubated with human and rabbit sera allowed the determination of the remaining / -hyoscyamine and hydrolyzed S-hyoscyamine. Both enantiomers were detected in the MRM mode. The method proved to be reproducible, precise (RSD 2-9 %), accurate (93-101 %), and selective. The enantioselective assay was applied to the analysis of atropine degradation in rabbit semm in vitro as well as to human in vivo plasma samples from a pesticide-poisoned patient treated with atropine. The method was also applied for kinetic studies of atropine administered to swine, where no obvious stereoselective elimination was found [82]. 

Because of its use in OP pesticide poisoning, much has been published about the doses of atropine required, which in some cases can be very high in order to contain a persistent bradycardia. The reader is referred to specialised texts listed at the end of the chapter for more details. 

Oximes Oximes are compounds capable of reactivating, in some cases the complex formed by the OP compounds and acetylcholinesterase. Chemically, oximes are mono or bispyridinium compounds which can bind to the OP-AChE complex and cause the nerve agent molecule to separate from the enzyme. Importantly, oximes can reverse the actions of OP at both muscarinic and nicotinic receptors. Thus, unlike atropine, they act at the neuromuscular junction and can thus reduce the degree of paralysis. They have been shown to be effective in the management of OP pesticide poisoning. However, their effectiveness against nerve... 

Pharmacologically, carbofuran inhibits cholinesterase, resulting in stimulation of the central, parasympathetic, and somatic motor systems. Sensitive biochemical tests have been developed to measure cholinesterase inhibition in avian and mammalian brain and plasma samples and are useful in the forensic assessment of carbamate exposure in human and wildlife pesticide incidents (Bal-lantyne and Marrs Hunt and Hooper 1993). Acute toxic clinical effects resulting from carbofuran exposure in animals and humans appear to be completely reversible and have been successfully treated with atropine sulfate. However, treatment should occur as soon as possible after exposure because acute carbofuran toxicosis can be fatal younger age groups of various species are more susceptible than adults (Finlayson et al. 1979). Carbofuran labels indicate that application is forbidden to streams, lakes, or ponds. In addition, manufacturers have stated that carbofuran is poisonous if swallowed, inhaled, or absorbed through the skin. Users are cautioned not to breathe carbofuran dust, fumes, or spray mist and treated areas should be avoided for at least 2 days (Anonymous 1971). Three points are emphasized at this juncture. First, some carbofuran degradation... 

Symptoms of carbamate intoxication develop earlier than those of OPP poisoning. Hence the exposed worker is more likely to associate his or her symptoms with the pesticide and take earlier evasive action. The antidote of choice for carbamate poisoning is atropine, as with the OPPs. However, the use of PAM is not recommended here, as it may actually prove to be deleterious in some instances (ref. 164,... 

Hydroxybenzoate preservatives inactivate atropine sulfate in physical mixtures. Atropine can be used for treating acetylcholine poisoning. Organophosphorous pesticides are treated by use of diazepam, phenothiazines, and physostigmine.149... 

Willems et al. (1993) reported that ethyl parathion and methyl parathion could be effectively treated with 2-PAM methylsulfate (plasma concentrations 4 mg/1) and atropine when pesticide concentrations in plasma were relatively low. In severe poisoning with pesticide levels in plasma above 30 p.g/1, high 2-PAM concentrations in plasma (14.6 mg/1) did not provide any improvement. In addition, 2-PAM at concentrations of 6.3 mg/1 was not effective in AChE reactivation in dimethoate poisoning where AChE was inhibited with its active metabolite omethoate. 

IPCS (2002). Antidotes for poisoning by organophosphoras pesticides. Monograph on atropine. International Programme on Chemical Safety Evaluation. World Health Organization, Geneva. 

Of direct relevance for pesticide science is the antagonist atropine. This toxicant also binds specifically to the muscarinic receptors where it blocks the effect of ACh. The symptoms are therefore the opposite of those caused by muscarine or acetylcholine (pupil dilation, dry mouth, inhibition of sweating, tachycardia, palpitations, hallucinations, delirium, etc.). Atropine is an important antidote when one is poisoned with a cholinesterase-inhibiting insecticide. 

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