ISOXAZOLINES

Question 1

ISOXAZOLINES substances

Answer 1

Fluralaner (Bravecto®) 
Afoxolaner (Nexgard®) 
Sarolaner (Simparica®) 
Lotilaner (Credelio®) 
– GABA-antagonist, glutamate-gated Clchannel antagonist

Question 2

– oral antiparasitic agents

Answer 2

Drawbacks of spot ons/collars
– contact dermatitis
– bathing/washing off/getting wet
– usually does not cover the whole body

Question 3

Efficacy

Answer 3

– Fleas + ticks 
– Fleas within 8 hours 
– Ticks within 12 hours (Lyme, Babesia)
– Mange mites 
– Demodex spp. 
– Poultry: Dermanyssus gallinae (fluralaner)

Question 4

Combos

Answer 4

Sarolaner + selamectin

Afoxolaner + milbemycin

Question 5

Pharmacokinetics

Answer 5

– Oral absorption: tmax 1 day 
– Feeding (2,1-2,5x) fluralaner ↔ sarolaner, afoxolaner 
– High plasma protein binding 
– Slow metabolism 
– Enterohepatic circulation 
– Accumulation in adipose tissues
→ long half-life (10-15 days)

– Afoxolaner: also excreted by kidneys
– Fluralaner (0,01%), sarolaner: almost entirely via bile
– Enterohepatic circulation: fluralaner
Fluranaler vs sarolaner/afoxolaner duration of action: 25-56 mg/kg vs 2-4 mg/kg

Question 6

Toxicity

Answer 6

– Large differences between LD50 and therapeutic doses
– Sarolaner: 1x, 3x, 5x doses, 8 weeks old puppies
•3x overdose: tremors, ataxia (12 mg/kg)
•5x overdose: seizures, tremors, ataxia (20 mg/kg)

GABA-antagonism! (resolves within 24 hours)

– In MDR-1 mutant Collies
– 3-5x overdose
None of them were found to be toxic
Agents have not been evaluated in pregnant or lactating animals (↔fluralaner)

Question 7

INSECT GROWTH REGULATORS JUVENILE HORMONE ANALOGUES

Answer 7

methoprene (Frontline Combo®)
pyriproxyfen (Duowin®, Vectra 3D®) → even 48 days

Ø adulticide effect!
Inhibition of larval development (through eggs, pupas, and also with digested blood)
Deformity of mature forms, if they survive
Light, residual activity: pyriproxyfen > methoprene

Question 8

CHITIN SYNTHESIS INHIBITORS

Answer 8

(mainly in agriculture) lufenuron (Program®) novaluron