Anthelmintic drugs Flashcards
Benzimidazoles and probenzimidazoles
- Drugs include:
- albendazole, fenbendazole, oxfendazole
- Pro-BZD:
- inactive prodrugs: febantel
- Indications:
- several groups of nematodes, Moniezia
Benzimidazoles and probenzimidazoles
Pharmacodynamics
MOA: Inhibition of microtubule polymerization
- Binding to parasite B-tubulin, which produces subsequent disruption to the tubulin- microtubule dynamic equilibrium
- Alteration of cell division, maintencance of cell shape, cell motility, cell secretion, nutrient absorption, and intracellular transport
- Dissociation rate of BZD form parasite tubulin is much lower than mammalian tubuline
Oral ONLY
Benzimidazoles and probenzimidazoles
Pharmacokinetics in ruminants
- single oral dose, has systemic distribution
- Limited water solubility - affects absorption
- Effect of reduced GI transit time: increased absorption
- Effect on the type of diet:
- binding to fibers produced in “rumen reservoir”
- Liver damage:
- decreased rate of BZD biotransformation and delayed elimination
Benzimidazoles and probenzimidazoles
Pharmacokinetics of non-ruminant species
- Horses:
- oral - reduced bioavailability and shorter residence times
- Cats, dogs, and man:
- oral - only limited rates of dissolution and absorption
- BZ may need to be given at a higher dose or as multiple administrations in order to maintain therapeutic concentrations
- oral - only limited rates of dissolution and absorption
Benzimidazoles and probenzimidazoles
Safety / toxicity
- One of the least toxic of the available anthelmintics
- BZs do not affect microtubule synthesis in animal cells
- Fenbedazole:
- rare vomiting and diarrhea Pancytopenia
- Albendazole:
- teratogenic and embryotoxic in pregnant animals
- BZDs may be toxic to liver and bone marrow in dogs, particularly high doses
- Not recommended for cats
Benzimidazoles and probenzimidazoles
usage:
Albendazole
- Cattle
- liver flukes, tapeworms, GI worms, lung worms
Benzimidazoles and probenzimidazoles
usage
Fenbendazole
- Cattle:
- GI worms, lungworms tapeworms of L4 ostertagia
- Horses:
- strongyles, pimworms, ascarids
- Goats:
- GI worms, lungworms
- Dogs:
- Giardia, roundworms, hookworms, whipworms
- Cats:
- not currently approved for use in domestic cats, but approved for large zoo felines
Benzimidazoles and probenzimidazoles
usage
Oxfendazole
Cattle: Beef and non-lactating dairy
Lungworms, GI nematodes, tapeworms
Nicotinic Agonists - levamisole
Drug class: imidazothiazoles
Indications: Several groups of nematodes
Nicotinic Agonists - levamisole
Pharmacodynamics
MOA: Nicotinic agonsit
- Levamisole is a cholinergic receptor agonist
- Prolonged activation of the excitatory nicotinic acetylcholine receptors on nematode body wall muscle
- Elicits spastic muslce paralysis and prevents egg laying
Nicotinic Agonists - levamisole
Pharmacokinetics
Oral - absorbed in gut and distributed systemically
Nicotinic Agonists - levamisole
Safetly / toxicity
- Low margin of safety; can act on mammalian nAChR
- Both muscarinic and nicotinic effects
- Salivation, defecation, respiratory distress from smooth muscle contration, death
Nicotinic Agonists - levamisole
Usage
Immunomodulatory effects: ruminants
2-3 mg/kg body weight
Improves function of T cells and phagocytes, but not B cells
Activity is sometimes unpredicatable
Nicotinic Agonsits - Pyrantel, Morantel
Drug Class: Tetrahydropyrimidines
Nicotinic Agonsits - Pyrantel, Morantel
Pharmacodynamics
MOA: nicotinic agonist
- Act selectively as agonists at synaptic and extra-synaptic nicotinic Acetlycholin receptors (nAChR) on nematode muscle cells
- Produce contraction and spastic paralysis
Nicotinic Agonsits - Pyrantel, Morantel
Pharmacokinetics
Pyrantel tartrate: well absorbed after oral administration in most species but not in ruminants
Pyrantel pamoate: poorly absorbed form the GI tract
Morantel: Negligibly absorbed in ruminants
Nicotinic Agonsits - Pyrantel, Morantel
Safety and Toxicity
- Pyrantel activates mammalian AChRs with low efficacy
- Salts of pyrantel
- no toxic effects in all animal hosts up to 7x therapeutic dose
- Pyrantel tertrate is slightly less tolerated in horses than pamoate salt
- Pyrantel is not recommended in severely debilitated animals
- Withdrawal periods exist for swine and ruminants
- Avoid combining piperazine and pyrantel/morantel
Nicotinic Agonsits - Pyrantel, Morantel
Usage of Pyrantel
- Horses:
- both salts available
- Dogs
- pamoate
- give with food - delays GI transit time, longer action on GI parasites
- Swine:
- tartrate salt in ration
- Morantel tartrate
- ruminants
Macrocyclic lactones
Two major groups:
Avermectins: Ivermectin, selamectin, eprinomectin, doramectin
