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-Dip

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 ChE action

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- Signs of poisoning-Nicotinic

Organophosphate Insecticides- Signs of poisoning-Depression

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- Lesions

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 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 RBC 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- ChE for Biomonitoring

Organophosphate Insecticides- Treatment Stabilize the animal Atropine sulfate 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

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