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
