42. parasiticides

which drug class does fenbendazole belong to?

benzimidazoles

what parasites is fenbendazole effective against?

variety of adult helminth parasites

• nematodes

• some cestodes

  • Taenia, NOT Dipylidium

  • Moniezia (in beef cattle)

• some trematodes

• some protozoa

  • Giardia (extra-label)

fenbendazole mechanism of action

• inhibit parasite microtubule function

  • high affinity for parasite tubulin

  • low affinity for mammalian tubulin

• inhibit mitochondrial enzyme function

fenbendazole pharmacokinetics (administration, absorption)

• administration: oral

  • poorly absorbed from GI tract

• small animals: administer minimum of 3 consecutive days

  • dogs: giving with food increases bioavailability

• large animals: slower GI transit times; do not always need 3+ consecutive days

what drug class does pyrantel belong to?

nicotinic anthelmintics

what parasites is pyrantel effective against?

• nematodes

  • but not heartworm (larvae or adults)

• few cestodes

  • Anoplocephala (horses)

pyrantel mechanism of action

• act at parasite nicotinic ACh receptors → cause continued ACh release → continued depolarization

  • mammals have structurally different nicotinic ACh receptors; only weakly activated

• ongoing parasite muscle contraction & rigid paralysis

pyrantel pharmacokinetics (administration, absorption)

• administration: oral

• poorly absorbed from GI tract

  • effective against GI parasites

what drug class does praziquantel belong to?

isoquinolones

what parasites is praziquantel effective against?

• cestodes

• some trematodes (extra-label)

praziquantel mechanism of action

• destroy parasite tegument (mammals do not have) → exposes parasite antigens

  • hosts’s GI and immune system destroy worm

• rigid paralysis → alter flux of cations across tegument

why are nematodes not affected by isoquinolones?

nematodes have a thick outer cuticle; do not have a tegument

praziquantel administration routes

• oral — rapidly absorbed

• injectable — painful

• topical

  • combined with another drug

what drug class does ivermectin belong to?

macrocyclic lactones

what parasites is ivermectin effective against?

• endoparasites: nematodes

  • small animal: heartworm larvae (L3-L4)

    • not heartworm adults

    • cats — also hookworms

  • large animals: many nematodes

• variety of ectoparasites

  • mites

  • lice

  • fly larvae/bots

ivermectin mechanism of action

cause flaccid paralysis in 2 ways:

• hyperpolarize parasite neurons

  • act at glutamate-gated chloride channels → influx of Cl^-

• enhances release of GABA (inhibitory neurotransmitter)

ivermectin pharmacokinetics (administration, absorption)

• administration:

  • oral

  • topical

    • including pour-ons (large animal)

  • injectable

• oral administration

  • non-ruminants: up to 95% absorbed

  • ruminants: some inactivation in rumen → decreased absorption

why is ivermectin safe for mammals?

in mammals:

• no glutamate-gated chloride channels

• GABA receptors limited to CNS

  • BBB protective due to p-glycoprotein (expressed in brain capillary endothelial cells)

ivermectin specific adverse effects

• neurologic signs if it crosses BBB

• sensitivity in collie & herding breeds

  • abnormal p-glycoprotein → ivermectin crosses BBB → neurotoxicity

• however, ivermectin is safe for all dogs at heartworm preventive doses

• toxicity can occur at higher extra-label doses

what drug class does permethrin belong to?

synthetic pyrethroids

what parasites is permethrin effective against?

• ectoparasites

  • fleas

  • ticks

  • lice

  • ear mites

  • adult flies

  • mosquitoes

• some repellent effects too

permethrin mechanism of action

cause rigid paralysis/hyperexcitability

• acts at presynaptic sodium channels → causes influx of Na⁺ ions into nerve cell

• repeated, uncontrolled depolarization

in which species is permethrin toxic? why?

• toxic to cats

  • metabolized via glucuronidation in liver

    • cats inefficient at glucuronide conjugation

  • note: ok to use products specifically labeled for cats

• toxicity causes neurological signs

• (other sensitive species:

  • bees, fish, aquatic invertebrates)

which drug class does fluralaner belong to?

isoxazoline insecticides

which parasites is fluralaner effective against?

• fleas

• ticks

• extra-label: mites, including demodex, sarcoptes

fluralaner mechanism of action

cause rigid paralysis/hyperexcitability

• acts at neuron chloride channels

• cause action potentials to continue without inhibition

fluralaner pharmacokinetics (half-life, administration)

• relatively long half-life

  • allows for longer duration between oral treatments

  • up to 12 weeks

• administration:

  • oral chewable

  • topical

fluralaner adverse effects

• neurologic → do not use in patients with history of seizures

  • ataxia, lethargy, tremors, seizures

• GI

  • inappetence, vomiting, diarrhea