Anthelmintics: Factors Influencing Use in Companion Animals

Question 1

what are group 1 anthelmintics

Answer 1

Group 1: benzimidazoles (BZ, white drenches)

Fenbendazole (Febantel UK, Panacur, Safe Guard)

Question 2

what are group 2 anthelmintics

Answer 2

Group 2: levamisoles (LV, yellow drenches)

Question 3

what are group 3 anthelmintics

Answer 3

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)

Question 4

what are group 4 anthelmintics

Answer 4

Group 4: amino acetonitrile derivatives (AD, orange drenches)

Question 5

what are group 5 anthelmintics

Answer 5

Group 5: multi-actives

Question 6

what are examples of praziquantel

Answer 6

Droncit, Drontal, Drontal Plus

Question 7

what are examples of benzimidazoles

Answer 7

panacur (fenbendazole)

Question 8

what is the primary action of benzimidazoles

Answer 8

binds helminths tubulin and prevents microtubules formation

tubules absent 6-24 hours

starves parasite

Question 9

what are other mechanisms benzimidazoles

Answer 9

inhibition of mitochondrial fumarate reductase

reduced glucose transport

uncoupling of oxidative phosphorylation

Question 10

what is the administration of benzimidazoles

Answer 10

oral administration of suspension

Question 11

how is benzimidazole absorbed

Answer 11

limited from gut, most leave the dog in feces

Question 12

how is benzimidazole distributed

Answer 12

plasma levels typically <1% of oral dose

Question 13

how is efficacy of benzimidazole improved

Answer 13

if gut transit time slowed

Question 14

how long is benzimidazole present

Answer 14

totally eliminated in 48 hours

Question 15

what is the metabolism of benzimidazole (3)

Answer 15

variable

1. reduction (sulphoxide –> sulphide)
2. oxidation (sulphide –> sulphoxide –> sulphone)
3. cyclization (ruminants only: netobimin –> albendazole)

sulphides and sulphoxides – ACTIVE

sulphones – INACTIVE

Question 16

what are examples of macrocyclic lactones

Answer 16

milbemax (milbemycin oxime), stronghold (selamectin) – cats and dogs

animec, bimectin, eqvalan, eraquell (all ivermectin) – horses

Question 17

what is the spectrum of macrocyclic lactones

Answer 17

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

Question 18

what type of compound are macrocyclic lactones

Answer 18

large lipophilic compounds

Question 19

how long do macrocyclic lactones

Answer 19

generally persistent

long half-life

long period of efficacy

Question 20

where are macrocyclic lactones distributed

Answer 20

accumulation in fat

Question 21

how are macrocyclic lactones excreted

Answer 21

bile, urine

but >90% feces

Question 22

what are the main factors that affect macrocyclic lactone absorption (3)

Answer 22

1. route of administration
2. formulation
3. animal species

Question 23

what is ivermectin a mix of

Answer 23

two compounds

22,23-dihydroavermectin B1a (80%) and B1b (20%)

Question 24

what is the half life of ivermectin

Answer 24

approx 3 days for oral

2 days for IV

spot on 10-11 days

Question 25

how is ivermectin excreted

Answer 25

fecal excretion

Question 26

why is ivermectin toxic to colies, aussies etc

Answer 26

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

Question 27

what is selamectin

Answer 27

modified avermectin revolution

Question 28

what is the half life of selamectin

Answer 28

11 days

Question 29

what is the safety of selamectin

Answer 29

little or no adverse reaction reported

Question 30

what are the formulations of mibemycin oxime

Answer 30

chewable tablet for cats and dogs

Question 31

what are the pharmacokinetics of mibemycin oxime

Answer 31

90-95% remains in GIT

Question 32

what is the safety of mibemycin oxime

Answer 32

transient trembling/ataxia

Question 33

what is the mechanism of action of tetrahydropyrimidines

Answer 33

stimulate nicotinic acetylcholine receptors (depolarizing neuromuscular blocking agents) higher affinity for parasite receptor paralyzes worm

Question 34

what are examples of tetrahydropyrimidines

Answer 34

embotape, pyratape (pyrantel) -- horses dronal, ednogard (pyrantel combo) -- dogs and cats

Question 35

how are tetrahydropyrimidines absorbed

Answer 35

not well absorbed from GIT

Question 36

how are tetrahydropyrimidines excreted

Answer 36

50% excreted unchanged remainder in feces

Question 37

what are tetrahydropyrimidines effective against

Answer 37

very effective against GIT luminal parasites

Question 38

how is the tissue penetration of tetrahydropyrimidines

Answer 38

poor

Question 39

what is the mechanism of action of praziquantel

Answer 39

tetanic contraction of parasite musculature rapid vacuolization of the syncytial tegument

Question 40

what are the safety issues with praziquantel

Answer 40

high therapeutic index

Question 41

what is the spectrum of activity of praziquantel

Answer 41

cestodes, trematodes efficacy vs. larval cestodes very variable

Question 42

how is praziquantel absorbed

Answer 42

rapidly absorbed, widely distributed

Question 43

how is praziquantel metabolized

Answer 43

70% first pass metabolism 80% eliminated within 24 hours

Question 44

what is the mechanism of action of cyclooctadepsipeptides

Answer 44

inhibition of acetylcholine-elicited muscle contraction pre-synaptic action (iatrophilin like receptor) ultimately flaccid paralysis/death

Question 45

what is the spectrum of activity of cyclooctadepsipeptides

Answer 45

adult nematodes

Question 46

what is the pharmacokinetics cyclooctadepsipeptides

Answer 46

extensively distributed high Vd minor metabolism excreted unchanged in the bile