Organophosphate poisoning from insecticides

Organophosphates. The acute toxicity of organophosphate pesticides is basically derived from the anticholinesterase property of these chemicals. This property, which results in accumulation of acetylcholine at synapses and myoneural junctions, is responsible for both the insecticidal activity and mammalian toxicity. Early symptoms of organophosphate poisoning in humans include, among others, miosis (pinpoint pupils) and blurred vision, and a response known as the SLUD (salivation, lacrimation, urination, and diarrhea) syndrome all of these are the result of muscarinic effects (12-15). Clinical manifestations of more severe poisoning involve predominantly nicotinic and central effects which include convulsions, paralysis, depressed respiration and cardiovascular functions, and coma (12-15). Death is usually due to respiratory failure, accompanied by cardio-vascular failure (13). 

In a 1991 study, every surveyed pesticide spray applicator working regularly with dimethoate reported suffering often from nausea, sore eyes and headaches, the symptoms of organophosphate poisoning. Other studies have indicated that this insecticide can cause anxiety and depression in people who have been regularly exposed. 

PAM CL Pralidoxime, chloride, Protopam , is an antidote to organophosphate poisoning such as might result from exposure to nerve agents or some insecticides. The drug, which helps restore an enzyme called acetylcholinesterase, must be used in conjunction with atropine to be effective. Restores normal control of skeletal muscle contraction (relieves twitching and paralysis). 

Milk from poisoned animals should not be used until analysis indicates no evidence of residue. Residues in foods of animal origin are usually not a problem because organophosphate and carbamate insecticides are rapidly metabolized and excreted. 

Clinical signs are indistinguishable from organophosphate poisoning. Muscarinic signs include salivation, lacrimation, urinary incontinence, and defecation. Nicotinic signs include muscle tremors and fascicula-tions, convulsions, and respiratory failure (Mahmood and Carmichael, 1986). The muscarinic effects of ana-toxin-a(s) can be suppressed by atropine (Cook et al., 1990), but it is relatively resistant to oxime reactivation, compared with typical organophosphate insecticides, because of the formation of an enzyme-adduct (Hyde and Carmichael, 1991). 

Irreversible anticholinesterases include the organophosphorus inhibitors and ambenonium, which irreversibly phosphorylate the esteratic site. Such drugs have few clinical uses but have been developed as insecticides and nerve gases. Besides blocking the muscarinic receptors with atropine sulphate in an attempt to reduce the toxic effects that result from an accumulation of acetylcholine, the only specific treatment for organopho-sphate poisoning would appear to be the administration of 2-pyridine aldoxime methiodide, which increases the rate of dissociation of the organophosphate from the esteratic site on the enzyme surface. 

C. Bronchoconstriction and secretion and muscular weaknesses occur from acetylcholine accumulation after inhibition of acetylcholinesterase. Parathion is an organophosphate insecticide that inhibits acetylcholinesterase, and it is readily available. Poisoning with compound 1080 (fluorocitrate) inhibits mitochondrial respiration and causes seizures and car-... 

Esterase activity is important in both the detoxication of organophosphates and the toxicity caused by them. Thus brain acetylcholinesterase is inhibited by organophosphates such as paraoxon and malaoxon, their oxidized metabolites (see above). This leads to toxic effects. Malathion, a widely used insecticide, is metabolized mostly by carboxylesterase in mammals, and this is a route of detoxication. However, an isomer, isomalathion, formed from malathion when solutions are inappropriately stored, is a potent inhibitor of the carboxylesterase. The consequence is that such contaminated malathion becomes highly toxic to humans because detoxication is inhibited and oxidation becomes important. This led to the poisoning of 2800 workers in Pakistan and the death of 5 (see chap. 5 for metabolism and chap. 7 for more details). 

It is difficult to obtain figures that accurately reflect the incidence of pesticide poisoning, and the number of documented cases of direct human poisoning in the USA varies from source to source. It was estimated that there are 100,000 nonfatal cases of human poisoning each year from pesticide exposure (7). In 1973 there were 1,A7A cases of occupational illness associated with pesticide exposure in California (8). Organophosphate insecticides are a major cause of occupational poisoning. 

A crop duster pilot has been accidentally exposed to a high concentration of an agricultural organophosphate insecticide. If untreated, the cause of death from such a poisoning would probably be... 

In summary, studies intended to examine the neuropsychiatric effects of organophosphate compounds vary in their adequacy, and in some instances the results are contradictory. Most studies agree, however, that acute neuropsychiatric effects result from exposure to both insecticides and nerve agents. These effects include inability to concentrate, memory problems, sleep disturbances, anxiety, irritability, depression, and problems with information processing and psychomotor tasks. With pesticides, these effects do not occur in the absence of the conventional signs of poisoning. 

The organophosphate insecticides, when introduced, about 1945, made a large and welcome addition to what was available. Because a fuller account is given in Section 13.3, it need be said here only that they are nerve poisons which initially act in a quite different way from the pyrethroids and chlorinated hydrocarbons, for they are inhibitors of acetylcholinesterase. The earliest examples, discovered in Germany by Schrader, were as toxic to the spraymen as to the insects. Little by little, adequate selectivity was built into the molecules, and control over their half-life in the field became part of the molecular design also. 

Unlike the chlorinated hydrocarbons and pyrethroids, the organophosphate insecticides tend towards hydrophilicity, and the more hydrophilic types are taken up by plants from the soil. These systemic insecticides have made a great contribution to selectivity because they poison only those insects that bite the plant. The organophosphates were later joined by the similarly acting carbamate insecticides, less hydrophilic but also less persistent. They are described in Section 13.3. 

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