Antiparasitics Large Animals Pharmacology

Front 1

What do you have to be really careful about when using anti-parasitic meds off label in large animals?

Back 1

Have to worry about drug residues in food

Front 2

What 2 drugs are the majority of dewormers in cattle?

Back 2

Ivermectin & fenbendazol
-Except for specific indications such as flukes
-Add pyrantel for horses

Front 3

*The ______ and _________ drugs account for over 80% of the available dewormer products.

Back 3

Benzimidazoles and avermectins

Front 4

What is the focus group of ruminant worms?

Back 4

GI nematodes

Front 5

What are the 3 major avermectins used as large animal anti-parasitics?

Back 5

1) Ivermectin
2) Doramectin
3) Eprinomectin

Front 6

Which of the 3 major avermectins are not naturally occurring avermectins?

Back 6

Eprinomectin

Front 7

*What is Ivermectin soluble in?

Back 7

Insoluble in water
Soluble in methanol and ethanol
-So comes in paste
-Lipophilic=wide distribution!

Front 8

*Does ivermectin cross the blood brain barrier in mammals at therapeutic doses?

Back 8

NO!!

Front 9

*What is the big difference b/w Doramectin and Ivermectin?

Back 9

Doramectins elimination half-life is about double that of ivermectin in cattle-so don't have to use as frequently

Front 10

What is the benefit of Eprinomectin compared to Doramectin and Ivermectin?

Back 10

No milk withdrawl time so can use in lactating animals

Front 11

*What is the mechanism of action of avermectins?

Back 11

-Bind a high-affinity receptor on the invertebrate glutamate-gated chloride channel
-Causes influx of Cl- into cells, leading to hyperpolarization and subsequent paralysis of worms so can't more or eat

Front 12

*Describe the volume of distribution of Avermectins.

Back 12

Lipid soluble so have a very high volume of distribution

Front 13

*How long is the half-life of Ivermectin in cattle? How long does activity persist?

Back 13

Half-life: 2-3 days
Activity can persist up to 21 days

Front 14

*How do avermectins exist in the blood?

Back 14

~93% are protein bound in the blood

Front 15

*The oral bioavailability of avermectins in ruminants is about ____-____%.

Back 15

25-33%
w/ large amounts of unchanged drug excreted in feces

Front 16

*Compare the oral bioavailability of avermectins in horses to ruminants.

Back 16

Horses probably absorb much more (~95%) compared to 25-33% in ruminants

Front 17

*What is the spectrum of activity of avermectins?

Back 17

*Most internal nematodes
*Not effective against flukes or tapeworms.

Front 18

*What is different about the spectrum of activity of Doramectin compared to the other avermectins?

Back 18

Also effective against the screwworm, Cochliomyia, biting lice and chorioptes

Front 19

*True or false. Resistance isn't a very big concern with avermectins.

Back 19

False! Resistance is an increasingly important phenomenon, seen in strongyles in goats and resistance in haemonchus

Front 20

*What does resistance in avermectins appear to be related to?

Back 20

Mutations in a number of ligand-gated chloride channels

Front 21

*Label doses of anti-parasitics are for cattle, sheep, horses and pigs, so how should the dose be modified for most dewormers in goats & camelids?

Back 21

May require 1.5-2x the label dose

Front 22

*Avermectins should be used with care in animals suspected of having what condition?

Back 22

Damage to the blood brain barrier

Front 23

*How do avermectins decrease degradation activity in the environment?

Back 23

Retain activity in feces and other body tissues and fluids so kills things such as dung beetles that have degrading activity in environment
-Once in contact with soil it becomes inactive

Front 24

*Moxidectin has a similar MOA to the avermectins, but how is it different?

Back 24

Longer half-life

Front 25

What agent works better than most agents against encysted larvae in horse?

Back 25

Moxidectin

Front 26

*Why can moxidectin be good for use in pregnant cattle?

Back 26

No milk discard

Front 27

*What are 5 benzimidazoles?

Back 27

1) Fenbendazole
-By far most common in ruminants
2) Oxfendazole
3) Albendazole
4) Oxibendazole
5) Triclabendazole

Front 28

*What 3 benzimidazoles are insoluble in water?

Back 28

1) Fenbendazole
2) Oxfendazole
3) Albendazole

Front 29

What animals are oxibendazole used in?

Back 29

Only horses in the US

Front 30

True or false. Albendazole is not available in the US.

Back 30

False, triclabendazole is the only benzimidazole not available in US

Front 31

*What is the major MOA of benzimidazoles?

