How are pyrethrin/pyrethroids used?
- home and farm insecticide
- farm animals
- companion animals (fleas/ticks)
most cannot be used on cats
what is the relationship between pyrethrins and pyrethroids?
pyrethroids are synthetic analogs of pyrethrins
- pyrethroids now make up the majority of commercial household insecticides (like BOP)
are pyrethrins water or lipid soluble?
lipid
so synthetic pyrethroids or natural pyrethrins have higher risk for acute toxicity?
natural pyrethrins
how does an animal get a chronic toxicity to pyrethrins?
respiration mainly, less by dermal
What are the different toxicity levels with pyrethrins?
- high toxicity in bees
- high acute toxicity in fish and aquatic invertebrates
- high acute toxicity in cats
which generation of pyrethroids are more toxic?
second generation (type 2) - do not contain alpha-cyano moiety which increases insecticidal potency and decreases metabolism
what are the toxicokinetics of pyrethroids?
- 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
what are pyrethroids commonly formulated with for a synergistic effect?
piperonyl butoxide or MGK-264
- both increase toxicity in insects and non-targeted species by delayed metabolism
what is the MOA of pyrethrins/pyrethroids?
- are axonic excitotoxins
- similar to organochlorine DDT-type MOA
- neuronal membrane permeability of Na is altered
- continued NT release
- hyperexcitability of the nerve –> depolarization –> paralysis - 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
what endocrine organ might pyrethrins/pyrethroids stimulate?
adrenal glands
- increased cortisol resulting in hyperglycemia
True/False:
insect metabolism of pyrethrins is much faster than that of mammals
FALSE
it’s SLOWER - especially with piperonyl butoxide
what are the main clinical signs with acute pyrethrin toxicity?
- 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
how do we diagnose pyrethrin toxicity?
- 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
how do we treat pyrethroid toxicity?
- 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)
what is the prognosis for pyrethrin tox?
good except for cats
what is the chemistry of DEET?
- nearly colorless liquid with faint odor
- lipophilic
- relatively stable but sensitive to light
what is the MOA of DEET?
- 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
what is the general toxicity of DEET?
- slightly toxic to some fresh water fish
- dogs are more susceptible, care more sensitive
- young animals more sensitive
- caustic
what are the toxicokinetics of DEET?
- 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
what is the MOA of DEET?
- undetermined!
- known to affect the olfactory and nervous system in insects
- when DEET is combined with carbamates the effects are potentiated
what are the CS with DEET toxicity?
- rabbits/rats: depression, excitation, ataxia, tremors, seizures, and coma
- dogs/cats: hypersalivation, vomiting, hyperexcitability, tremors, ataxia, seizures, skin and MM irritation
how do we diagnose DEET toxicity?
- 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)
how do we treat DEET toxicity?
- 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)
