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??