Milbemycins: milbemycin oxime, and moxidectin
Macrocyclic lactones:
Pharmacodynamics
MOA: ligand gated chloride channel agonists
- MLs bind to GABA and or GLutamate-gated chloride challens with high affinity
- Increases chloride conductance across cell membranes
- Induce reduction in motor activiry and paralysis in both arthropods and nematodes
- pharyngeal muscles paralysed - interferes with feeding
- Flaccid paralysis - inhibits body movements
- Paralysis of ovijector - inhibits egg laying and reproduction
Macrocyclic Lactones
Pharmacokinetics
injectable: long plasma half life in cattle, long persistency in tissues, long withdrawal periods
Macrocyclic Lactones:
Safety / toxicity
MLs are generally safe, except in MDR -/- dogs
Acute toxic signs include CNS depression, ataxia, and possible death
Emodepside
Drug class: cyclo-octadepsipeptide
Emodepside:
Pharmacodynamics
MOA: latrophilin receptor agonist
- Acts presynaptically on a latrophilin-like receptor of nematodes → inhibitory neuropeptide release → paralysis
- Also may activate calcium dependent potassium channels → K+ influx → Paralysis
- Product:
- topical - cats - against nematodes
Emodepside:
Pharmacokinetics
topical application
rapidly absorbed transdermally
Emodepside:
Safety / toxicity
if orally administered: salivation, vomiting, and mild neurologic effects
Emopdepside:
Usage
Cats: ascarids, hookworms
NO DOG products in the US
Oral administration of cat topical product to dogs for MDR A. caninum is OFF-label
Piperazine
Drug class: heterocyclic compounds
Marrow-spectrum antinematodal
Piperazine:
Pharmacodynamics
MOA: GABA receptor agonist
- Selective agonist of y-amino butyric acid receptors → opening of chloride channels → hyperpolarization of the membrane of the muscle cells of the menatode → flaccid paralysis → removal
- Was previously available for swine, but not currently
Piperazine:
Pharmacokinetics
readily absorbed througn the GI tract and then extensively metabolized
Piperazine:
Safety / toxicity
Almost nontoxic under ordinary circumstances
Large safety margin
Do NOT comine with pyrantel
Piperazine:
Usage
yound dogs for toxocara canis
Melarsomine
Drug class: arsenical
Product: injectable
Melarsomine:
Pharmacodynamics
MOA: not well understood
- arsenic interactions with sulfhydryl groups within cells
- Binding of trivalent arsenic to sulfhydryl groups of proteins or enzymes can disrupt aerobic metabolism in kidneys, liver, and GI tract
Melarsomine:
Pharmacokinetics
rapidly absorbed after IM injection
Acheiving the Cmax at only 8 min post injection
Arsenic plasma levels are higher and measured of a longer time after treatment
Melarsomine:
Safety / toxicity
Overdose: can occur if mg/lb is used instead of mg/kg
Excessive salivation, panting, restlessness, and fever, vomiting, and diarrhea
3x therapeutic dose = death
Dimercaprol is reported in the literature to be an antidote for arsenic toxicity
Diethylcarbamazine Citrate
derivative of piperazine
Used in MDA for lymphatic filariasis along with ivermectin and albendazole in humans
Historically used for D. immitis
Was a microfilaricide, but would induce shock-like symptoms sometimes
Monepantel
Drug class: aminoacetonitrile derivatives
Not available in the US
Sheep formulation
Resistance within 5 years of introduction in Austrailia/NZ
Proziquantel
Drug class: isoquinolinepyrazine
Activity against adults and larval stages of cestodes and trematodes
Proziquantel:
Pharmacodynamics
MOA: Ca2+ channel agonist
- Not completely known, thought to act on voltage gated Ca2+ channels
- Induces a rapid and sustained paralytic muscle contraction
- Induces tegumental disruption
- Metabolic changes - decrease in glucose uptake, glycogen storage, ATP content, and lactate release
- Products:
- oral or injectable
Praziquantel:
Pharmacokinetics
Completely absorbed in the GI tract in most species
Low oral bioavailability in sheep
Praziquantel
Safety / toxicity
overdoses of up to 5x are tolerated without adverse effects
Praziquantel
Usage
dogs and cats: cestodes
Horses, anoplocephala
Epsiprantel
Similar to praziquantel
Epsiprantel:
Pharmacodynamics
MOA: Ca2+ channel agonist
affects Ca2+ homeostasis within the parasite
damages the tegument
Epsiprantel:
Pharmacokinetics
orally: poorly absorbed in the GI tract
Epsiprantel;
Safety / toxicity
prolonged treatments: emesis
Epsiprantel:
Usage
cats and dogs
Clorsulon
Drug class: Benzenesulfonamide
Adult liver flukes in cattle
Clorsulon:
Pharamcodynamics
MOA: metabolic enzyme inhibitor
Competitively inhibit fluke metabolic enzymes
Clorsulon:
Safety / toxicity
Safe drug with hig therapeutic index
Considered safe for use in breeding and pregnant animals
Clorsulon:
Usage
cattle: liver flukes
