4.5 Insecticides and Rodenticides

Question 1

are most herbicides, pesticides, insecticides and fungicides very toxic? what is the prognosis? are there exceptions?

Answer 1

• most herbicides, pesticides, insecticides and fungicides have low toxicity and high success rate of treatment
• Exceptions include organophosphate/carbamate insecticides and rodenticides= these are extremely toxic

Question 2

what is rotenone? what is it used for? what species is it toxic for? what is the mechanism of toxicity?

Answer 2

Source/Exposure: topical treatment of cattle lice and mites, flea control products (less common),
 Excessive use of powders and dips: i.e. cats, grooming & oral exposure
 Intentionally in water to kill fish – easily absorbed through gills

Toxicity:
 birds, fish and cats are most susceptible
 acute toxicity most common

Mechanisms of Toxicity:
 Physical irritant
 Interferes with nerve conduction (blocks mitochondrial electron transport chain)

Question 3

clinical signs of rotenone toxicity?

Answer 3

vomiting (low dose) but may progress to lethargy, tremors, seizures (high dose) ➝ respiratory failure, dyspnea and death

Question 4

how do we diagnose rotenone toxicity?

Answer 4

history, pulmonary congestion, GI irritation

Question 5

how do we treat rotenone toxicity? what is the prognosis?

Answer 5

 Treatment:
-minimize absorption: bathe with detergent; nonspecific detoxification
-correct acidosis if present
-diazepam for seizures
 Prognosis: good

Question 6

what are pyrethrins/pyrethroids? what are they used for? what is their toxicokinetics and mechanism of toxicity?

Answer 6

Source/Exposure: insecticides & flea control
 Excessive use of sprays or spot-on products
 Inappropriate use (enclosed spaces, open aquariums)

Toxicokinetics:
 Lipophilic, partially absorbed orally and dermally  Distributed to high lipid tissues (fat, CNS, PNS)
 Rapidly metabolized & excreted

Mechanism of Toxicity:
 Binds to sodium channel on nerves > Prolonged opening of Na+ channels ➝ repetitive sensory nerve impulses

Question 7

clinical signs of pyrethrin/pyrethroid toxicosis?

Answer 7

 Paresthesia, abnormal behaviour
 Irritation: Salivation, vomiting, diarrhea
 Hyperexcitability, tremors & seizures,
dyspnea, weakness & death
 Highly toxic to cats and fish

Question 8

how can we diagnose pyrethrin/pyrethroid toxicosis?

Answer 8

History; no specific clinical or anatomic pathology lesions; tissue analysis not useful

• CBC: stress leukogram
• biochemistry: hyperglycemia
• R/O: Organophosphates, metaldehyde

Question 9

treatment for pyrethrin/pyrethroid toxicity? prognosis?

Answer 9

 Treatment: no antidote, try to minimize absorption: bathe with detergent, general detoxification, and control seizures/spasms: diazepam, barbiturates, methocarbamol
 Prognosis: generally excellent (cats with spot-on, guarded)

Question 10

how would a cat with pyrethrin toxicity look at on presentatoin? what is the mechanism that results in this?

Answer 10

Binds to sodium channel on nerves
> Prolonged opening of Na+ channels ➝ repetitive sensory nerve impulses

Question 11

what is the source of organophosphates and organocarbamates? what are they used for and how can animals be exposed?

Answer 11

Source/Exposure: still widely used
 Insecticides: fly, ant & roach baits, shampoos, collars, dips & sprays
 Animals can be exposed by contaminated feedstuffs
 Improper use: plant insecticides on animals

Question 12

what are the toxicokinetics of organophosphates and organocarbamates?

Answer 12

Toxicokinetics:
 Rapidly absorbed *by any route
 Do not accumulate in fat
 Metabolized by plasma esterases
 Rapidly excreted in urine

Question 13

Mechansim of toxicity of organophosphates and organocarbamates?

Answer 13

 Phosphorylates or carbamylates bind acetycholinesterase (AChE) to inhibit it
> Remember – AChE plays a vital role in the breakdown of the neurotransmitter acetylcholine, which is found in both the peripheral and central nervous systems
> Increased ACh in cholinergic synapses at parasympathetic (muscarinic) & neuromuscular (nicotinic) sites
>neurons continue to fire

 OP have higher affinity for AChE than do carbamates
 OPs have a reversible bond until “aging” (loss of one of alkyl groups) occurs, then stable bond and irreversible
 OCs are reversible/temporarily bound to AchE

Question 14

what is the nature of of the toxicity of organophosphates and organocarbamates? what species are susceptible? how long does it take for effects to leave?

