11 – Insecticides

Question 1

Organochlorine insecticides

Answer 1

• Most have been banned for use in Canada and USA
• Environmentally persistent (bioaccumulation, bioconcentration, biomagnification)
• Modern poisonings are uncommon
• Ex. DDT, methoxychlor, lindane, etc.

Question 2

Organochlorine insecticides: mechanism

Answer 2

• 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

Question 3

Organochlorine insecticides: toxicokinetics

Answer 3

• High lipophilicity
  o Partition to fatty tissues: adipose, brain
  o Excreted in milk
• Very long elimination half life: months
  o Enterohepatic recirculation

Question 4

Organochlorine insecticides: onset

Answer 4

• Within hours of exposure

Question 5

Organochlorine insecticides clinical signs

Answer 5

• 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

Question 6

Organochlorine insecticides: management

Answer 6

• 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

Question 7

Organochlorine insecticides: diagnosis

Answer 7

• Some labs have the pesticides screens: fat, liver, brain, gastric contents

Question 8

Organochlorine insecticides: public health (one health)

Answer 8

• Long elimination half-life
• Human health
  o Endocrine disruption
  o Carcinogenicity
• Residue concerns in food producing animals

Question 9

Organochlorine insecticides: environment (one health)

Answer 9

• Persistent organic pollutants
• Negative impact on wildlife populations (thinning of egg shells)
• Decades

Question 10

Organophosphate & Carbamate Insecticides

Answer 10

• 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

Question 11

OP and carbamates: toxicity

Answer 11

• Varies between compounds and species
• More acutely toxic than OC insecticides

Question 12

OP and carbamates: mechanism of action

Answer 12

• *inhibition of acetylcholinesterase
  o ACh not broken down, so overstimulation of
   Nicotinic ACh receptors
   Muscarinic ACh receptors

Question 13

OP vs. carbamates

Answer 13

• 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

Question 14

OP and carbamates: acute toxicosis

Answer 14

• Route of exposure: ingestion, inhalation, dermal
• Onset: as early as 15 mins post-exposure
• 3 major categories of symptoms

Question 15

OP and carbamates: acute toxicosis and muscarinic AChR overstimulation

Answer 15

• *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

Question 16

OP and carbamates: acute toxicosis and nicotinic AChR overstimulation

Answer 16

• Muscle fasciculations
• Tremors
• Weakness
• Ataxia
• Muscle stiffness
• Paralysis

Question 17

OP and carbamates: acute toxicosis and CNS overstimulation

Answer 17

• Anxiety
• Restlessness
• Depression or hyperactivity
• Tonic-clonic seizures
• Respiratory depression coma

Question 18

OP and carbamates: acute toxicosis, death is due to

Answer 18

• Bronchoconstriction/bronchorrhea
• Respiratory failure and hypoxia

Question 19

OP and carbamates: acute toxicosis and PM lesions and clinical pathology

Answer 19

• 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

Question 20

OP and carbamates: intermediate syndrome

Answer 20

• Reported in dogs and cats
• Onset: 24-96hrs after acute cholinergic crisis
• Predominance of NICOTINIC SIGNS
  o Clinical pathology: decreased AChE activity

Question 21

OP and carbamates: OP-induced delayed polyneuropathy (OPIDPN) (carbamates as well)

Answer 21

• 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

Question 22

OP and carbamates: acute toxicosis, antidote

Answer 22

• *ATROPINE (muscarinic receptor antagonist)
  o Control of bradycardia and bronchial secretions
• 1. If KNOWN OP/carbamate exposure: small, then loading dose, then follow up
• 2. Can also do for classic cholinergic toxidrome with UNKNOWN exposure
• 3. SUGGESTIVE cholinergic toxidrome, but no history of exposure
     o Test dose of atropine (b/c do NOT want to overdose on atropine)

Question 23

OP and carbamates: supportive care

Answer 23

• Oxygen, mechanical ventilation
• Fluids
• Seizure control
• Anti-emetics

Question 24

OP and carbamates: intermediate syndrome management

Answer 24

• NO atropine indicated
  o Why? Nicotinic signs, so atropine would NOT help
• 2-PAM
• *Supportive care
• Slow recovery (weeks)

Question 25

OP and carbamates: OP-induced delayed polyneuropathy (OPIDPN), management

Answer 25

- NO atropine indicated o Why? Nicotinic signs, so atropine would NOT help - Supportive care

Question 26

OP and carbamates: acute toxicosis and intermediate syndrome, diagnosis

Answer 26

- 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

Question 27

OP and carbamates: OPIDN, diagnosis

Answer 27

- History of acticholinesterase exposure - NTE test: not available at diagnostic labs - NO specific gross lesion - Histo of nerves: Wallerian degeneration