pyrethrins/pyrethroids

Question 1

How are pyrethrin/pyrethroids used?

Answer 1

• home and farm insecticide
• farm animals
• companion animals (fleas/ticks)

most cannot be used on cats

Question 2

what is the relationship between pyrethrins and pyrethroids?

Answer 2

pyrethroids are synthetic analogs of pyrethrins

• pyrethroids now make up the majority of commercial household insecticides (like BOP)

Question 3

are pyrethrins water or lipid soluble?

Answer 3

lipid

Question 4

so synthetic pyrethroids or natural pyrethrins have higher risk for acute toxicity?

Answer 4

natural pyrethrins

Question 5

how does an animal get a chronic toxicity to pyrethrins?

Answer 5

respiration mainly, less by dermal

Question 6

What are the different toxicity levels with pyrethrins?

Answer 6

• high toxicity in bees
• high acute toxicity in fish and aquatic invertebrates
• high acute toxicity in cats

Question 7

which generation of pyrethroids are more toxic?

Answer 7

second generation (type 2) - do not contain alpha-cyano moiety which increases insecticidal potency and decreases metabolism

Question 8

what are the toxicokinetics of pyrethroids?

Answer 8

• more lipophilic
• dermal exposure isn’t common –> ingestion and inhalation are rare but possible
• rapid metabolism through hydrolysis and oxidation
• conjugated metabolites are excreted in urine within 24hrs after exposure
• cats are MORE sensitive than dogs (reduced rate of metabolism becauuse of their shitty liver)
• presence of the alpha-moiety in pyrethroid type 2 decrease metabolism by decreasing hydrolysis
• doesn’t accumulate in tissues

Question 9

what are pyrethroids commonly formulated with for a synergistic effect?

Answer 9

piperonyl butoxide or MGK-264

- both increase toxicity in insects and non-targeted species by delayed metabolism

Question 10

what is the MOA of pyrethrins/pyrethroids?

Answer 10

1. are axonic excitotoxins
2. similar to organochlorine DDT-type MOA
   - neuronal membrane permeability of Na is altered
   - continued NT release
   - hyperexcitability of the nerve –> depolarization –> paralysis
3. type 2 pyrethroids have a greater effect on Na channels
   - similar to organochlorine alicyclic MOA at high concentrations - GABA antagonist
   - inhibit neuronal Ca, Mg ATPase activity –> hyperexcitability

Question 11

what endocrine organ might pyrethrins/pyrethroids stimulate?

Answer 11

adrenal glands

- increased cortisol resulting in hyperglycemia

Question 12

True/False:

insect metabolism of pyrethrins is much faster than that of mammals

Answer 12

FALSE

it’s SLOWER - especially with piperonyl butoxide

Question 13

what are the main clinical signs with acute pyrethrin toxicity?

Answer 13

• generalized muscle tremors, depression, blindness (reversible), ataxia, lethargy
• salivation, vomiting, diarrhea, hyperexcitability, drooling
• may progress to seizures, death

many cats DIE or need to be euthanized because of the severity

Question 14

how do we diagnose pyrethrin toxicity?

Answer 14

• no specific lesions
• generally low tissue levels
• brain and liver in post mortem are best
• tissue levels don’t correlate well

diagnosis is generally made with history and appropriate clinical signs

Question 15

how do we treat pyrethroid toxicity?

Answer 15

• no specific antidote
• decontaminate –> wash with soap/water
• activated charcoal is NOT used (rapid metabolism)
• avoid exacerbating the toxicity (monitor and control temp, treat hyperthermia and prevent hypothermia)
• symptomatic treatment ( methocarbamol for more severe tremors or diazepam/barbs/propofol)

Question 16

what is the prognosis for pyrethrin tox?

Answer 16

good except for cats

Question 17

what is the chemistry of DEET?

Answer 17

• nearly colorless liquid with faint odor
• lipophilic
• relatively stable but sensitive to light

Question 18

what is the MOA of DEET?

Answer 18

• mosquito attraction to a host is thought to involve long-range (visual) and short range (olfactory) stimuli
• lactic acid on the skin may be an essential olfactory stimulant to attract mosquito to land
• effectiveness may be due to its ability to mask sensory perception

Question 19

what is the general toxicity of DEET?

Answer 19

• slightly toxic to some fresh water fish
• dogs are more susceptible, care more sensitive
• young animals more sensitive
• caustic

Question 20

what are the toxicokinetics of DEET?

Answer 20

• dermal absorption (can accumulate and persist in fat)
• guinea pigs - 19-48% of a topical dose absorbed
• can increase dermal absorption of other products
• GI absorption
• metabolized in the liver and excreted in urine

Question 21

what is the MOA of DEET?

Answer 21

• undetermined!
• known to affect the olfactory and nervous system in insects
• when DEET is combined with carbamates the effects are potentiated

Question 22

what are the CS with DEET toxicity?

Answer 22

• rabbits/rats: depression, excitation, ataxia, tremors, seizures, and coma
• dogs/cats: hypersalivation, vomiting, hyperexcitability, tremors, ataxia, seizures, skin and MM irritation

Question 23

how do we diagnose DEET toxicity?

Answer 23

• history, presentation +/- chem analysis
• no specific lesions
• chem analysis can be performed (blood, urine, skin, stomach contents, bile, kidney)
• 20ppm is diagnostic
• must differentiate between other CNS excitatory toxins (strychnine, metaldehyde, organochlorine, OP/carbamate)

Question 24

how do we treat DEET toxicity?

Answer 24

• no specific antidote
• decontaminate
• if dermal: wash with soap and water
• emesis if not contraindicated
• activated charcoal may be given (avoid magnesium cathartics as this may cause CNS depression)

Question 25

what drug can increase dermal absorption of DEET?

Answer 25

pyrethroids