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
clinical signs of Metaldehyde exposure
- Anxiety, tachycardia, restlessness
- Nystagmus > cats
- Mydriasis, tremors, ataxia (esp cattle and sheep), colic in horses
- Polypnea, tachycardia, opisthotonus, convulsions, hyperthermia, acidosis
- Delayed signs: depression and coma
- Liver failure 2-3 days after exposure
- Death possible from respiratory failure
treatment of metaldehyde exposure
vomit
control seizures/tremors
ventilate if needed
control hyperthermia
IV fluids
Sodium bicarbonate (for acidosis): caution
Prognosis: good if treated early
amitraz is found in
flea collars
should never be used on cats or horses
— is a ⍺2 agonist and weak MAO inhibitor
amitraz (dog flea collars)
can cause light sedation or death in high doses
dog is 15 kg
9.0% amitraz collar
collar weighs 27.5 g
toxic dose is 40 mg/kg
change collar?
27.5g → 27500 mg
27500mg (0.09)= 2475 mg
2475mg/15 kg= 165 mg/kg
need to decrease collar
clinical signs of amitraz exposure
Relate to CNS and cardiovascular effects of toxicant.
- ataxia, depression, disorientation, polyuria, vocalization, seizures
- bradycardia
- some GI signs: emesis, diarrhea, anorexia
⍺2 agonist
treatment for amitraz exposure
GI: emesis
bathe
intralipid
α-adrenergic antagonists such as yohimbine or atipamizole (antiseden) (less cardiorespiratory effects)
what are some macrolide endectocides
Ivermectin
Selemectin
Abamectin
Doramectin
Milbemycin
how do macrolides work
↑ GABA (inhibitory)
what animals are more sensitive to macrolides
collies
lack p-glycoprotein at BBB so macrolides (ivermectin,selemectin) can cross into BBB
white feet don’t treat
citrus oil extracts MOA
not really known
central and peripheral vasodilation?
clinical signs of citrus oil exposure
CNS depression and ↓temp
salivation, skin irritation, tremors
Often resolve in 6 to 12 hours with supportive care and bathing
— effect the Na channels and cause hyperexcitability, tremors and seizures
pyrethrins and pyethroids
ivermectin work on — receptors and overdose causes —
GABA
Anxiety Restlessness Mydriasis Tremors Ataxia Polypnea Tachycardia Opisthotonus Convulsions Hyperthermia
metaldehyde work on — and cause —
↓GABA and serotonin
Anxiety Restlessness Mydriasis Tremors Ataxia Polypnea Tachycardia Opisthotonus Convulsions Hyperthermia
acidosis, nystagmus, liver failure 2-3 days after exposure
OPs and carbamates work on — and cause
block AcHE
DUMBELS
Muscle Fasiculations Weakness Mydriasis Tachycardia Bradycardia Hypertension Bronchodilation Excitability Lethargy Agitation Coma Seizure
amitraz works on — and causes
⍺2 agonist
Ataxia Depression Disorientation
Vocalization Seizures Bradycardia Emesis Diarrhea Anorexia
