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50 Cards in this Set
- Front
- Back
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Fluroquinolones
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Addition of a fluoride atom to the quinolone structure resulted in the creation of _________, which gave greater absorption, better antibacterial activity, and reduced toxicity.
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Fluoroquinolones
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Target of action: directly inhibit nucleic acid/DNA synthesis
Bacteri-: Rapidly bactericidal but CONCENTRATION dependent!!! --> results in damage to bacterial DNA and leads to bacterial cell death Admin: variety Toleration: Well tolerated by animals Resistance: Chromosomally mediated Spectrum: Highly active against Gram-, lower activity against Gram+ aerobes, active against all aerobic enteric Gram- bacilli and all aerobic bacterial gut pathogens, active against 90% of bacteria isolated from urine, and active against Bruceela, Chlamydophyla, Mycobacterium, and Mycoplasma (aka. Active against Gram- and Gram+ pathogens affecting skin, respiratory, and urinary tract infections) Distribution: large volume of distribution, good penetration into CNS, CSF, bone and cartilage; found in milk of lactating animals Absorption: rapidly absorbed after oral admin in monogastrics - food may delay absorption Excretion: renal excretion - crystals may form in concentrated acidic urine Examples: Ciprofloxacin, Enrofloxacin, and Marbofloxacin |
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The only class of antimicrobial agents in clinical use that are DIRECT inhibitors of bacterial DNA synthesis.
What two bacterial enzymes does this class of antimicrobial agents inhibit? |
Fluroquinolones
DNA gyrase and topoisomerase |
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Clinical uses of fluroquinolones
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-UTIs caused by Pseudomonas
-Bacterial prostatisis in dogs -Osteomyelitis by Gram- aerobes -Saprophytic Mycobacterium infection in cats (feline leprosy) -Deep granulomatous pyoderma -Ototis externa caused by Gram- infections -Bovine respiratory disease complex Should not be used routinely for small animal infections! Too irritating to give i/m in horses! |
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Is extra-label use of fluroquinolones allowed in food animals? (AMDUCA)
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No! It is prohibited!!
If used in horses must be non-food! |
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Adverse effects of Fluroquinolones
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-Uncommon, normally GIT upset
-Inhibit GABA and stimulate NMDA receptors, with potential for CNS effects; increased likelihood when used in combo with NSAIDS -Acute retinal degeration in cats treated with enrofloxacin --> blindness -Should NOT be used in young growing animals because it causes erosion of joint cartilage (if must use them, supplement chondroprotectants) |
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Baytril
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-An enrofloxacin
-Authorized in UK/ROI in dogs, cats, poultry, cattle, pigs -For dogs: treatment of bacterial infections of the alimentary, respiratory, and urogenital tracts, skin, secondary wound infections, and otitis externa -For cattle and pigs: diseases of the respiratory and alimentary tract of bacteria or mycoplasmal origin and secondary bacterial infections to viral conditions; Atrophic rhitinis and enzootic pneumonia in pigs |
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Glycopeptides
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Target of action: Prevent cell wall synthesis and inhibit bacterial cell permeability
Bacteri-: Teicoplanin and Vancomycin bactericidal to most Gram+ as well as penicillinase-producing Staphylococcus Resistance: most Gram- are resistant. |
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Vancomycin
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Type of antimicrobial: Glycopeptide
Admin: Must be given i/v pump infusion over 60 min as it causes tissue damage and is poorly absorbed PO Excretion: via the kidneys Clinical use: treats multi-drug resistant infections (drug of last resort), but has limited use in Vet Med because it is $$$ and there is no authorized Vet drug. Has been used to treat MRSA and enterococcal infections in horses Adverse effects: Highly irritating! If given rapidly i/v, causes anaphylactic-type reaction. Potentially nephrotoxic |
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Bacitracin
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Type of antimicrobial: Peptide
Target of action: inhibits the formation of the bacterial cell wall by complexing directly with pyrophosphate carrier and inhibiting dephosphorylation required for regeneration Spectrum: Gram+ bacteria Absorption: NOT absorbed from GIT Adverse effects: causes nephrotoxicity if given parenterally Admin: topical, orally in poultry and pigs Clinical uses: pigs/poultry- growth promotion and treatment of enteritis (banned from use as a feed additive/growth promoter in EU) |
