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Organophosphate Poisoning in Sheep. Fouad K. Mohammad College of Veterinary Medicine University of Mosul, Iraq 2007. Organophosphate Insecticides- Structure. Derivatives of phosphoric acid:. Organophosphate Insecticides- Examples. Bromophos Coumaphos Crotoxyphos Diazinon
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Organophosphate Poisoning in Sheep Fouad K. Mohammad College of Veterinary Medicine University of Mosul, Iraq 2007
Organophosphate Insecticides- Structure Derivatives of phosphoric acid:
Organophosphate Insecticides-Examples Bromophos Coumaphos Crotoxyphos Diazinon Dichlorvos Malathion
Organophosphate Insecticides-Uses Ectoparasicides: Dips, Sprays, Pour-on, Dusting
Organophosphate Insecticides-Absorption Oral Dermal Inhalational
Organophosphate Insecticides-Toxicity LD50 (lab animals) varies widely 1-3 mg/kg for parathion to 1375 mg/kg for malathion
Organophosphate Insecticides-Mechanism of toxic action OP + ChE IrreversibleInhibition!! Ach accumulation at nerve terminals
Organophosphate Insecticides-Signs of poisoning Muscarinic Nicotinic CNS effects
Organophosphate Insecticides-Signs of poisoning Muscarinic: Salivation, Lacrimation, Bronchoconstriction, Urination, Increase GIT motility
Organophosphate Insecticides-Signs of poisoning Nicotinic: Muscle tremors, Ataxia, Generalized tetany, Weakness and Paresis
Organophosphate Insecticides-Causes of Death Respiratory Depression Bronchconstriction Excessive excretions in the resp. tract Depression of Medulla
Organophosphate Insecticides-Lesions Non-specific: pulmonary edema, blanched mucous membranes, petecheal hemorrhages, increased fluid in the GI tract and increased flaccidity of the intestines.
Organophosphate Insecticides-Diagnosis History ChE Activity in Blood & Tissue Chemical Analysis of tissues Atropine treatment (0.02 mg/kg, iv)
Organophosphate Insecticides-Cholinesterase True Cholinesterase (Brain, RBC) Pseudo Cholinesterase (Plasma, Liver)
Organophosphate Insecticides-Cholinesterase importance 1. Diagnosis of poisoning with ChE inhibitors. 2. Monitoring exposure to ChE inhibitors. 3. Monitoring environmental exposure to ChE inhibitors.
Organophosphate Insecticides-Cholinesterase Methods 1. Spectrophotometric: Ellman Method 2. Electrometric: Michel Method
Organophosphate Insecticides-Principle of the modified electrometric method Cholinesterase + Acetylcholine Choline + Acetic acid Decrease in pH
Organophosphate Insecticides-Cholinesterase Electrometric Method-Mohammad et al., 1997 (J Vet Hum Toxicol) 3 ml distilled water + 0.2 ml aliquot of plasma, erythrocytes or whole blood + 3 ml barbital-phosphate buffer (pH 8.1) Measure pH (pH1) Add 0.1 ml 7.1% acetylcholine iodide Incubate at 37 ºC for 30 min Measure pH (pH2) Cholinesterase activity (∆ pH/30 min) = pH1-pH2- (∆ pH of blank)
Organophosphate Insecticides-Cholinesterase Activity (Delta pH) Sheep Goats Plasma 0.21 0.22 RBC 0.63 0.54 Mohammad et al., 2005 (JAVA) Man: Plasma (0.98), RBC (1.39) Mohammad et al., 2007 (J Med Toxicol)
Organophosphate Insecticides-Cholinesterase Activity Plasma vs. RBC RBC ChE is preferred
Organophosphate Insecticides-Cholinesterase inhibition 25% Exposure 50 – 75 % Poisoning cases > 75% Serious
Organophosphate Insecticides-ChE inhibiton (Mohammad et al., 2007-J Vet Med A)
Organophosphate Insecticides-Biomonitoring Measuring blood ChE activities of ruminants may be used as a biomarker of environmental contamination with pesticides (Munro et al., 1991; Halbrook et al., 1992; Pardio et al., 2001).
Organophosphate Insecticides-Treatment Stabilize the animal Atropine sulfate 0.1-0.2 mg/kg, iv or im Atropinize!! 2-PAM 20 mg/kg, im or iv Diazepam Bath if topical exposure Diphenhydramine HCl??
Organophosphate Insecticides-Drug interactions Drugs to be avoided Morphine Succinylcholine Phenothiazines Barbiturates Carbachol Physostigmine Neostigmine Theophylline