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Organophosphate Poisoning in Sheep
Fouad K. MohammadCollege of Veterinary Medicine
University of Mosul, Iraq2007
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Organophosphate Insecticides- Structure
Derivatives of phosphoric acid:
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Organophosphate Insecticides-Examples
Bromophos Coumaphos
Crotoxyphos Diazinon
Dichlorvos Malathion
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Organophosphate Insecticides-Uses
Ectoparasicides:
Dips, Sprays,
Pour-on, Dusting
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Organophosphate Insecticides-Dip
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Organophosphate Insecticides-Absorption
Oral
Dermal
Inhalational
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Organophosphate Insecticides-Toxicity
LD50 (lab animals)varies widely 1-3 mg/kg for parathion to 1375 mg/kg for malathion
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Organophosphate Insecticides-Mechanism of ChE action
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Organophosphate Insecticides-Mechanism of toxic action
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Organophosphate Insecticides-Mechanism of toxic action
OP + ChE IrreversibleInhibition!!
Ach accumulation at nerve terminals
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Organophosphate Insecticides-Signs of poisoning
Muscarinic
Nicotinic
CNS effects
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Organophosphate Insecticides-Signs of poisoning
Muscarinic:
Salivation, Lacrimation, Bronchoconstriction, Urination, Increase GIT motility
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Organophosphate Insecticides-Signs of poisoning
Nicotinic:
Muscle tremors, Ataxia, Generalized tetany, Weakness and Paresis
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Organophosphate Insecticides-Signs of poisoning-Nicotinic
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Organophosphate Insecticides-Signs of poisoning-Depression
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Organophosphate Insecticides-Causes of Death
Respiratory DepressionBronchconstriction
Excessive excretions in the resp. tract
Depression of Medulla
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Organophosphate Insecticides-Lesions
Non-specific: pulmonary edema, blanched mucous membranes, petecheal hemorrhages, increased fluid in the GI tract and increased flaccidity of the intestines.
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Organophosphate Insecticides-Lesions
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Organophosphate Insecticides-Lesions
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Organophosphate Insecticides-Diagnosis
History
ChE Activity in Blood & Tissue
Chemical Analysis of tissues
Atropine treatment (0.02 mg/kg, iv)
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Organophosphate Insecticides-Cholinesterase
True Cholinesterase
(Brain, RBC)
Pseudo Cholinesterase (Plasma, Liver)
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Organophosphate Insecticides-Cholinesterase importance
1. Diagnosis of poisoning with ChE
inhibitors.
2. Monitoring exposure to ChE
inhibitors.
3. Monitoring environmental exposure
to ChE inhibitors.
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Organophosphate Insecticides-Cholinesterase Methods
1. Spectrophotometric:
Ellman Method
2. Electrometric:
Michel Method
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Organophosphate Insecticides- Principle of the modified electrometric method
Cholinesterase + Acetylcholine
Choline + Acetic acid
Decrease in pH
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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)
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Organophosphate Insecticides-Cholinesterase Activity (Delta pH)
Sheep Goats
Plasma 0.21 0.22
RBC 0.63 0.54Mohammad et al., 2005 (JAVA)
Man: Plasma (0.98), RBC (1.39)Mohammad et al., 2007 (J Med Toxicol)
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Organophosphate Insecticides-Cholinesterase Activity
Plasma vs. RBC
RBC ChE is preferred
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Organophosphate Insecticides-Cholinesterase inhibition
25% Exposure
50 – 75 % Poisoning cases
> 75% Serious
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Organophosphate Insecticides-ChE inhibiton (Mohammad et al., 2007-J Vet
Med A)
Sheep Goats Cattle0
10
20
30
40PChEEChE
% C
ho
lin
este
rase
in
hib
itio
n
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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).
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Organophosphate Insecticides-ChE for Biomonitoring
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Organophosphate Insecticides-ChE for Biomonitoring
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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??
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Organophosphate Insecticides-Drug interactions
Drugs to be avoided
Morphine Succinylcholine
Phenothiazines Barbiturates
Carbachol Physostigmine
Neostigmine Theophylline
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Thank You
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Questions??