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Polymixins
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Type of antimicrobial: peptide
Action: surface active agents - disrupt the cell membrane phospholipid and increase cell membrane permeability Spectrum: Gram- more sensitive than Gram+, active against Pseudomonas aeruginosa Adverse effects: nephrotoxicity and ototoxicity if given parenterally Admin: topically or opthalmically, usually used as a combo Example: Surolan |
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Nitrofurans
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Spectrum: Broad, Gram- and Gram+
Uses: secondary treatment for Giardia -Banned in food animals!!! -Carcinogenic!!! |
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Nitroimidazoles
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-Antiprotozoal and antibacterial activity
-Only for use in companion animal practice!!! -Examples: metronidazole |
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Metronidazole
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Bacteri-: bactericidal to anaerobic bacteria
Action: causes bacterial cells to break down into unstable intermediates, cause extensive damage to bacterial DNA and inhibits DNA repair enzyme (DNAase-1) Requires anaerobic conditions!!! Antiprotozoal as well!!! Absorption: well absorbed from GIT, especially after food in dogs Distribution: Distributed to most body tissues and fluids, including bone, abscesses, CNS, and seminal fluid. Extensive metabolism in the liver. Excretion: 60% in urine Clinical uses: GIT infections (Giardia, Entamoeba, protozoal infections), mouth infections (combo with Spiramycin), bacterial overgrowth in SI and for antibiotic response diarrhea, anaerobic soft tissue infections Adverse effects: uncommon, dose-related neuropathy in dogs, cats salivate profusely after admin, inappetence in horses, carcinogenic effect (led to ban in FA), may be teratogenic!! NO VET MED drug authorized in USA, Canada!!! |
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Rifampicin/Rifampin
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Bacteri-: bactericidal
Action: inhibits RNA polymerase- prevents transcription of DNA to RNA Resistance: chromosomal mutation leading to resistance occurs at a high rate in most bacteria Spectrum: Gram+ aerobes, particularly Staphylococcus, Brucella, Mycobacterium tuberculosis Admin: oral, i/v Absorption: rapid from GIT in calves, dogs, horses Distribution: widely distributed to the tissues, milk, bone, CNS, and soft tissues Excretion: primarily by liver Adverse effects; metabolism of other drugs may be affected, causes red staining of body fluids, hepatic effects (greater level of toxicity in dogs than in humans), elevated liver enzymes/liver damage Clinical uses: dogs- treat chronic granulomatous skin conditions; horses- in combo with erythromycin to treat Rhodococcus equi in foals |
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Targets for antifungal therapy
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Cell membrane (using ergosterol), DNA synthesis, and cell walls
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Amphotericin B
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Type: A polyene antibiotic
Action: bings to ergosterol on the fungal cell membrane, disrupting cell membrane stability --> cell death Spectrum: effective against a broad range of filamentous fungi, has an immunomodulatory effect Clinical applications: initial treatment of choice for rapidly progressing systemic mycoses and cryptococcal meningitis, mycotic GI disease (where vomiting prevents oral drugs), treatment of histoplasmosis, blastomycosis, cryptococcosis, coccidiomycosis, candidiasis, sportotrichosis, and pythiosis Admin: parenterally, i/v Distribution: binds to cholesterol-containing membranes in tissues, liver, kidney, will cross inflamed pleura and synovium Adverse effects: cumulative dose-related nephrotoxicity (up to 80% of dogs show this), nausea, fever, anorexia |
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Azole antifungals
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-Have become the initial treatment of choice for all but the most rapidly progressing systemic fungal infections (work more slowly than Amphotericin B)
-Imadazoles are potent inhibitors of mammalian cell cytochrome P450 -Decreased synthesis of testosterone, cortisol, cholesterol, and androgens may occur during admin -Some are immunosuppressant |
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Ketoconazole
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Type: Azole antifungal
Indications: systemic treatment of otitis and dermatitis caused by Malassezia spp, infections caused by Candida spp and Microsporum canis Absorption: variable, recommended to be given with food Distribution: penetrates poorly into protected areas (CNS, anterior chamber of eye, prostate) Excretion: primarily hepatic metabolism Adverse effects: great potential for adverse effects. Nausia, anorexia, and vomiting more frequent at high dosages. Pruritis, alopecia, lightening of coat, weight loss during long-time therapy of oral admin. Cats more sensitive to hepatic damage. Teratogenic!! Inhibits cortisol production. is a Pgp efflux pump inhibitor. |
