Anthelmintics: Factors Influencing Use in Companion Animals Flashcards
what are group 1 anthelmintics
Group 1: benzimidazoles (BZ, white drenches)
Fenbendazole (Febantel UK, Panacur, Safe Guard)
what are group 2 anthelmintics
Group 2: levamisoles (LV, yellow drenches)
what are group 3 anthelmintics
Group 3: macrocyclic lactones (ML, clear drenches)
Ivermectin (Heartgard, Ivomec, Eqvalan, Bimectin)
Moxidectin (Coraxis, Cydectin, ProHeart, Advantage, Multi Bravecto Plus, Simparica Trio, Quest - horses)
Milbemycin oxide (in combo products with lufenuron Sentinel)
Selamectin (Revolution, Paradyne)
Eprinomectin (Eprinex, LongRange, Eprizero, Centragard combo with praziquantel)
what are group 4 anthelmintics
Group 4: amino acetonitrile derivatives (AD, orange drenches)
what are group 5 anthelmintics
Group 5: multi-actives
what are examples of praziquantel
Droncit, Drontal, Drontal Plus
what are examples of benzimidazoles
panacur (fenbendazole)
what is the primary action of benzimidazoles
binds helminths tubulin and prevents microtubules formation
tubules absent 6-24 hours
starves parasite
what are other mechanisms benzimidazoles
inhibition of mitochondrial fumarate reductase
reduced glucose transport
uncoupling of oxidative phosphorylation
what is the administration of benzimidazoles
oral administration of suspension
how is benzimidazole absorbed
limited from gut, most leave the dog in feces
how is benzimidazole distributed
plasma levels typically <1% of oral dose
how is efficacy of benzimidazole improved
if gut transit time slowed
how long is benzimidazole present
totally eliminated in 48 hours
what is the metabolism of benzimidazole (3)
variable
- reduction (sulphoxide –> sulphide)
- oxidation (sulphide –> sulphoxide –> sulphone)
- cyclization (ruminants only: netobimin –> albendazole)
sulphides and sulphoxides – ACTIVE
sulphones – INACTIVE
what are examples of macrocyclic lactones
milbemax (milbemycin oxime), stronghold (selamectin) – cats and dogs
animec, bimectin, eqvalan, eraquell (all ivermectin) – horses
what is the spectrum of macrocyclic lactones
stimulate glutamate gated chloride channels in invertebrate nerve and muscles
chloride influx causes hyperpolarization of the post synaptic cells
interferes with neurotransmission
results in flaccid paralysis –> GABA activity may be involved at higher concentrations
what type of compound are macrocyclic lactones
large lipophilic compounds
how long do macrocyclic lactones
generally persistent
long half-life
long period of efficacy
where are macrocyclic lactones distributed
accumulation in fat
how are macrocyclic lactones excreted
bile, urine
but >90% feces
what are the main factors that affect macrocyclic lactone absorption (3)
- route of administration
- formulation
- animal species
what is ivermectin a mix of
two compounds
22,23-dihydroavermectin B1a (80%) and B1b (20%)
what is the half life of ivermectin
approx 3 days for oral
2 days for IV
spot on 10-11 days
how is ivermectin excreted
fecal excretion
why is ivermectin toxic to colies, aussies etc
MDR1 encodes for P glycoprotein pump which prevents ivermectin from entering the brain through the blood brain barrier
if there is an MDR1 mutation then there is no production of the p glycoprotein pump
what is selamectin
modified avermectin
revolution
what is the half life of selamectin
11 days
what is the safety of selamectin
little or no adverse reaction reported
what are the formulations of mibemycin oxime
chewable tablet for cats and dogs
what are the pharmacokinetics of mibemycin oxime
90-95% remains in GIT
what is the safety of mibemycin oxime
transient trembling/ataxia
what is the mechanism of action of tetrahydropyrimidines
stimulate nicotinic acetylcholine receptors (depolarizing neuromuscular blocking agents)
higher affinity for parasite receptor
paralyzes worm
what are examples of tetrahydropyrimidines
embotape, pyratape (pyrantel) – horses
dronal, ednogard (pyrantel combo) – dogs and cats
how are tetrahydropyrimidines absorbed
not well absorbed from GIT
how are tetrahydropyrimidines excreted
50% excreted unchanged remainder in feces
what are tetrahydropyrimidines effective against
very effective against GIT luminal parasites
how is the tissue penetration of tetrahydropyrimidines
poor
what is the mechanism of action of praziquantel
tetanic contraction of parasite musculature
rapid vacuolization of the syncytial tegument
what are the safety issues with praziquantel
high therapeutic index
what is the spectrum of activity of praziquantel
cestodes, trematodes
efficacy vs. larval cestodes very variable
how is praziquantel absorbed
rapidly absorbed, widely distributed
how is praziquantel metabolized
70% first pass metabolism
80% eliminated within 24 hours
what is the mechanism of action of cyclooctadepsipeptides
inhibition of acetylcholine-elicited muscle contraction
pre-synaptic action (iatrophilin like receptor)
ultimately flaccid paralysis/death
what is the spectrum of activity of cyclooctadepsipeptides
adult nematodes
what is the pharmacokinetics cyclooctadepsipeptides
extensively distributed
high Vd
minor metabolism
excreted unchanged in the bile
