ORGANOPHOSPHATES Flashcards
ORGANOPHOSPHATES
High lipophilicity
Sensitive to alkaline pH
STORAGE! (moisture → 300-2000x)
Pharmacokinetics
Good absorption (oral 35% > dermal 2-14%)
LD50 po vs LD50 dermal (200-800 vs 2000 mg/kg) Excellent distribution (special barriers, BBB)
Metabolism (partial activation) diazinon (t1/2 hours) → diazoxon (t1/2 days)
Excretion (80% urine metabolites, 20% feces)
long t1/2 + biological accumulation!
cat: increased sensitivity
ORGANOPHOSPHATES
Mechanism of action and side effects
Contact poisons Irreversible inhibition of AChE!
• Muscarinic ACh receptors
SLUDGE (salivation, lacrimation, urination, diarrhea, GI pain, emesis)
• Nicotinic ACh receptors
muscle tremors, spasms
• Central nervous system
seizures, coma, death
Antidote:
Competitive antagonism
SLUDGE <=> Atropine (0.2-0.5 mg/kg iv, sc)
Enzyme reactivation (pralidoxime, obidoxime)
ORGANOPHOSPHATES Application
Broad spectrum in most species (diazinon)
fleas, ticks, lice, mites, myiasis mostly for dipping cats are very sensitive!
Varroosis of honeybees (coumaphos)
vaporizers and fumigant strips
CARBAMATES
Agent: propoxur (Bolfo®, Kiltix®)
Toxicity: much safer (↔atropine)
Pharmacokinetics: less lipophilic, oral vs dermal Fleas, ticks
Collars, aerosol sprays, shampoos
Substances
Diazinon (=dimpylate)
Coumaphos
Phoxim
Fenthion