MACROCYCLIC LACTONES Avermectins and milbemycins

Question 1

MACROCYCLIC LACTONES Avermectins and milbemycins

Answer 1

Mechanism of action: GluCl and GABA agonist Spectrum: fleas (selamectin!) mange mites Demodex spp. (differences!) → moxidectin (1x weekly) and milbemycin (1x daily) myiasis ticks (slow killing, not repellents)
Selamectin <=> ivermectin receptors in the pharynx of fleas relatively slow (8h 75%), but persistent

Question 2

Fipronil (Frontline A.U.V)

Answer 2

GABA-antagonist
Relatively slow effect (8h 40-60%)
Spot on, spray
Good distribution in the skin (sweat and sebaceous glands) → good residual activity (bathing)
Minimal systemic effect
Shedded hair > 2 weeks (Dermatophagoides farinae)

Decreased susceptibility?
Minimal toxicity (10x binding to GABA-receptors), but in rabbits! signs of excitation 0,1% vs 50% dermal vs per os

Question 3

Pyriprole (Prac-Tic A.U.V)

Answer 3

Derivate of fipronil
Similar characteristics, GABA-antagonist
Fleas, ticks

Resistance has not yet been observed 
Much more effective, but slow absorption (50%), 
Ø bathing within 48h
Cats, rabbits Ø 
Dogs 3-10x overdose

Question 4

Indoxacarb (Activyl A.U.V)

Answer 4

Na+ channel blocker→ hyperpolarization
used in agriculture→ resistance?

Prodrug → bioactive metabolite (selective toxicity)→ cleavage of methoxy group→ effective flea control (adult, larva, egg!)
Feeding & oviposition stops within 0-4 hours
Death within 4-48 hours
Flea allergy dermatitis (FAD)
Safe usage Environmentally safe