Back 31

Binding to the colchicine-sensitive site of beta tubulin, thus inhibiting its polymerization---> degenerative alterations in the tegument and intestinal cells of the worm --> impaired uptake of glucose---> degenerative changes and subsequent release of lysosomes--> decreased production of ATP--> death

Front 32

*What allows for benzimidazole's selectivity activity against parasite and not host cells?

Back 32

Comes from poor absorption and the higher affinity in binding parasitic VS mammalian microtubules

Front 33

*What prolongs the contact time of benzimidazoles with the target invertebrates?

Back 33

Slow GI transit

Front 34

*True or false. The killing efficacy of benzimidazoles is related to the systemic concentrations of the drug.

Back 34

False, not concentration dependent-dependent on GI transit time

Front 35

*What is the secondary mechanism of action of benzimidazoles?

Back 35

Involves inhibition of fumarate reductase (which is helminth-specific) --> uncouples oxidative phosphorylation

Front 36

*What are the repercussions associated with the water insolubility of benzamidazoles?

Back 36

Minor changes in the molecule may have relatively large impacts on absorption

Front 37

How are benzimidazoles administered? Why?

Back 37

Orally, most have poor oral absorption but are so insoluble that other routes are impractical

Front 38

How do the majority of benzimidazoles exist in the blood? Volume of distribution? elimination rate?

Back 38

Less than 50% protein bound, so have a relatively high volume of distribution and a relatively fast elimination rate

Front 39

*What is the spectrum of activity of benzimidazoles?

Back 39

Most internal worms, affect larvae and adults

Front 40

*What 2 benzimidazoles are effective against Fasciola?

Back 40

Albendazole and Triclabendazole

Front 41

What is the only ruminant dewormer labeled for use against tapeworms?

Back 41

Benzimidazoles

Front 42

*What type of resistance issues are developing in benzimidazoles?

Back 42

Point mutations in beta tubulin genes is leading to lower affinity forms that are similar to mammalian beta tubulin

Front 43

*What is the most important adverse effect of benzimidazoles as a group?

Back 43

Bone marrow suppresion!

Front 44

What benzimidazole should not be used in early pregnancy? Why?

Back 44

Albendazole is teratogenic and embryotoxic

Front 45

What are the 2 major dewormers of large animals?

Back 45

Avermectins
Benzimidazoles

Front 46

What are the 6 minor dewormers used in large animal medicine?

Back 46

1) Levamisole
2) Clorsulon
3) Praziquantel
4) Piperazine
5) Pyrantel/morantel
6) Dichlorvos

Front 47

*What is the mechanism of action of levamisole?

Back 47

Nictonic agonist, neuromuscular stimulation leads to tetanic paralysis
-Also interferes w/ famarate reduction
-Similar MOA to pyrantel

Front 48

*What is the spectrum of activity of levamisole?

Back 48

Gi Nematodes and lungworms
*Encysted larvae are refractory

Front 49

*What are 5 adverse effects of levamisole?

Back 49

1) Mild local irritation at injection site
Sometimes label doses in sheep:
2) Transient tremors
3) Salivation
4) Lip-licking
5) Evidence of heightened alertness

Front 50

*What drug is used specifically against Fasciola and other liver flukes?

Back 50

Clorsulon

Front 51

*What are the 2 forms of clorsulon that are available?

Back 51

Just clorsulon=oral
Injectable combined with Ivermectin

Front 52

*At label doses of clorsulon PO in cattle and sheep, is it larvicidal or adulticidal? Label doses of injection ivermectin combo?

Back 52

Oral Clorsulon: Both larvicidal and adulticidal
Injectable combo: only adulticidal, not larvicidal

Front 53

*What is the mechanism of action of praziquantel?

Back 53

Affects calcium ion permeability, leading to increased neuromuscular activity and flaccid paralysis.
-At higher doses also causes tegmental damage, which may allow immune system to attack parasite

Front 54

*What is the spectrum of activity of praziquantel?

Back 54

Cestodes and trematodes

Front 55

What is the only licensed large animal product of praziquantel in the US?

Back 55

Combination products for horses

Front 56

*What is the mechanism of action of piperazine?

Back 56

GABA-receptor agonist leading to influx of chloride, hyperpolarization and flaccid paralysis.

Front 57

*How is piperazine administered? in what animals?

Back 57

Per os in horses or pigs
-Rarely used in ruminants!

Front 58

What is the oral absorption of piperazine like? Elimination?

Back 58

-Rapidly absorbed PO
-Rapidly excreted in urine
*Short acting

Front 59

What is the mechanism of action of pyrantel/morantel?

Back 59

Nicotinic agonists

Front 60

What is different about pyrantel/Morantel metabolism in ruminants?

Back 60

rapidly metabolized in ruminants

Front 61

*How often is pyrantel/morantel administered?