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Enilconazole
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Type: Azole antifungals
Admin: topical Indications: treatment of dermatomycoses (ringworm) in cattle, horses, and dogs by Trichophyton and Microsporum spps. Adverse effects: hypersalivation, idiopathic muscle weakness and slightly elevated ALT concentrations reported in cats. Vomiting when used as intranasal infusion in dogs. Potentially carcogenic in humans |
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Micronazole
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-Used for topical yeast infections, superficial dermatophytes, and as intrasal infusion in nasal aspergillosis
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Fluconazole
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-Treatment of choice for cryptococcus CNS infections
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Griseofulvin
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Action: fungistatic drug --> controls it, doesn't kill it
Indications: Treatment of dermatophytic infections of hair, skin/claws of dogs, cats, horses from Thrichophyton or Microsporum spps. Absorption: irregular - enhanced by fatty meal Deposition: In keratin precursor cells & is concentrated in the stratum corneum of the skin, nails, and hair, thus preventing fungal invasion of newly formed cells (stratum corneum grows out ~6 wks. Effectively the ringworm grows out) Adverse effects: vomiting, diarrhea, anorexia more often in cats than dogs. Bone marrow suppression in kittens (<8wks). Hepatotoxic in cats after long-term admin. May be teratogenic! Adverse rxns more common in certain breeds of cats (Himalyan, Persian, Siamese) |
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4 types of bacterial resistance strategies
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-Reducing entry of antimicrobial agents
-Expulsion of antimicrobial agents -Inactivation of antimicrobial agents -Modification of antimicrobial targets |
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Three mechanisms of horizontal transfer of genetic material
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Conjugation- transmission of resistant genes via plasmid (bacterial circular DNA) exchange. Allows resitance to spread among a population of bacterial cells much faster than a simple mutation and vertical evolution would permit
Transduction- a virus serves as the agent of transfer between bacterial strains Transformation- DNA released from a bacterium is picked up by a new cell. After the new DNA is incorporated into the cell, it results in the emergence of a new, resistant genotype |
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What is the principle driver of resistance?
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Widespread exposure to antimicrobials of multiple, often non-pathogenic bacterial species carried by the host. Exposure acts as a selection pressure, increasing the survival of resistant strains as a percentage of the host's microbial load.
Total population of that bacterium tends to revert to the susceptible form in the absence of continued exposure of antimicrobials |
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Examples of problematic antimicrobial use in Ireland
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-Poultry: to improve growth rates and to treat welfare problems because husbandry is poor
-Pigs: medicated feed commonly given longer than prescribed because they mixed it in to the food -Cattle: prescribing without knowing causal agent, failure to complete full course to shorten AM withdrawal time -Companion animals/equines: inappropriate selection (based on $, convenience, owner pressure), prophylaxis in sterile surgery |
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Practices to decrease AMR
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-Targeted vaccination and immune system supports
-Improved husbandry -Better biosecurity -Resisting inappropriate use caused by owner pressure, $ pressure -Never prescribe AMs without doing an exam and diagnosis -Pay attention to new and critically important AMs -Avoid off label use whenever possible -Recorded use of AMs - both vet and farmer equally responsible for not making steps to reduce AMR in Netherlands -Spread the word, alert clients |
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Selectivity of Antiparasitics
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-Need a drug at site of action long enough to be effective but short enough for safety
-Be aware of environmental concerns -Must distribute to appropriate tissues to be taken up/absorbed by the organism so that therapeutic concentration can be achieved in the parasite -Need to know stage of parasite to ascertain presence of target and/or where the stage is in the host -Need to exploit physical and pharmacological differences btw host and parasite (different organisms have different synapses |
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What causes resistance to anthelmintics?
