Antiprotozoal Agents (1) Flashcards
Name 8 antiprotozoal agents
See list
What is the agent of choice for toxoplasma
Clindamycin
Clindamycin MOA
Long term exposure to low levels —> decrease T gondii replication
Affects PR synthesis of free parasites
Impairs tachyzoite infecting host cell
Clidamycin dose
10-20 mg per kg BID or PO
IM 3-6 weeks
Caution with what for Clindamycin
Treating cats with pulmonary TP
Unexplained feline deaths in experimental trial
Clindamycin toxicity
Oral or IM doses at HIGHER doses than for anaerobic infections, for 2-4 weeks
What is FIRST LINE drug of choice for giardiasis
Metronidazole
Metronidazole and cattle
Not allowed!
Metronidazole and trichomonas
Effective! But Not to be used in cattle
Metronidazole MOA
Intermediate metabolites —> affect DNA
Alters Metabolic pathways that are needed for Protozoa survival
Metro toxicity
Dose dependent vestibular toxicity - slowly reversible
Metro use in Food animals
PROHIBITED
No tritrichmonas to in cattle
ELDU in all veterinary species
Triazines (name 2)
Ponazuril
Diclazuril
Ponazuril
Marquis
Diclazuril
Protazil
Triazines MOA
Damages apicoplast of Protozoa organisms (downstream effects unclear)
Triazines — use in poultry
Used as coccidiostat
Triazines- FDA approved treatment and prevention of what
Sarcocystis neurona, horses, PO for 30 days
Triazines toxicity
Horses- blisters (nose, mouth), Rash and hives, Colic, Diarrhea
Is Ponazuril or Diclazuril safer
Literature says P is safer
But not nec true (on market longer)
Nitrothiazoles
Nitrazoxanide= navigator
Nitrothiazoles MOA
Compound —> reduced to FR—> interferes with cellular respiration of TARGET organism
Nitrothiazoles spectrum of activity
FDA approved TREATMENT for s neurona — not prevention though
Nitrothiazoles toxicity
Severe and fatal enterocolitis (can kill normal flora)
Sulfonamides — name 4
Sulfadimetoxine
Sulfadimetoxine with ormetoprim
Sulfadiazine with trimethoprim
Sulfamethoxazole with trimethoprim
SEE CHART OF ANTIPROTOZOAL AGENTS
Memorize chart
Compare Ponazuril vs Nitrazoxanide
Anthelmintic resistance — species
Horse sheep goats = most affected
Cattle in NZ and South America
Mechanisms of anthelmintics Resitance
Failure to reach SOA
Altered target
Inactivation of anthelmintic agent
Resistance to which drugs documented? Which two receive the most attention (although not “true”)
ALL DRUGS
Benzimidazoles and ML “statistically” though
3 methods to reduce resistance
Combine or rotate drugs with diff MOA
Using as few treatments as possible
Use appropriate doses (overestimate the dose if you do not have exact weight???)
Name 6 antinematodal drugs
Benzimidazoles
Levamisole
Pyrantel, Morantel
Heterocyclic compounds (Piperazine, Diethylcarbamazine)
Arsenicals (Melarsomine — heartworm adulticide)
Cyclic Octadepsipeptides (Emodepside)
Benzimidazoles examples
Albendazole, Fenbendazole, others
Benzimidazoles MOA
..see diagram too
Binds to parasite free Beta-tubulin molecules —> affects tubulin polymerization and interfering with cell division, motility , and transport
Inhibits enzymes —> DECREASED energy production in parasites
Benzimidazoles spectrum of activity
..BROAD spectrum (newer agents)
GI nematodes, lung nematodes, some cestodes and treamtodes
Protozoa (giardiasis) (Fenbendazole and albendazole treats giardia in dogs and cats)
Fungi (thiabendazole aka Tresaderm)
Mites
Therapeutic margin of benzimidazoles
Wide
Albendazole toxicity in cats
Weight loss
Neutropenia
Mental dullness
Albendazole toxicity in dogs
Lethargy and anorexia
BM suppression
Liver toxicity (high dose or chronic)
Last two- unknown mechs
Which drug has BM suppression
Albendazole, dogs
When is albendazole contraindicated
Pregnant animals- do not sue in female cattle in first 45 days pregnancy
TERATOGENIC EFFECTS POSSIBLE
Fenbendazole has efficacy against what
BROAD spectrum agent with efficacy against…
Benzimidazoles — herd dosing
Incorporation into water or feed blocks (no direct control!)
Drenching/tubing = time consuming, $
Ruminants devices- special devices that release constant rate of drug, for up to 4 month (animal can be constantly exposed to the drug)
Clinical use of Benzimidazoles in SA
Hookworms, whipworms, tapeworms, TAENIA but not Echinococcus, GIARDIA
Benzimidazoles - clinical use in horses
Fenbendazole-
Large and small strongyles
Pin worms
At higher doses- ascarids
FEBANTEL
Pro drug of Fenbendazole (active metabolite)
IMPT- don’t forget because it doesn’t end in “azole”
Benazimadoles- name two really important ones
Thiabendazole (ineffective against cestodes and trematodes)
FEBANTEL (Pro Drug of fenbendazole!!) only one that doesn’’t end in azole
Benzimidazoles clinical use— WITHDRAWL times
I.e. fenbendazole in cattle vs pigs
Variable, dep on species and formulation
Cattle- 27 days for albendazole, 8 days for fenbendazole
Pigs- 0 days for Fenbendazole
Name 8 Antiprotozal Agents
Pirimethamine Amprolium Clindamycin Metronidazole Triazines (Ponazuril, Diclazuril) Nitrothiazoles (Nitrazoxanide = Navigator ) Sulfonamides/trimetropim Benzimadoles
Pyrimethamine MOA
Normally, Para-aminiobenzoic acid (PABA) is converted by Dihydropteroate synthase into Dihydropteric acid—> Dihydrofolic acid —> via Dihydrofolate reductive —> Tetrahydrofolic acid
Basically Pyrimethamine inhibits Dihydrofolate Reductase —> Less Tetrahydrofolic acid (active form of folic acid)
LESS folic acid synthesis
Folic acid synthesis is important for what
DNA and RNA synthesis
Pyrimethamine spectrum of activity
Toxoplasmosis (dogs and cats)
Neospora (dogs)
Sarcocystis (EPM in horses)
Pyrimethamine toxicity
BM suppression
Pyrimethamine and sulfas
Used in combination with sulfas (sulfadiazine) for 30-180 days
Amprolium MOA
It is a structural analog of thiamine —> competes for thiamine uptake into Protozoal organisms
Amprolium Spectrum of activity
A PREVENTATIVE (vs therapeutic) medication, greatest effect against FIRST generation schizonts
Used in drinking water of poultry and cattle for prevention/treatment of coccidia
Amprolium toxicity
Thiamine deficiency (uncommon)
Thiamine deficiency — PEM in what species
Cattle, goat, sheep
Camelids
Deer
Polioencephalomalacia signs
Star gazing
Anorexia
Loss of motor control
Coma, death
Thiamine deficiency — polyneuritis in what species
Chicken, turkey, pigeons
Polyneuritic clinical signs
Star gazing
Anorexia, paralysis
Death
Amprolium pharmaceutical considerations- labeled for what animals
Labeled for food animals
ELDU in dogs, cats, other animals has occurred
