Antiesterases

• ORGANOPHOSPHATES
• CARBAMATES
Lecture Outline
At the end of this lecture, the student
will be able to:
List the categories of anti-esterase
neuro-toxicants and their sources
Describe the clinical signs,
mechanism of toxic action, diagnosis
and management of anti-esterase
poisoning
Anticholinesterase Insecticides

• Organophosphates
• Carbamates
– Variable toxicity
– Toxicity usually occurs from misuse of
products or improper storage
 Organophosphate & Carbamate
Insecticides
 OPs are ester derivatives of phosphoric
acid (PO4)
 Carbamates are esters of carbamic acid
 lipophilic compounds
 Some OPs are protoxicants, must be
activated by P450
 unstable, hydrolyze rapidly in environment
 detoxified by hydrolysis - chemical or
esterase
 Sources of Antiesterase
Insecticides
 used on crops, stored grain, soil, structures,
 animals - treat insect/nematode infestation
 flea collars
higher concentrations approved for dogs
than cats
 fly, ant, roach baits
 veterinary drugs - antihelmintics,
ophthalmics
 nerve gas, industrial plasticizers and
lubricants
Potential Problem
OP Nomenclature
 OP/Carbamate Toxicity
 fenthion (ProSpot) - 220 mg/kg
 cythioate (ProBan) - 160
 dichlorvos (Task) - 56
 trichlorfon (Combot) - 600
 chlorpyrifos (Dursban)- 145
 carbaryl (Sevin) - 250
 aldicarb (Temik) -1
 carbofuran (Furadan) - 2
 Physostigmine - 4.5
 Types of Esterases
 Acetylcholinesterase-true cholinesterase
 inhibition responsible for acute toxicity
 found in nervous tissue and erythrocytes
 Pseudocholinesterase
(butyrylcholinesterase)
 also inhibited by OP/carbamate, protect AChE
 non-neural tissues (liver, serum)
 Aliesterases (A-esterases)
 not inhibited by OP/carbamate
 missing in birds
 Esterases cont’d
• Carboxylesterases
• metabolize local anaesthetics, OPs, atropine
• neural and non-neural
• inhibition not correlated with acute toxicity
• Neurotoxic esterases (NTE)
• delayed neuropathy
Mechanism of Action

Inhibition of acetylcholinesterase
 Summary of MOTA
Inhibition of AChE
ACh accumulates = excessive
synaptic neurotransmitter activity in
PNS and at neuromuscular (nicotinic)
sites
reversible binding = carbamates
irreversible binding (aging) = varies
with specific OP involved
 Signs of Antiesterase Toxicity
 Muscarinic
Salivation, lacrimation, urination,
diarrhea, miosis, dyspnea, bradycardia
 Nicotinic
Muscle fasciculations beginning with
face, generalized tremors, weakness
 CNS
Respiratory depression, clonic-tonic
seizures
 Signs … … cont’d
• Muscarinic
• Salivation, lacrimation, urination, diarrhea, miosis,
dyspnea, bradycardia
• Nicotinic
• Muscle fasciculations beginning with face,
generalized tremors, weakness
• CNS
• Respiratory depression, clonic-tonic seizures
• Rumen stasis in cattle, but not miosis
• Signs may last 1-5 days
Diagnosing Anticholinesterase Toxicity
 Appropriate history and clinical signs
 Atropine test dose - (0.01-0.05 mg/kg),
wait 15 min to observe for dry mouth,
mydriasis, normal extent and duration of
rapid heart beat - if observed toxicity not
due to cholinesterase inhibitor
 AChE activity
 Chemical analysis
 Non-specific pathology; may see pulmonary
oedema and petechial haemorrhage in GI
mucosa
Treatment of Anti-Esterase Toxicity
 GI decontamination
 Atropine sulphate for muscarinc signs,
dose to effect; will not stop nicotinic
signs
 Oximes (protopam) can reactivate AChE
before aging; if no improvement after 4
doses, discontinue
 Diazepam or barbiturates for seizures
 Time
 Excellent prognosis
 Considerations with OPs and/or
carbamates
Birds are very susceptible to OP
poisoning (diazinon and ducks)
In cats, dermal=oral; chlorpyrifos
causes more nicotinic signs in cats
due to muscarinic tolerance
Brahman bulls with chlorpyrifos
Vehicle (kerosene)
 OPIDN

OP compounds that produce

significant inhibition of NTE may
cause delayed neuropathy
 Characterized by axonal
degeneration of long motor neurons
Hind limb weakness, paralysis
No treatment
Summary
1. Variable toxicity – dose & species
2. Varied sources – insect infestation,
flea collars, baits, veterinary drugs,
industry, chemical warfare
3. Inhibition of esterases esp. AChE
4. Clinical signs - OPIDN
5. (Antidotal) treatment
THE END
QUESTIONS ?