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-Same anthelmintic, same animals, same fields
-Underdosing (transdermals/pour-ons especially) -Misdiagnosis leading to overuse |
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Known for their remarkable overall safety
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Benzimidazoles
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Benzimidazoles
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-Treats nematode and trematode infections in domestic animals
-Spectrum is broad with activity against nematodes, trematodes, lungworm, and cestodes. Active against immature stages. Ovicidal -Wide development of resistance -All bind to beta-tubulin, leading to unfolding of protein --> lethal in rapidly dividing cells (starves the parasite) -Has to absorb and distribute through the target tissues of host and then has to absorb and distribute through the parasite -Absorption from GIT poor, improved with co-admin of a fatty meal -Difference in the rate and extent of absorption depend on spp, dosage, formulation, solubility, and operation of the esophageal groove reflex -Cuticle diffusion predominant pathway for anthlemintics (nematodes = cuticle) -The rumen acts a drug reservoir, slowing transit time through abomasum, allowing it to be better absorbed in the SI -Enterohepatic recycling- continuous re-exposure of gut parasites -Adverse effects: high doses can damage hemapoietic cells (RBCs, WBCs), intestinal epithelium, hair growth. Some have potential to be teratogenic (dose dependent and only at certain times of embryogenesis |
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Albendazole
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Effective against adult and immature helminths, cestodes (heads and segments), adult liver fluke
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Fenbendazole
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-Suspension for oral admin in cattle, sheep, and goats to kill helminths, cestodes and flukes
-Important therapeutic in dogs as granules, tablets, and pastes -Used extralabel in dogs to treat Giardia -Does NOT treat heartworm or echinococcus -Panacur -Adverse effects = bone marrow suppression and thromboischaemic pinna necrosis in companion animals |
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Febantel
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-A pro-BSD compound, metabolized to fenbendazole and oxfendazole
-Used in ruminants, horses, dogs, cats, and pigs -Dogs and cats require 3 days treatment -AE: cats more likely than dogs to demo vomiting and diarrhea |
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Triclabendazole
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-Narrow spectrum
-Most widely used FLUKICIDE -Excellent efficacy against adult and immature flukes -NOT active against RUMEN FLUKES!!! -Does NOT act on tubulin in nematodes, but possibly targets another tubulin site in flukes -Oral admin -AE: unsteady gait, dullness, reduced appetitie for 1-3 days -Not permitted for using in milking cows for human consumption |
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Levamisole
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-A worldwide imidothiazole
-Acts selectively as a nicotinic acetylcholine agonist at synaptic and extrasynaptic nicotinic acetylcholine receptors on muscle cells -Spastic paralysis of susceptible nematodes -Bioavailability greatest with parenteral injection -Admin: parenteral injection (s/c), oral, topical pour-on -90% of total dose excreted in 24 hrs -Broad spectrum activity against mature stages of major GI nematodes, and mature and larval stages of lungworm in cattle and sheep -AE: muscarinic and nicotinic effects in host (salivation, defecation, respiratory distress), death, more likely when given parenterally -Not recommended for horses and not for animals from which milk or eggs are produced from human consumption |
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Tetrahydropyrimidines
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-Pyrantel and Morantel
-Used as a broad spectrum anthelmintic in sheep, cattle, pigs, horses, dogs, cat -In horses = Treats infections of large strongyles, pinworms, large roundworms, small strongyles -Pigs = treats large roundworms and Oxyuris -Cattle/sheep = antinematodal -Dogs/cats = ascarids -Act selectively on parasitic nicotinic acetylcholine receptors -Often combined with Febantel for increased activity against Ancylostoma and Trichuris in dogs, and combined iwth ivermectin for heartworm treatment -AE: ataxia occasionally seen in cattle when given high doses |
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Used for treatment of Toxocara and Toxascaris
