30. Drugs against ectoparasites (except macrocyclic lactones) 2. (phenylpyrazoles, neonicotinoids, isoxazolines, insect growth regulators)

Question 1

Phenylpyrazoles. Drugs

Answer 1

• Fipronile
• Pyriprole

Question 2

Fipronil
(Frontline)

Answer 2

• GABA-antagonist (seizures, excitation SE)
• relatively slow effect
• spot on, spray
• good distribution in the skin
• minimal systemic effect
• shedded hair (allergic dermatitis caused by Dermatophagoides farinae
• minimal toxicity BUT rabbits - signs of excitation, and if rabbit licks the drug -> RIP

Question 3

Pyriprole
(Prac-Tic)

Answer 3

• derivation of fipronil, similar characteristics, GABA-antagonist
• fleas, ticks
• much more effective than fipronil but slow absorption
• NOT IN CATS, RABBITS
• in dogs very safe, even 3-10x overdose is ok

Question 4

Indoxacarb

Answer 4

• Na+ channel blocker -> hyper polarisation
• prodrug -> bioactive metabolite (selective toxicity because becomes active in the flea itself) -> cleavage of methoxy group -> effective flea control (adult, larva, egg)
• flea allergy dermatitis
• safe
• environmentally safe
• combination with pyrethroids -> against ticks

Question 5

Neonicotinoid insecticides (ACh agonists). Drugs

Answer 5

• imadocloprid
• dinotefuran - most potent anti-flea drug
• nitepyram

Question 6

What ectoparacidal combination includes dinotefuran

Answer 6

Dinotefuran + permethrin + pyriproxyfen
(Vectra)

BUT in cats NO permethrin ! - just dinotefuran + pyriproxyfen

Question 7

Imidacloprid
(Advantage, Advocate, Foresto)

Answer 7

• one of the most effective anti-fleas drug
• rapid action
• fleas only
• epithelial debris -> can be accumulated -> FAD treatment
• 5-20x overdose still safe
• collar, spot-on
• +permethrin (Advantix)
• +flumethrin (Foresto)
• +moxidectin (Advocate)

Question 8

Isoxazolines. Drugs. Mechanism of action

Answer 8

• FLURAlaner (Bravecto) - least toxic
• AFOXOlaner
• SAROlaner - most effective
• LOTIlaner
• newest drug group
• no repellent effect

GABA-antagonists, glutamate-gated Cl- channels antagonists
Macrocyclic lactones act on same receptors but bind to different site -> no cross-resistance

• fleas and ticks
• mange mites
• Demodex spp - 1st choice drug
• poultry: Dermanyssus gallinae (fluralaner)

Question 9

Isoxazolines. Combinations

Answer 9

• SAROlaner + selamectin (macrocyclic lactone)
• AFOXOlaner + milbemycin (to cover roundworms)

Question 10

Isoxazolines against Rhipicephalus sanguineus

Answer 10

Rhipicephalus sanguineus - brown dog tick the most resistant tick in vet medicine

Time till 100% of ticks dies:
- fluralaner - 8h
- sarolaner - 12h
- afoxolaner - 48h

For comparison - combination of Imidacloprid and permethrin kills only ~75% of ticks in 48h

Question 11

Isoxazolines. PK

Answer 11

• very good oral absorption
• fluralaner - better with food (2-2,5x better F), sarolaner, afoxolaner - not affected by food
• high protein binding
• slow metabolism
• enterohepatic circulation
• accumulation in adipose tissue
  => long half-life!!! - 10-15 days

Excretion via bile BUT afoxolaner also excreted via kidney -> not to kidney failure patients

Question 12

Isoxazolines. Toxicity

Answer 12

• large TI
• 5x overdose - seizures, tremor, ataxia
• but because it’s GABA-antagonist, SE will disappear within 24h without any treatment
• even ok in MDR-1 mutant dogs
• fluralaner can be given to pregnant and lactating animals (about others there is no evaluation)

Question 13

Insect growth inhibitors. Juvenile hormone analogues

Answer 13

• methoprene (Frontline), pyriproxyfen (Vectra)
• no adulticide effect
• inhibition of larvae development (through eggs, pupae and also digested blood)
• deformity in mature forms if they survive

Question 14

Insect growth regulators. Chitin synthesis inhibitors

Answer 14

• lufenuron
• mainly in agriculture, for crop protection
• not really used in vet practice

Question 15

What drug from Isoxazolines group can’t be given to kidney failure patients?

Answer 15

Afoxolaner because its also excreted via urine