This ppt tells about OPI poisoning in animals. Insecticide poisoning is a serious issue in Veterinary practice. This ppt tries to cover in detail all aspects of OP insecticide poisoning in animals.

1. ORGANOPHOSPHOROUS
INSECTICIDES
ORGANIC ESTERS OF PHOSPHOROUS
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2. • The first OP compound synthesized in 1854 by Philipe de Clermont was
tetraethyl pyrophosphate
• Gerhard Schrader led the exploration of OP compounds that could be used as
insecticides
• One of the earliest OP insecticides synthesized by Schrader was Parathion
• After WWII, thousands of OPs have been synthesized in the search for
compounds with species selectivity, i.e. more toxic to insects and less toxic to
mammals (malathion)
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3. USES
• INSECTICIDES & INSECTICIDE
SYNERGISTS
• ACARICIDES & RODENTICIDES
• SOIL NEMATICIDES
• FUNGICIDES & HERBICIDES
• DEFOLIANTS
• INSECT REPELLANTS
• CHEMOSTERILANTS
• WAR FARE AGENTS
GENERAL FORMULA
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4. •All OP compounds have a pentavalent phosphorus atom & a characteristic
phosphoryl bond (P=O) or thiophosphoryl bond (P=S)
•OP compounds have two alkyl substituents and a leaving group, which is
more labile to hydrolysis than the alkyl group
•OPs are esters of phosphoric acid with varying combinations of O, C, S or
N
•OPs that are derivatives of phosphoric or phosphonic acid possess anti-
AChE activity, unlike derivatives of phosphinic acid
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5. •Some OPs (such as dichlorvos, monocrotophos, & trichlorfon) are direct
AChE inhibitors
•Those of phosphorothioates type (such as bromophos, diazinon,
fenthion, & parathion) possess minimal or no anti-AChE & require
desulfuration to the analogous oxon before acquiring anti-AChE activity
•OPs which are used as defoliants (s,s,s-tributyl phosphorotrithioate &
s,s,s-tributyl phosphorotrithioite) & herbicides (glyphosate &
gluphosinate) are of very low mammalian toxicity
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6. CLASSIFICATION BASED ON CHEMICAL STRUCTURE
•PHOSPHATES AND PYROPHOSPHATES: Paraoxon, Tetraethyl
Pyrophosphate (TEPP), Schraden, Dichlorvos
•PHOSPHOROTHIOATES: Parathion, Fenthion, Diazinon,ronnel
•PHOSPHONATES:Trichlorfon
•PHOSPHORAMIDATES: Phospholan, Mephospholan
•PHOSPHOROTHIOLATES: Echothiophate, Profenphos
•PHOSPHOROHALIDES: Diisopropyl Fluorophosphate (DFP), Sarin
•PHOSPHOROCYANIDES: Tabun
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7. CLASSIFICATION (BASED ON STRUCTURE)
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8. DIRECT ACTING
•Contain P=O
•Directly inhibit AChE
•TEPP, dichlorvos, trichlorfon
INDIRECT ACTING
•Phosphorothioates (P=S)
•Inactive anti-AChE
•Require activation to oxons
•Malathion, parathion,
fenthion
CLASSIFICATION (BASED ON MODE OF
ACTION)
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9. FACTORS AFFECTING TOXICITY
Compound
Storage- contamination, heat induced isomerisation & pH changes
Ambient temperature
Species
Age
Interaction
Formulation
Impurities
Other factors
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10. TOXICOKINETICS
•Gain entry into the body mainly through oral, dermal, or inhalation
•Lipid soluble, so absorbed from all body surfaces; do not accumulate in
any particular tissue
•Well distributed in tissue throughout the body
•May follow either activation or detoxification, or both
•Some transformed to quaternary compounds- cannot enter brain
(phosphoroamidates)
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11. •In liver esterases convert OP compounds to water soluble
metabolites- rapidly excreted in urine
•Hydrolysis of ester linkage markedly reduces its toxicity
•Chlorinated Ops are more lipid soluble & residues persist for
long time
•Residues are detected in the feces, saliva & milk
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12. MECHANISM OF ACTION
• Inhibit the enzyme AChE within nerve tissue & at the neuromuscular
junctions
• ChE are serine hydrolases that catalyze the breakdown of ACh through an
acyl-transfer, where water is the acceptor molecule to which the substrate acyl
moiety is transferred
• A serine O of the active site of ChEs carries out a nucleophilic attack on the
electrophilic C of the carbonyl group of ACh, resulting in an acetylated enzyme
intermediate & release of choline
• Deacetylation occurs when an attacking water molecule (hydroxyl ion) acts as
a more effective nucleophile, thereby releasing acetate
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13. 13

