1. Organophosphate Poisoning in Sheep Fouad K. Mohammad College of Veterinary Medicine University of Mosul, Iraq 2007

2. Organophosphate Insecticides- Structure Derivatives of phosphoric acid:

3. Organophosphate Insecticides- Examples Bromophos Coumaphos Crotoxyphos Diazinon Dichlorvos Malathion

4. Organophosphate Insecticides-Uses Ectoparasicides: Dips, Sprays, Pour-on, Dusting

5. Organophosphate Insecticides-Dip

6. Organophosphate Insecticides- Absorption Oral Dermal Inhalational

7. Organophosphate Insecticides- Toxicity LD50 (lab animals) varies widely 1-3 mg/kg for parathion to 1375 mg/kg for malathion

8. Organophosphate Insecticides- Mechanism of ChE action

9. Organophosphate Insecticides- Mechanism of toxic action

10. OP + ChE  IrreversibleInhibition!!  Ach accumulation at nerve terminals

11. Organophosphate Insecticides- Signs of poisoning Muscarinic Nicotinic CNS effects

12. Organophosphate Insecticides- Signs of poisoning Muscarinic: Salivation, Lacrimation, Bronchoconstriction, Urination, Increase GIT motility

13. Organophosphate Insecticides- Signs of poisoning Nicotinic: Muscle tremors, Ataxia, Generalized tetany, Weakness and Paresis

14. Organophosphate Insecticides- Signs of poisoning-Nicotinic

15. Organophosphate Insecticides- Signs of poisoning-Depression

16. Organophosphate Insecticides- Causes of Death Respiratory Depression Bronchconstriction Excessive excretions in the resp. tract Depression of Medulla

17. Organophosphate Insecticides- Lesions Non-specific: pulmonary edema, blanched mucous membranes, petecheal hemorrhages, increased fluid in the GI tract and increased flaccidity of the intestines.

18. Organophosphate Insecticides- Lesions

20. Organophosphate Insecticides- Diagnosis History ChE Activity in Blood & Tissue Chemical Analysis of tissues Atropine treatment (0.02 mg/kg, iv)

21. Organophosphate Insecticides- Cholinesterase True Cholinesterase (Brain, RBC) Pseudo Cholinesterase (Plasma, Liver)

22. Organophosphate Insecticides- Cholinesterase importance 1. Diagnosis of poisoning with ChE inhibitors. 2. Monitoring exposure to ChE inhibitors. 3. Monitoring environmental exposure to ChE inhibitors.

23. Organophosphate Insecticides- Cholinesterase Methods 1. Spectrophotometric: Ellman Method 2. Electrometric: Michel Method

24. Organophosphate Insecticides- Principle of the modified electrometric method Cholinesterase + Acetylcholine Choline + Acetic acid Decrease in pH

25. 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)

26. 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)

27. Organophosphate Insecticides- Cholinesterase Activity Plasma vs. RBC RBC ChE is preferred

28. Organophosphate Insecticides- Cholinesterase inhibition 25% Exposure 50 – 75 % Poisoning cases > 75% Serious

29. Organophosphate Insecticides- ChE inhibiton (Mohammad et al., 2007-J Vet Med A)

30. 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).

31. Organophosphate Insecticides- ChE for Biomonitoring

33. 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??

34. Organophosphate Insecticides- Drug interactions Drugs to be avoided Morphine Succinylcholine Phenothiazines Barbiturates Carbachol Physostigmine Neostigmine Theophylline

35. Thank You

36. Questions??