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Piperazine
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Macrocyclic Lactones
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-Include Avermectins and Milbemycins
-Effective against nematodes (gut and lung) and arthropods -Will NOT kill eggs -Well absorbed when admin PO or parenterally -Concentrate in adipose tissue -A single dose can persist in concentrations sufficient to be effective for prolonged periods in protection by some nematode and arthropod spp (several weeks) -AE: collie breeds show signs of toxicity (ataxia, depression, salivation, mydriasis, coma, death) |
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Macrocyclic Lactones in Cattle
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-Ivermectin, moxidectin, doramectin, abamectin
-Oral, s/c, and pour-on -Effective against sucking lice and warbles -Elimination through milk - most not recommended for use in animals that produce milk for human consumption |
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Macrocyclic Lactones of Sheep/goats
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-Ivermectin, moxidectin, doramectin
-Oral, s/c and i/m -High efficacy against all stages -Development of resistance is a serious issue -Effective against sheep scab and nasal bots |
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Macrocyclic Lactones of Pigs
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-Ivermectin and doramectin s/c or ivermectin is given in feed for 7 days
-Treatment of all adult and larval stages of the common swine parasites, including the kidney worm -Treats mange and lice -~80% efficacy against Trichuris suis - |
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Macrocyclic Lactones of Horses
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-Ivermectin and moxidectin
-Oral -Effective against broad range of adult and migrating larval stages of nematode (large and small Strongyles included) and arthropod parasites -Resistance is emerging |
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Macrocyclic Lactones of Dogs/cats
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-Ivermectin, selamectin, moxidectin
-Topical, moxidectin as injection also -Prevention of heartworm disease and control of GI roundworms -Fleas relatively insensitive to invermectin -Selamectin and moxidectin are true endectocides - activity encompasses common intestinal nematodes (Toxocara), heartworm, and external parasites (fleas, biting lice, and mites) |
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Taeniafuges
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Interfere with tapeworm ability to maintain in location in gut
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Bunamidine
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-Taeniacidal
-Admin: oral -Anthelmintic activity reduced in presence of food -Crushing tablets increases absorption, but also adverse effects -Disrupts tapeworm's tegument, increasing glucose efflux -Scolex may survive!!! Major action exerted on proglottids -AE: vomiting and diarrhea most frequent, liver damage, ventricular fibrillation |
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Praziquantal
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-Drontal/Droncit
-Safe, highly effective anticestodal -Taeniacidal -Recommended for treatment of all the common tapeworms in cats and dogs -Also effect against tapeworms in horses and ruminants -Rapidly absorbed after oral admin and is improved if given with a meal -Efficacy can be REDUCED by concurrent use of corticosteroids, phenytoin or carbamazepine -AE: Vomiting (prevents overdosage), excessive salivation in cats |
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Emodepside
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-Profender
-Effective against a number of gastrointestinal nematodes, Toxocara cati, Toxascaris leonina, and Ancylostoma tubaeforme -Licensed as a drug combo with praziquantel -Inhibition and flaccid paralysis of pharyngeal and somatic musculature of nematodes (they get paralyzed, starve and get passed out) -Relatively safe |
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Melarsomine sodium
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-Contains ~15% trivalent arsenic
-Safer than thiacetarsamide -Greater efficacy in killing adult heartworm -Initial injection one month, then one month later give Injection into lumbar epaxial muscle, 2 doses, alternate sides, 24hrs apart -90% male, 10% female heartworm killed with single injection -AE: risk of pulmonary embolism if not properly staged -Give Doxycycline during 1st or 2nd month following infection --> lethal to third and fourth stage heartworm larvae |