Answer 14

 High acute toxicity, rarely chronic
 Cats more susceptible than dogs
 Poultry have lower tolerance than mammals
 Metabolized & excreted rapidly, AChE regeneration needs 2 wks

Question 15

clinical signs of toxicity due to organophosphates and organocarbamates

Answer 15

Muscarinic & nicotinic signs; excessive cholinergic stimulation
Acute poisoning can occurs within 30 min, usually 6h
These mnemonic devices can help you remember the signs of organophosphate toxicities (most of these are due to muscarinic overstimulation):
SLUDGE

Question 16

how do we diagnose organophosphates and organocarbamates toxicity? should we wait for results to treat? what type of sample can be useful to look at after some time has passed?

Answer 16

 Evaluation of cholinesterase activity suggestive of exposure
> Remember these compounds phosphorylate or carbamylate acetycholinesterase (AChE) to inhibit it, so activity should be REDUCED

 Whole blood (EDTA; cattle), plasma (dogs) or brain
> Also can test urine, hair, GI contents
> Depression of blood cholinesterase does not necessarily correlate with the severity of poisoning, but can help make the diagnosis

 Don’t wait for results, treat immediately
 If storage necessary, freeze plasma
 Decreased blood AChE activity by 25-50% in severe cases
 Tissue residues low since not stored i.e. OPs hydrolyzed within hrs, stomach contents useful

Question 17

how do we treat a case of organophosphates and organocarbamates toxicity? what is the prognosis?

Answer 17

• Decontamination: bathe, emesis, lavage, activated charcoal (esp in cattle)
• Treat seizures (usually with diazepam)
• Atropine (0.2-0.5 mg/kg) 1/4 IV, 3/4 SC repeat in 6h if necessary
• Pralidoxime chloride (2-PAM) 20 mg/kg IM, releases the AChE so it becomes functional again, if OP bonds have not aged (best case scenario given within 24 h!!!)
  > Aging of OP increases stability of phosphorylated enzyme and then 2-PAM not effective

Prognosis: very poor, high mortality
-early treatment and minimal exposure improves prognosis
-carbamates have better prognosis (bind less tightly to AChE)

Question 18

public health considerations for organophosphates and organocarbamates?

Answer 18

-Avoid exposure when washing/bathing
-Meat residues are not a problem since they are rapidly excreted
-Hold milk until no residues present

Question 19

what is metaldehyde used for? what animals ingest it more commonly?

Answer 19

Sources/Exposure: slug & snail bait
 Used in coastal/lowland wet areas
 Pets are attracted to baits
 Common in dogs, also in cats & sheep

Question 20

toxicokinetics of acetaldehyde?

Answer 20

 Acetaldehyde liberated by gastric acid
 Odor like mild formaldehyde
 Both metaldehyde and acetaldehyde are readily absorbed from the GI tract

Question 21

mechanism of metaldehyde

Answer 21

– Role of both metaldehyde and acetaldehyde is unclear,
may be due to decreased [serotonin] & [GABA] in brain

Question 22

clinical signs of metaldehyde toxicity?

Answer 22

ClinicalSigns: “Shake and Bake”
– All species susceptible, dogs most frequently affected
– Acute toxicity: anxiety, restlessness, ataxia
– Hypersalivation, mydriasis, tremors, ataxia, incoordination
– Severe muscle tremours, opisthotonos, convulsions, hyperthermia (all usually develop within 1–3 hr after ingestion)

Question 23

diagnosis of metaldehyde toxicity?

Answer 23

– No specific lesions
– Acetaldehyde in stomach (odour), submit contents frozen
– Test blood cholinesterase to R/O OP toxicosis
– Acidosis due to acetaldehyde production

Question 24

treatment of metaldehyde toxicity? prognosis?

Answer 24

Treatment:
 Emesis (if asymptomatic) or gastric lavage
 Activated charcoal to reduce enterohepatic cycling of metaldehyde.
 Seizure control: diazepam most commonly used
 IV fluids
 Sodium bicarbonate to reverse acidosis
 Monitor temp and cool with wet towels and fans
 No specific antidote

Prognosis:
 Depends on dosage, time elapsed, speed of treatment
 Good with aggressive treatment and supportive care

Question 25

what is amitraz? how are animals exposed to it?

Answer 25

Formamidine insecticide (Mitaban for demodecosis; Preventic, tick-repellent collars)

Source/Exposure:
 Topical miticide; flea collars, ectoparasite control in
swine
 Careless use of spray or dip
 Dogs may eat flea collars
 Contraindicated in horses

Question 26

toxicokinetics of amitraz

Answer 26

 Readily absorbed orally
 Excreted in urine

Question 27

mechanism of action of amitraz? what is the antidote?

Answer 27

Most of the adverse effects in mammals is related to alpha2 agonist effects in CNS (yohimbine or atipamezole reverses) < antidote!