14. 14

15. 15

16. •Interact only with the esteratic site of AChE
•The complex formed is very stable as it doesn’t undergo
rapid hydrolysis
•Restoration of AChE synthesis of new enzyme
several weeks
•Also inhibit butyryl choline esterse & neurotoxic
esterase
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17. • Binding of AChE by different OPs
varies in affinity and reversibility
• After binding, the enzyme is
‘phosphorylated’, and thus
inhibited & is regarded as
‘irreversible’
• Irreversible inhibition of AChE
causes accumulation of ACh in the
neuromuscular junction,
parasympathetic postganglionic
terminals in smooth muscles,
cardiac muscle & glands
PHOSPH
ORYLAT
ION
REACTI
VATION
AGING
REGENE
RATION
4 STAGES OF AChE
INHIBITION
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18. 18

19. CLINICAL SIGNS
MUSCARINIC SIGNS
•Profuse salivation & sweating
• Lacrimation & pupil constriction
• Serous or seromucous nasal
discharge, bradycardia
•Increased respiratory sounds
due to bronchoconstriction &
excess bronchial secretions,
coughing
•Pronounced gastrointestinal
sounds, colic and diarrhoea due
to increased gastrointestinal
motility
•Vomiting & frequent urination
NICOTINIC SIGNS
•Muscle fasciculation
• Tremors
•Twitching
•Spasm &
hypertonicity causing
a stiff gait or rigid
stance
CNS EFFECTS
•Effects vary with species
•Severe CNS depression
•Anxiety, restlessness &
hyperactivity death due to
respiratory failure,
•Bronchoconstriction
&convulsions may be life
threatening
SLUDD SYNDROME 19

20. •Mechanism of action is not very clear
•Not due to anti-AChE activity
•Polyneuritis, demyelination, sensory disturbances, muscle weakness,
tenderness, depressed tendon reflexes, lower and upper motor neuron
paralysis
CHRONIC OP POISONING
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21. OPIDN/OPIDP
• Esters of phosphorus-containing acids produce delayed neurotoxic effects
• Tri-o-cresyl phosphate (TOCP) was known to produce delayed neurotoxic effects in
man and chicken, characterized by ataxia and weakness of the limbs, developing 10–
14 days after exposure- OPIDN
• Renamed as OPIDP now
• OPIDP is characterized by distal degeneration of long- and large diameter motor &
sensory axons of both peripheral nerves &spinal cord
• Among all animal species hen appears to be the most sensitive & used as an animal
model
• TOCP and certain other compounds have minimal or no anti-AChE property, however
they cause phosphorylation & aging of a protein in neurons called neuropathy target
esterase (NTE) leading to OPIDP
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22. Post mortem findings
•Non specific
•Pulmonary edema,
congestion,
•Coagulative necrosis in liver,
cerebral edema
•Patches of necrosis in
skeletal muscle
•Intestinal tract may be
dilated & filled with fluid
Diagnosis
•History
•Clinical signs
•Estimation of
AChE in blood &
tissues
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23. TREATMENT
•Combined use of atropine sulfate and pyridine-2- aldoxime
methochloride (2-PAM)
•Before instituting antidotal therapy, monogastric animals, such as dog,
should be given gastric lavage
•Animals of any species can be given activated charcoal to stop further
absorption of insecticides
•Animals should be washed thoroughly with water if they are exposed to
insecticides dermally
•Intravenous (iv) fluid therapy is always beneficial
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24. •Oxygen therapy if cyanosis & dyspnoea are prominent
•Washing the animal with plenty of water & detergent
• Administration of mineral oil
• Keeping the animal quiet & comfortable
CONTRAINDICATIONS
Neuromuscular blocking Drugs
Anesthetics
Atropine in cyanotic cats
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