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View Full Version : [Clinical Toxicology] Anticholinesterase Insecticides Poisoning



TomHsiung
Mon 14th October '13, 12:17am
Mechanism of Toxicity

Anticholinesterase insecticides phosphorylate the active site of cholinesterase in all parts of the body. Inhibition of this enzyme leads to accumulation of acetylcholine at affected receptors and results in widespread toxicity.

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Pathogenesis of life-threatening effects of organophosphate poisoning.

http://accesspharmacy.com/loadBinary.aspx?name=dipi8&filename=dipi8_c014f003.gifRisk Assessment

Measurement of acetylcholinesterase activity at the neuronal synapse is not feasible clinically. Cholinesterase activity can be measured in the blood as the pseudocholinesterase activity of the plasma and acetylcholinesterase activity in the erythrocyte.

Severity of poisoning can be estimated roughly by the extent of depressed activity in relation to the low normal range. The intrinsic activity of acetylcholinesterase may be depressed in some individuals, but the absence of any manifestations in most people dose not permit recognition of the deficiency in the general population.

Therapy should not be delayed pending laboratory confirmation when insecticide poisoning is clinically suspected.
Management of Toxicity

People handling the patient should wear gloves and aprons to protect themselves against contaminated clothing, skin, or gastric fluid of the patient. Because many insecticides are dissolved in a hydroacrbon vehicle, there is an additional risk of pulmonary aspiration of the hydrocarbon leading to pneumonitis.

The risks and benefits of gastric decontamination (e.g., gastric lavage, activated charcoal) should be considered carefully and should involve consultation with a poison control center or clinical toxicologist.

If the poison has been ingested within the hour, gastric lavage should be considered and followed by the administration of activated charcoal. For the patient with skin contamination, contaminated clothing should be removed and the patient washed with copious amounts of soap and water before he or she is admitted to the emergency department or other patient care area. An alcohol wash may be useful for removing residual insecticide because of its lipophilic nature.

Supportive therapy should include maintenance of airway, provision of adequate ventilation, and establishment of an intravenous line.

Pharmacologic management of organophosphate intoxication relies on administration of atropine and pralidoxime. Atropine has no effect on inhibited cholinesterase, but it competitively blcoks the actions of acetylcholine on cholinergic and some central nervous system receptors. It thereby alleviates bronchospasm and reduces bronchial secretions. Although atropine has little efffect on the flaccid muscle paralysis or the central respiratory failure of severe poisoning, it is indicated in all symptomatic patients and can be used as a diagnostic aid. It should be given intravenously and in larger than conventional doses of 0.05 to 0.1 mg/kg in children younger than 12 years and 2 to 5 mg in adolescents and young adults. It should be repeated at 5- to 10-minute intervals until brochial secretions and pulmonary rales resolve. Therapy may require large doses over a period of several days until all absorbed organophosphate is metabolized, and acetylcholinesterase activity is restored.

Restoration of enzyme activity is necessary for severe poisoning, characterized by reduction of cholinesterase activity to <20% of normal, profound weakness, and respiratory distress. Pralidoxime breaks the covalent bond between the cholinesterase and organohosphate and regenerates enzyme activity. Organophosphate-cholinesterase binding is reversible initially, but it gradually becomes irreversible. Therefore, therapy with pralidoxime should be initiated as soon as possible, preferably within 36 to 72 hours of exposure. The drug should be given at a dose of 25 to 50 mg/kg up to 1 g intravenously over 5 to 20 minutes. If muscle weakness persists or recurs, the dose can be repeated after 1 hour and again if needed. A continuous infusion of pralidoxime has been shown to be effective in adults when administered at 2 to 4 mg/kg/h preceded by a loading dose of 4 to 5 mg/kg and in children at 10 to 20 mg/kg/h with a loading dose of 15 to 50 mg/kg.

Both atropine and pralidoxime should be given together because they have complementary actions. One of the pitfalls of therapy is the delay in administering sufficient doses of atropine or pralidoxime. The adverse effects of atropine and pralidoxime, predictable extensions of their anticholinergic actions, are minimally important compared with the life-threatening effects of severe anticholinesterase poisoning and can be minimized easily by decreasing the dose.