Organophosphate Poisoning in Sheep Fouad K. Mohammad College of Veterinary Medicine University of...
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Transcript of Organophosphate Poisoning in Sheep Fouad K. Mohammad College of Veterinary Medicine University of...
Organophosphate Poisoning in Sheep
Fouad K. MohammadCollege of Veterinary Medicine
University of Mosul, Iraq2007
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
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 DepressionBronchconstriction
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-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
+
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 0.54Mohammad 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)
Sheep Goats Cattle0
10
20
30
40PChEEChE
% C
ho
lin
este
rase
in
hib
itio
n
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-ChE for Biomonitoring
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
Thank You
Questions??