11 – Insecticides Flashcards
Organochlorine insecticides
- Most have been banned for use in Canada and USA
- Environmentally persistent (bioaccumulation, bioconcentration, biomagnification)
- Modern poisonings are uncommon
- Ex. DDT, methoxychlor, lindane, etc.
Organochlorine insecticides: mechanism
- Interference with action potentials and NTs in the CNS
o DDT: interacts with Na and K influx/efflux
o GABA inhibition
o Enhanced acetylcholine release
o *CNS excitation
Organochlorine insecticides: toxicokinetics
- High lipophilicity
o Partition to fatty tissues: adipose, brain
o Excreted in milk - Very long elimination half life: months
o Enterohepatic recirculation
Organochlorine insecticides: onset
- Within hours of exposure
Organochlorine insecticides
- Behaviour: anxiety, agitation/aggression, jumping over invisible objects
- GI: vomiting, salivation
- CNS excitations: tremors, intermittent tonic-clonic seizures, opisthotonus, paddling, clamping
- Progression to coma and death
- No specific PM lesions
Organochlorine insecticides: management
- No specific antidote
- Decontamination if NOT contraindicated
o Dermal exposure: wash - Symptomatic and support care
o Anticonvulsants
o Mehthocarbamol
o Fluids, oxygen, mechanical ventilation
o Consider ILE, cholestryramine
Organochlorine insecticides: diagnosis
- Some labs have the pesticides screens: fat, liver, brain, gastric contents
Organochlorine insecticides: public health (one health)
- Long elimination half-life
- Human health
o Endocrine disruption
o Carcinogenicity - Residue concerns in food producing animals
Organochlorine insecticides: environment (one health)
- Persistent organic pollutants
- Negative impact on wildlife populations (thinning of egg shells)
- Decades
Organophosphate & Carbamate Insecticides
- Most common group of pesticides/insecticides used globally
o Not environmentally persistent, but still highly toxic - Chemically distinct group, but have the same mechanism
- Agricultural use, flea and tick treatments, shampoos, dips
- Exposure scenarios
o Malicious poisoning
o Accident;: access to chemicals, ingestion of cattle ear tags, spraying, treated crops
OP and carbamates: toxicity
- Varies between compounds and species
- More acutely toxic than OC insecticides
OP and carbamates: mechanism of action
- *inhibition of acetylcholinesterase
o ACh not broken down, so overstimulation of
Nicotinic ACh receptors
Muscarinic ACh receptors
OP vs. carbamates
- OP: irreversibly bind to AChE enzyme
o Enzyme aging: irreversible inactivation of AchE - Carbamates: reversible inhibition
o No enzyme aging
o Shorter half life of inhibition
o Shorter duration of clinical signs
OP and carbamates: acute toxicosis
- Route of exposure: ingestion, inhalation, dermal
- Onset: as early as 15 mins post-exposure
- 3 major categories of symptoms
OP and carbamates: acute toxicosis and muscarinic AChR overstimulation
- *rest and digest
- S: salivation
- L: lacrimation
- U: urination
- D: diarrhea
- G: GI cramping
- E: emesis
- **bradycardic
- Bronchorrhea
- Bronchospasm
- Miosis
- **USUALLY ARE THE ONES TO APPEAR FIRST=LIFE THREATENING
OP and carbamates: acute toxicosis and nicotinic AChR overstimulation
- Muscle fasciculations
- Tremors
- Weakness
- Ataxia
- Muscle stiffness
- Paralysis
OP and carbamates: acute toxicosis and CNS overstimulation
- Anxiety
- Restlessness
- Depression or hyperactivity
- Tonic-clonic seizures
- Respiratory depression coma
OP and carbamates: acute toxicosis, death is due to
- Bronchoconstriction/bronchorrhea
- Respiratory failure and hypoxia
OP and carbamates: acute toxicosis and PM lesions and clinical pathology
- PM: Congestion, edema, hemorrhage
- May observe insecticide granules in stomach/rumen contents if oral exposure
- Check gastric contents for anything that resembles bait
- No regular clin path tests
OP and carbamates: intermediate syndrome
- Reported in dogs and cats
- Onset: 24-96hrs after acute cholinergic crisis
- Predominance of NICOTINIC SIGNS
o Clinical pathology: decreased AChE activity
OP and carbamates: OP-induced delayed polyneuropathy (OPIDPN) (carbamates as well)
- Due to degeneration of long motor nerves via inhibition of neuropathy target esterase
- 1-4 weeks after exposure to an OP
- Ataxia, pelvic limb weakness
- Clinical pathology: NORMAL blood AChE
OP and carbamates: acute toxicosis, antidote
- *ATROPINE (muscarinic receptor antagonist)
o Control of bradycardia and bronchial secretions - If KNOWN OP/carbamate exposure: small, then loading dose, then follow up
- Can also do for classic cholinergic toxidrome with UNKNOWN exposure
- SUGGESTIVE cholinergic toxidrome, but no history of exposure
o Test dose of atropine (b/c do NOT want to overdose on atropine)
- SUGGESTIVE cholinergic toxidrome, but no history of exposure
OP and carbamates: supportive care
- Oxygen, mechanical ventilation
- Fluids
- Seizure control
- Anti-emetics
OP and carbamates: intermediate syndrome management
- NO atropine indicated
o Why? Nicotinic signs, so atropine would NOT help - 2-PAM
- *Supportive care
- Slow recovery (weeks)
OP and carbamates: OP-induced delayed polyneuropathy (OPIDPN), management
- NO atropine indicated
o Why? Nicotinic signs, so atropine would NOT help - Supportive care
OP and carbamates: acute toxicosis and intermediate syndrome, diagnosis
- History (SLUDGE signs)
- Response to atropine
- **Antemortem: AChE activity of heparinized whole blood
o If less than 50% of normal: suspicious
o If less than 25% of normal: diagnostic - *PM: BRAIN AChE activity
- Analysis of stomach contents, urine, other tissues with pesticide screen
OP and carbamates: OPIDN, diagnosis
- History of acticholinesterase exposure
- NTE test: not available at diagnostic labs
- NO specific gross lesion
- Histo of nerves: Wallerian degeneration
