Parasiticide MOA

Why do parasiticides have numerous unique MOAs?

They targets of these drugs are exceptionally genetically diverse

Albendazole class

Benzimidazole

Fenbendazole class

Benzimidazole

Oxfendazole class

Benzimidazole

Febantel

Benzimidazole Pro Drug

What is the MOA of benzimidazoles?

Inhibition of microtubule polymerization in nematodes but NOT animal cells

What should you not use albendazole in?

Animals in first 1/3rd of pregnancy

How are all benzimidazoles administered?

Orally

PK of benzimidazoles in dogs cats humans

Oral oral and may require a higher dose or frequency due to limited rates of absorption

PK of benzimidazoles in horses?

Reduced bioavailability and shorter residence times

PK of benzimidazoles in ruminants

Systemic distribution

Limited water solubility

Reduced GI transit increases absorption

What benzimidazole is not completely absorbed in ruminants?

Fenbendazole

What drug has a rumen reservoir effect leading to an extended period of distribution?

Benzimidiazoles

Fenbendazole adverse effects

Rare vomiting and diarrhea

Pancytopenia

Albendazole adverse effects

Teratogenic and embryogenic in pregnant animals

Idiosyncratic myelosuppression in dogs and cats

When can you not give albendazole to female cattle?

First 45 days of pregnancy or 45 days after removal of bulls

When do you not give albendazole to ewes or does?

First 30 days of pregnancy or 30 days after removal of rams or bucks

Benzimidazoles adverse effects

Toxic to liver and bone marrow in dogs

What are benzimidazoles not recommended to be used in?

Cats

What is albendazole used for in cattle and sheep?

Liver flukes, tapeworms, GI worms, lung worms

What is fenbendazole used for in cattle?

GI worms and lungworms at a low dose

Tapeworms and L4 of Ostertagia at high doses

What is fenbendazole used for in horses?

Strongyles, pinworms ascarids

What is fenbendazole used for in goats?

GI worms and lung worms

What is fenbendazole used for in dogs?

Giardia, roundworms, hookworms, whipworms

What is oxfendazole used for in cattle?

Lungworms, GI nematodes, tapeworms

What is fenbendazole not approved for use in?

Cats

What nicotinic agonist has a low margin of safety?

Levamisole

Macrocyclic lactone adverse effects?

Safe except for MDR1 double recessive dogs (always safe at HW dose(

Acute toxic signs include CNS depression, ataxia, and death

Melarsomine class

Arsenical

MOA of melarsomina

Not well understood

Arsenic interacts with sulfhydryl groups to prevent enzymes and disrupt aerobic metabolism

Melarsomine indication

Dirofilaria immitis

Melarsomine PK

Rapidly absorbed IM

Cmax after 8 minutes

Arsenic plasma levels are high for a long time

Melarsomine safety/toxicity

Overdose is dose is done in mg/lb instead of mg/kg (2.2x the dose)

Excessive salivation, panting, restlessness, and fever; vomiting at diarrhea

What is dimercaprol?

Antidote for arsenic toxicity by sulfahydryl group forming heavy metal complexes

What dose of melarsomine is fatal?

3x the dose

Praziquantel class

Isoquinoline-pyrazine

Praziquantel MOA

Ca2+ channel agonist to create a rapid and sustained paralytic muscle contraction

What metabolic changes does praziquantel do?

Decrease in glucose uptake, glycogen storage, ATP content, lactate release

Administration of praziquantel

Oral or injectable

Describe praziquantel in cats

Topical in combination with emodepside

When does overdose of praziqunatel occur?

Very hard, can go 5x the dose without adverse reactions

What is the indication for metronidazole (FLAGYL)?

Trichomonas, Giardia, Entamoeba, Balantidium

Intestinal microbiome is ALSO affected

Usage of metronidazole in dogs and cats?

Giardia

What dogs should not get metronidazole?

Pregnant dogs

Benzoylmetronidazole is not FDA approved in what but is used anyway?

Cats with giardia

What is a notorious effect of metronidazole?

Unpalatable and can cause loss of appetitie

Rodinazole class

Nitroimidazole

Ronidazole uses?

Cats: Tritrichomonas

Dogs: kennel situations

T/F metronidazole can be used alone on giardia?

False

Where is ronidazole available?

Compounding pharmacies

What are benzimidazoles indicated for against protozoa?

Giardia

What should you do after giving fenbendazole to a dog with giardia?

Bathe animal after

What cats can get fenbendazole for giardia?

Large zoo cats, not approved for domestic cats

Monensin adverse effects

Will cause deaths in horses dur to being a cardio-toxin

C/S of monensin toxicity in horses?

Tachycardia/cardiac arrythmia, groaning, incoordination, recumbency and paddling movement with the limbs before death

Monensin class

Ionophore

T/F other ionophores other than monensin is toxic to horses?

True (salinomycin, narasin, and others probably)

What is sulfonamides and diaminopyrimidines approved for?

Treating bacterial enteritis associated with coccidiosis in dogs. Not for coccidia itself

Why can you never give dinotefuran dog formulation to cats?

It has permethrin and will kill the cat

Isoxazoline MOA

GABA receptor antagonist with non-competitive of gamma-aminobutyric acid

Binds to Cl channels and blocks influx of Cl ions

What is the difference in the MOA of isoxazolines and Phenylpyrazoles?

Isoxazolines bind to different and specific receptor sites

What are the isoxazolines?

Afoxolaner, esafoxolaner, fluralaner, sarolaner, lotilaner

What class is pyrantel?

Nicotinic agonist

What class is morantel?

Nicotinic agonist

What is the PK of pyrantel tartate?

Well absorbed in oral administration in most species except for ruminants

What is the PK of pyrantel pamoate?

Water insoluble and poorly absorbed

What is the benefit of having pyrantel pamoate be poorly abosrbed?

It increases safety of the drug in young or weak animals

What is the PK of morantel?

Poorly absorbed in ruminants

What are the two groups of macrocyclic lactones?

Avermictins

Milbemycins

What are the avermectins?

Ivermectin, selamectin, eprinomectin, doramectin

What are the milbemycins?

Milbemycin oxim, moxidectin

What is the MOA of macrocyclic lactons?

Ligand gated Cl channel agonist. Binds to GABA or GluCL to increase Cl- concentrations and cause paralysis

How do macrocyclic lactones induce a reduction in motor activity and paralysis?

Paralysis of pharyngeal muscles (no feeding)

Flaccid paralysis

Paralysis of ovijector (nor eggs)

What is the cure for melarsomine toxicity?

Dimercarpol

What benzimidazoles are effective for giardia?

Albendazole

Fenbendazole

Febantel

What is febantel often combined with?

Pyrantel and praziquantel

MOA of ionophores?

Na+ ion transporter

How are macrocyclic lactones used for ectoparasites in cattle?

Pour on or injectable for lice, mites, hypoderma, horn flies

Permethrin is toxic to what animal?

Cats