Back 61

Daily in feed supplement

Front 62

What is dichlorvos used for?

Back 62

Internal dewormer in pigs ONLY

Front 63

What are 6 antiprotozoal medications?

Back 63

1) Amprolium
2) Sulfa antibiotics
3) Ionophors
4) Decoquinate
5) Ponazuril and other Benzacetonitriles
6) Fenbendazole (can be used against giardia)

Front 64

*What is the mechanism of action of amprolium? What's it used against?

Back 64

Inactive thiamine analog
-Used against coccidia

Front 65

*What stage of protozoa is amprolium most effective against?

Back 65

First generation schizonts
-So is most beneficil as a preventative or in animals recently/ currently ingesting sporulated oocysts

Front 66

*What is the primary adverse effect of amprolium?

Back 66

Polioencephalomalacia (central blindness, ataxia, seizures)

Front 67

What protozoa can sulfa antibiotics be used against?

Back 67

Coccidia in swine & ruminants
-Interferes w/ folate metabolism

Front 68

*What is the mechanism of action of ionophores as an antiprotozoal agent?

Back 68

Form complexes w/ sodium or potassium and increase the parasite's membrane permeability, affecting mitochondrial function
"Iono-pores"

Front 69

*What stage of protozoa are ionophores most effective against?

Back 69

Trophozoites and s most useful as preventative

Front 70

*Ionophores at label doses are considered safe in pigs and ruminants, but what adverse effects occur in horses at label dose and ruminants at higher doses?

Back 70

Cardiotoxic

Front 71

If you look in the literature for toxicity most common in horses that get bovine or pig feed, what drug is responsible?

Back 71

Ionophores
-Cardiotoxicity in horses at label dose

Front 72

*What is the mechanism of action of decoquinate? What is it effective against?

Back 72

Disrupts electron transport in the parasite's mitochondrial cytochrome system
-Feed additive that prevents coccidial infections

Front 73

*What stage of the protozoal life cycle is decoquinate most effective against?

Back 73

Sporozoites -used as preventative

Front 74

*Ponazuril is marketed in in the US exclusively as a treatment for what?

Back 74

Equine protozoal myelitis, caused by sarcocystic neurona

Front 75

*Why does it take a while for ponazuril and other benzacetonitriles to take effect?

Back 75

slow gut absorption

Front 76

*What part of protozoal life development does ponazuril and other benzacetonitriles target?

Back 76

Damage all intracellular & extracellular stages

Front 77

*What is the mechanism of action of ponazuril and other benzacetonitriles?

Back 77

Affect division of nucleus, activity of the mitochondria and wall-forming body formation, producing severe vacuolization of the ER

Front 78

What protozoa can fenbendazole be used against?

Back 78

Giardia

Front 79

**When is metronidazole legal in food animals?

Back 79

ONLY when following the label

Front 80

What are 4 drugs used to kill ectoparasites in large animals?

Back 80

1) Avermectins
2) Organophosphates
3) Amitraz
4) Pyrethrins

Front 81

*What 3 ectoparasites are avermectins good at killing?

Back 81

1) Ticks
2) Lice (sucking> chewing)
3) Burrowing mites

Front 82

*What represents the first generation of organophosphates?

Back 82

Dichlorvos

Front 83

*What is the elimination rate of first generation organophosphates like?

Back 83

Quickly broken down

Front 84

*Organophosphates have good killing potential, but little ______ effect.

Back 84

Residual

Front 85

*What is a big benefit of the second generation of organophosphates? What are the side effects of organophosphate toxicosis?

Back 85

Can be used in lactating cows
-Toxicosis: Acute-SLUD signs; chronic-degeneration of long axons of nerves

Front 86

*What is the mechanism of action of amitraz?

Back 86

Octopaminergic agonist, affecting insect adenylate cyclase
-Discourage in horses because of colonic impactions

Front 87

*Compare pyrethrins to pyrethroids.

Back 87

Pyrethrins: natural products of flowerhead of chrysanthemums
Pyrethroids: synthetic variants, that usually have greater potency and durability

Front 88

*What is the mechanism of action of pyrethrins?

Back 88

Disrupt sodium and potassium transport on insect's nervous membranes, affecting neurotransmission and have some repellent efficacy too

Front 89

*What is the therapeutic index of pyrethrins in mammals like?

Back 89

Generally very safe in mammals, but are toxic to fish and occasionally neonates

Front 90

*How long can the action of pyrethroids on ear tags last? Topicals?

Back 90

Ear tags:Up to 5 months!
Topicals: may last 2-3 weeks

Front 91

*There is some evidence of _____ developing resistance to pyrethroids.

Back 91

Flies
-So a rotation of strategies is advised