Question 28

clinical signs of amitraz toxicity. how fast do they come on?

Answer 28

– Signs within 2-4h of exposure
– Bradycardia, sedation, hypotension (α2 effect), ataxia, depression, vomiting, diarrhea, seizures
– Horses are very susceptible to ileus and colic

Question 29

how to diagnose amitraz toxicity?

Answer 29

– Hyperglycemia, few specific lesions, amitraz in stomach contents

Question 30

how to treat amitraz toxicity? prognosis?

Answer 30

– Detoxification: bathe, emetics (early), activated charcoal
– Yohimbine/atipamezole to treat α2 effects
– IV fluids, diazepam for seizures

prognosis:
– Good with prompt and appropriate Rx

Question 31

what are macrolide endectocides? what is their mechanism?

Answer 31

 Source: Ivermectin (Ivomec, Heartgard, Eqvalan), abamectin, dormectin (Dectomax), milbemycin oxime (Interceptor), moxidectin (ProHeart, Quest), selamectin (Revolution)

 Mechanism: GABA agonist (GABA in CNS in mammals)
-GABA found in PNS in arthropods & nematodes

Question 32

what is the toxicity of macrolide endectocides? what animals are susceptible?

Answer 32

 Very safe in most breeds of dog (toxicity at 200x Rx dose)
 Collies, shelties & border collies are most susceptible (15x Rx dose)
 Collies have a mutation in mdr gene that codes for a P-glycoprotein drug efflux protein in the blood-brain barrier – inhibits ability to restrict entry ivermectin into brain

Question 33

clinical signs of macrolide endectocide toxicity

Answer 33

 Tremors, mydriasis, depression, ataxia, coma & death

Question 34

treatment of macrolide endectocide toxicity? prognosis?

Answer 34

Treatment:
 Decontamination: charcoal & cathartic if recent oral exposure
 Supportive care
 Epinephrine for acute anaphylactic reactions

Prognosis: therapy may be prolonged but prognosis good

Question 35

what is fipronil and what does it cause? how can we treat toxicity and what is the prognosis?

Answer 35

Fipronil (Frontline) -spot-on & spray (binds GABA gated Cl channels)
-Dermal hypersensitivity reactions;
-Tremors/seizures in rabbits (off-label)
-Bathe with detergent; diazepam for seizures
-Prognosis good for most exposures; guarded for seizing rabbits

Question 36

what is imidacloprid and what does it do? what can it cause in toxic doses and how do we treat?

Answer 36

Imidacloprid (Advantage) -spot-on
-ACh receptor agonist; higher affinity for insect receptors
-Acute oral toxicity: salivation or vomiting
-Dermal hypersensitivity –bathe with detergent
-Antihistamines or steroids in extreme cases

Question 37

what is 4-aminopyridine (Avitrol)? what is it used for?

Answer 37

Avicide

• Sources:
  – Bird control agent, usually in corn
  – Bait has 0.5-3.0% 4-aminopyridine
  – Pigeons or starlings often presented
  – Abnormal behaviour; distress cry
  – Intent is to poison a few, frighten the rest away
  – Infrequently ingested by dogs and horses

Question 38

toxicokinetics of 4-aminopyridine (Avitrol)

Answer 38

– Rapidly absorbed by GIT
– Rapid hepatic metabolism, excreted in urine

Question 39

mechanism of action of avitrol

Answer 39

– Increased release of ACh ➝ increased cholinergic neurotransmission
– Blocks K+ current of repolarization
– Resembles toxicity by cholinesterase inhibitors

Question 40

what is avitrol toxic for?

Answer 40

– Highly toxic to birds and mammals
– LD50 of 3.7 mg/kg (dogs)
– i.e. LD50 dose for 25 kg dog = 20 g of 0.5% bait

Question 41

clinical signs of 4-aminopyridine (Avitrol) toxicity?

Answer 41

Mammals:
– Nervous system overstimulation (like OPs):
> Hyperexcitability, salivation, tremors, incoordination, tonic clonic seizures
– Cardiac arrhythmias, tachycardia (unlike OPs)

Birds:
– Disorientation, seizures, vocalization

Question 42

how can we diagnose 4-aminopyridine (Avitrol) toxicity?

Answer 42

Ddx: OP insecticides, metaldehyde, tremorgenic mycotoxins No specific pathology lesions; 4-AP in stomach, liver, kidney

Question 43

treatment for 4-aminopyridine (Avitrol) toxicity? prognosis?

Answer 43

– Detoxification, before signs
– Pancuronium bromide (neuromuscular blocker) as antagonist
– Diazepam for seizures

• Prognosis
  – Favourable if survive 4h after onset of signs