Antiparasitics Chapter 12-2 Dr. Dipa Brahmbhatt VMD MpH

Objectives Terminology – antiparasitics MOA antiparasitics Precautions of antiparisitics

Antinematodals Macrolides: Avermectins and Milbemycin Benzimidazole drugs Imidazothiazoles Tetrahydropyrimidines Organophosphates Piperazine compounds

Benzimidazoles MOA: Work by attacking proteins: beta tubulin > cell division Recognize by –azole ending in drug name All can be administered orally, either as a paste, a granulated powder, or a solution and popular equine and cattle species Adv: Cost effective DA: Drug has to be exposed 3-5 days to be effective hence consecutive treatment, teratogenic? SE: are rare with benzimidaloles, but may include vomiting, diarrhea, and lethargy

Benzimidazoles Thiabendazoles – Ascarids and strongyles – Few SE, has anti-inflammatory and antifungal: Tresaderm® (also has dexmethasone and neomycin sulfate) Oxibendazole (Anthelcide EQ Equine Wormer Paste ®) – Equine dewormer – With diethylcarbamazine (daily HW preventative) not used anymore – liver dysfunction

Fenbendazole Fenbendazole (Panacur: dogs/horses/livestock, Safe – Guard: livestock) Wide spectrum of activity (roundworms, hookworms, whipworms, and Taenia pisiformis) – Not used for tapeworms unless species of tapeworm identified – Must be given for 3 consecutive days – Lungworm & Liver fluke: 10 – 14 days Also used to treat metronidazole-resistant giardiasis. SE: include vomiting and diarrhea (no liver problem) Approved for use in lactating dairy animals Panacur® - available in granules, suspensions, and pastes.

Suspension Paste

Benzimidazoles Albendazole (Valbezen suspension) – Cattle: intestinal nematodes, flukes, cestodes and protozoa – Not used in pregnant cows/ dairy cows of breeding age (teratogenic effects and BM suppression) – In companion animals replaced by ivermectin and modern anticestodals Oxfendazole (Benzelmin, Synanthic) – Horses: strongyles, ascarids, pinworms

Antinematodals Macrolides: Avermectins and Milbemycin Benzimidazole drugs Imidazothiazoles Tetrahydropyrimidines Organophosphates Piperazine compounds

Tetrahydropyrimidines MOA: Mimics ACh and cause initial stimulation then paralysis of the worm Effective against roundworms (ascarids, pinworms, strongyles) and hookworms pyrantel pamoate Examples include pyrantel pamoate, pyrantel tartrate, and morantel tartrate Also OTC (pipa tabs are more popular) Heartguard plus (ivermectin), Drontal (praziquantel), drontal plus (bemzimidazole: febantel and praziquantel) Adv: Very safe, pleasant taste Nemex®, Strongid-T® Suspensions mix well

Antinematodals Macrolides: Avermectins and Milbemycin Benzimidazole drugs Imidazothiazoles Tetrahydropyrimidines Organophosphates Piperazine compounds

Piperazine – MOA: Blocks neuromuscular transmission > paralyses parasite – Effective only against ascarids – Clients should be made aware that piperazines often result in intact worms being vomited or passed in stool (infectious) – Don’t kill tapeworms, whipworms, hookworm, protozoa: narrow spectrum – Practically nontoxic – Sold OTC Hartz Health Measures Once-a-Month Wormer® for Puppies Pipa-Tabs®

Antinematodals Macrolides: Avermectins and Milbemycin Benzimidazole drugs Imidazothiazoles Tetrahydropyrimidines Organophosphates Piperazine compounds

Organophosphates MOA: Inhibit cholinesterase activity, causing ACh to remain active in the neuromuscular junction > parasite paralysis Used on agricultural products (before nerve gas: warfare) Are neurotoxic to parasites; some cause neurologic side effects in the host Both endoparasitic and ectoparasitic (mostly used for) Narrow range of safety; not for use in heartworm-positive dogs (dyspnea & death, sudden worm kill off) Effective against bots and a variety of nematodes Dichlorvos Dichlorvos (Task®) Not safe to use OPs off-label!!! Treat with atropine / glycopyrrolate during overdosage

Side Effects of Organophosphate Poisoning Salivation Lacrimation Urination Dyspnea Defecation Emesis Also ataxia, anxiety, abdominal pain, muscle tremors, pupillary constriction, seizure, hyperexcitability

Antinematodals Macrolides: Avermectins and Milbemycin Benzimidazole drugs Imidazothiazoles Tetrahydropyrimidines Organophosphates Piperazine compounds

Imidazothiazoles Work by stimulating the nematode’s cholinergic nervous system, leading to paralysis of the parasite (therefore, not ovicidal) Effective against ascarids, strongyles, whipworms, and hookworms Was used as a microfilaricide in the past levamisole (Levasol®) An example is levamisole (Levasol®) – Expels most nematodes in 24 hours (some may be passed alive) – Available in oral forms such as pellets, powder, suspensions, and pastes – Also has anti-inflammatory and immunostimulant properties – May cause toxicity in host animal due to cholinergic effects

Anticestodals Cestodes = “Tapeworms” – Scolex, neck, proglottids – Scolex attaches to intestinal wall – Goal = scolex detachment Some anticestodals are used in combination with antinematodal drugs.

