Test 4: 53 insecticides Flashcards
uses of organophosphorous and carbamate insecticides
Topical: plants, animal, soils, household floor
Systemic: absorbed by plants or animals systemically to infect insect upon feeding or via inhalation
sources of exposure to OP’s and carbamate insecticides
- contaminated Livestock feedstuffs with concentrated
- Improper use on crops or animals
- Malicious use
- Secondary or relay toxicosis possible (scavengers eating poisoned animals)
ADME of OP’s and carbamate insecticides
- rapidly absorbed (skin, respiratory and GI tract)
- Rapid distribution and metabolism (P-450 and hydrolysis) with species dependence
- Rapid excretion via urine
- “Sulfone” forms of OP’s are bioactivated to a more toxic “oxon” form
- Variable toxicity among OP’s and carbamates
“Sulfone” forms of OP’s are bioactivated to a more toxic — form
“oxon”
MOA for OPs and carbamates
Competitive inhibition of carboxyl ester hydrolases
* Acetylcholinesterase (found in Red blood cells, brain, retina, NMJs) → Responsible for the breakdown of Ach
* Butyrlcholinesterase found in plasma, liver, pancreas, CNS
how do OPs effect AchE?
will bind to AchE and doesn’t want to let go = irreversible phosphorylation
aging
this leads to ↑AcH activity= continous stimulation of nervous, glandular, and muscular receptors
how does carbamates effect AcHE
reversibly attach to AcHE
will inactivate AcHE for a few minutes (unlike OPs that forever inactive AcHE)
this leads to ↑AcH activity= continous stimulation of nervous, glandular, and muscular receptors
OPs long term effect
cause increased AcH activation on NMJ will cause continuous contractions → muscular paralysis, convulsions and death by asphyxiation once the nerve agent spreads to the diaphragm
treat OP
2-PAM (pralidoxime chloride) reactivates the AChE if given early
2-PAM ineffective after aging occurs
clinical signs of OP
Muscarinic DUMBBELS
* Diarrhea
* Urination
* Miosis
* Bradycardia
* Broncho-constriction
* Emesis
* Lacrimation
* Salivation
Nicotinic: itching, tetany, paralysis → Death generally due to hypoxia (respiratory tract secretions and bronchospasm) or respiratory depression and paralysis.
CNS: dogs and cats: occ seizures, hyperactive and hyperreflexive. LA: hyperactivity, seizures rare
coumaphos
OP
- Systemic insecticide causing a syndrome with slower onset muscarinic and nicotinic signs
- Tetany and seizures may occur prior to death
- Linked to neuro dysfunction in bees
chlorpyrifos
OP
- Cattle exhibit anorexia, diarrhea, rumen stasis, dehydration, and death
- Cats are especially sensitive to chlorpyrifos and develop severe depression, anorexia, tremors, cervical ventroflexion +/- others
- Intermediate syndrome or chronic, low dose exposures are also possible
- Commonly used; in-home use banned in 2001
- Linked to neuro signs, developmental defects and autoimmune disorders in people
how to diagnose OP and carbamates exposure
measure AcHE inhibition
< 50% suspicious, < 25% diagnostic
carbamates may have normal activity
treatment of OP exposure
atropine
vomit
activated charcoal
bathe if topical exposure
if atropine does not work: pralidoxime (2-PAM)
symptomatic and supportive care: respiratory, control seizures, monitor acid base status
may need high dose atropine, careful in horses
OP and carbamates cause PARA: —
NM: —
CNS:—
DUMBELS
tremors → paralysis
coma → seizures
dumbels: Diarrhea, Urination, Miosis, Bradycardia/ Broncho- constriction, Emesis, Lacrimation, Salivation
pyrethrins are —
made from chysanthemum
pyrethrins and pyrethroids are used for
flea control and as insecticidal spray (raid)
MOA of pyrethrins and pyrethroids
↑ Na into the cell by effecting volatge gated sodium channels → excitatory
↑NT release: AcH, GABA, catecholamines
clinical signs of pyrethrins and pyrethroids exposure
Minor:
– Self-limiting
– Hypersalivation, paw flicking, ear twitching, hyperesthesia, reduced activity, single episodes of V/D
Major:
– Protracted vomiting or diarrhea, marked depression or
hyperexcitability, ataxia or muscle tremors
– Rarely seizures and death
– Require immediate veterinary attention!
raid, flea control
why are cats more sensitive to pyrethrins and pyrethroids exposure
↓ glucuronidase activity= slow hydrolysis/breakdown of toxin
treatment for pyrethrins and pyrethroids exposure
emesis
bathe
control seizures, muscle tremors +/- hyperexcitability (valium, barbiturates)
Methocarbamol IV for tremors
20% Intralipid
Prognosis generally good!
Complications
* hyperthermia
* lactic acidosis
* hypoxia
* +/-myoglobinuric nephropathy
— is found in slug and snail baits
metaldehyde
ADME of metaldehyde
- Rapidly absorbed from GIT
- Metabolized to acetaldehyde →Promoted by gastric acidity
- Readily crosses BBB
- Range of lethal doses 60-600 mg/kg → > 2 mg/kg dangerous
MOA of metaldehyde
↓ serotonin and NE
↓GABA (inhibitory)
↑MAO activity
crosses the BBB, ↓ in serotinin and GABA → seizures and acidosis
slug and snail bait