ANTICESTODALS Praziquantel Epsiprantel Fenbendazoles

Anticestodals Praziquantel (Droncit®) Praziquantel (Droncit®) – MOA: Works by increasing the cell membrane permeability of the cestode, – Owners will not see tapeworm or segments passed after treatment – Works on all cestode species: Taenia, Dipylidium caninum, Echinococcus spp. zoonotic – With Dipylidium caninum, it is especially important to also eradicate fleas to prevent reinfection. – Available as oral tablet or injectable – Not ovicidal (eggs) – Side effects are rare; include anorexia, vomiting, diarrhea, and lethargy (INJECTABLE)

Anticestodals Epsiprantel (Cestex®) Epsiprantel (Cestex®) – Effective against Taenia spp. and Dipylidium caninum, but not Echinococcus spp. (wild carnivores, severe liver disease humans) – Like praziquantel, disintegrates cestode so that it can be digested by host – Unlike praziquantel, not absorbed well by GI tract, so systemic side effects are minimal. Fenbendazole Fenbendazole – A benzimidazole (covered previously – antinematodals) – Effective against Taenia spp. but not Dipylidium caninum – Unless other parasites are present in animal that can be treated with fenbendazole, praziquantel or epsiprantel are recommended.

Anticestodals DroncitCestexFenbendazole IngredientPraziquantelEpsiprantelPanacur MOA Permeability of cell (Ca) Disrupt cell division Stages SpeciesAll Taenia Dipylidium Echinococcus Taenia spp Dipylidium caninum Taenia spp FecesNo worms SEAnorexia, v/d, lethargyLessv/d Dipylidium: needs proper flea controlZoonosis

Antitrematodals Clorsulon (Curatrem®) Clorsulon (Curatrem®) – A benzene sulfonamide – Works by inhibiting the trematode’s enzyme systems for energy production (robs fluke of energy) – Effective against Fasciola hepatica Adult and immature forms – OTC – Drench – Not recommended in dairy animals – Ivomec plus: clorsulon + ivermectin – Increases spectrum of activity – Increases withdrawal time – Can’t use in female dairy cattle of breeding age

Antitrematodals Albendazole (Albazen®) Albendazole (Albazen®) – Benzimidazole that interferes with the energy metabolism of the worm – Also effective against some nematodes (broad- spectrum) – Not approved for use in lactating animals Praziquantel Praziquantel – Covered previously (anticestodal) – Also effective against lung flukes in dogs and cats

Drontal Plus® Contains: – Febantel, a probenzimidazole that is metabolized in the animal to a true benzimidazole. Effective against ascarids, strongyles, and pinworms – Pyrantel pamoate Antinematodal – Praziquantel Anticestodal Antitrematodal

General Drontal/ Drontal + PanacurPyrantel Pamoate Ivermectin Hooks*** Rounds*** Tapeworm** Whipworm** Demodex* Scabies* Giardia* Ear mites* Dog Kidney worm * mff*

VibrantelPyrantel Pamoate PanacurCestexDroncit/ Drontal + Toxocara Canis*** Toxocara Leonina*** Ancylostoma Braziliense ** Ancylostoma caninum *** Uncinaria Stenocephal *** Trichuris Vulpis* Trichuris Campanula* Dipylidium Canninum** Taenia Pisiformia**** Echinococcus Granulosus *** Echinoccocus Multiocularis **

Antiprotozoals Protozoa: coccidia, Giardia, Sarcocystis neurona: EPM Coccidiosis is a protozoal infection that causes intestinal disorders – Hygiene and sanitation important Most anticoccidial drugs are coccidiostats (do not actually kill the parasite, so hygiene is crucial) Sulfadimethoxine (Albon®) Sulfadimethoxine (Albon®) – Reduces the number of oocysts shed, thus reducing spread of disease Ponazuril (Marquis®) - EPM Ponazuril (Marquis®) - EPM – Equine antiprotozoal oral paste ; used off-label in dogs/cats – Kills coccidia – Given in 3 doses – days 1, 2, and mg/kg of a 50 mg/mL solution 30 mg/kg of a 50 mg/mL solution Others (work mainly by affecting the protozoan’s metabolism) – Nicarbazine, Amprolium: calves high doses can cause thiamin deficiency, Monensin (DON’T USE IN HORSES), Decoquinate, Robenidine Coccidia – carnivore – Isospora spp Coccidia – herbivores - Eimeria spp

Antiprotozoals Giardiosis is a protozoal disease caused by Giardia spp. – Antiprotozoal drugs Metronidazole (Flagyl®) (enters the protozoal cell and interferes with its ability to function and replicate). IBD. SE: Neuro Benzimidazoles Fenbendazole (Panacur®): Giardia in pregnant and lactating animals Albendazole (Valbazen®): Giardia but SE: leukopenia so not favorable – Giardia Vaccine (GiardiaVax®) Blood protozoan Babesia sp. is transmitted by ticks – Imidocarb – Imidocarb (injectable) has cholinergic effects on the protozoan (not used in food animals) – Tick prevention also important

References Romich, J.A. Pharmacology for Veterinary Technicians, 2 nd edition Bill, R.L. Clinical Pharmacology and Therapeutics for the Veterinary Technician, 3 rd edition