Antifungals, Antiprotozoals, Antivirals, Paraciticides Flashcards
What are the mechanisms of action of the antifungal agents?
- Amphotericin B binds ergosterol to form pores
- Azoles inhibit ergosterol synthesis
- Griseofulvin and Fenbendazole bind microtubules to inhibit mitosis
What are the mechanisms of action of the antiprotozoal agents?
- Folate acid synthesis inhibitors: Blocks successive steps in folate synthesis of protozoa needed for protein/NA metabolism
- Metronidazole: reduced metabolite causes breakage of DNA
- Clindimycin: binds 50s ribosome to disrupt protein synthesis
- Amprolium: Thiamine analog
- Ponazuril: Activity against important organelles
- Nitazoxanide: Interferes with pyruvate:ferrodoxin oxidoreductase enzyme (PFOR) essential for anaerobic energy reactions (same pathway that metronidazole requires)
What are the mechanisms of action of the antiviral agents?
- AZT: inhibits reverse transcriptase
- Purine nucleoside analogs: Analogue of guanosine- inhibits viral DNA polymerase
- L-lysine: competes with arginine, herpesvirus needs to make proteins
What are the most important side effects of the antifungal agents?
- Amphotericin B- Very Nephrotoxic, acute anaphylactic reactions
- Azoles- GI (mild) and rare hepatotoxicity
- Griseofulvin- Common, Cats most serious side effects: neutropenia,
anemia, neurotoxicosis - Fenbendazole- OFF LABEL use for dermatophytes in LA
What are the most important side effects of the antiprotozoal agents?
- Folic Acid Synthesis Inhibitors: Bone marrow suppression, Keratoconjunctivitis sicca, teratogenic
- Metronidazole: Carcinogenic/mutagenic! BANNED FOOD ANIMALS!
- Clindimycin: DO NOT USE IN HORSES,RUMINANTS, RODENTS,
LAGOMORPHS- Serious GI side effects that can cause death - Amprolium: Thiamine deficiency Polioencephalomalacia high doses
- Ponazuril: Few
- Nitazoxanide: disrupts normal GI flora, some deaths caused by
enterocolitis reported, laminitis
What are the most important side effects of the antiviral agents?
AZT:cats–anemia
What are the distinguishing differences in the pharmacokinetics of the antifungal agents?
- Amphotericin B not water soluble- IV or topical only
- Azoles- oral or topical
- Griseofulvin accumulates in keratin (skin, nails, etc), need to administer for extended lengths for effect
What are the spectrum of activity of the anti fungals?
Amphotericin B is most effective against all EXCEPT ringoworm (dermatophytes), Azoles have wide spectrum, Griseofulvin DERMATOPHYTES ONLY, Fenbendazole OFF LABEL for dermatophytes in Large Animals
What are the major indications for use for the anti-protozoal agents?
- Folic acid inhibitors: aerobic organisms
- Metronidazole: anaerobic only, Entamoeba, Trichomonas, Giardia
- Clindimycin: Toxoplasmosis
- Amprolium: Coccidiosis in food animals
- Ponazuril: Sarcocystis neurona horses (EPM), off label SA coccidiosis
- Nitazoxanide: EPM in horses
What are the indications for use of antivirals?
- AZT: retroviruses (FIV, FeLV)
- Purine analogs: Herpesviruses
- L-lysine: cats with Herpes conjunctivitis
Which antiviral agent is not a drug?
L-lysine is a nutritional supplement
What drug should you use to treat a nematode infection?
Fenbendazole (Benzimidazole), Pyrantel (nicotinic anthelmintic), Ivermectin (Macrocyclic Lactone)
What drug should you use to treat a trematode infection?
Fenbendazole (Benzimidazole)
What drug should you use to treat a cestode infection?
Praziaquantel (Isoquinolone)
What drug should you use to treat a flea infestation?
Permethrin (Synthetic pyrethroids), Fluralaner (Isoxazolines)
What drug should you use to treat a tick infestation?
Permethrin (Synthetic pyrethroids), Fluralaner (Isoxazolines)
What drug should you use to treat a mite infestation?
Ivermectin (Macrocyclic Lactones), Permethrin (Synthetic pyrethroids)
What should you use to treat a bot infestation?
Ivermectin (macrocyclic lactone)
What is the MOA of the Benzimidazoles?
- Bind to and inhibit tubulin
- Inhibit mitochondrial enzyme function
What is the MOA of the Macrocyclic lactones?
Causes FLACCID PARALYSIS in 2 ways:
1.Hyperpolarize parasite neurons
2.At synapses enhance release of GABA
What is the MOA of the Nicotinic anthelmintics?
Cause ACh release, Continued depolarization
RIGID paralysis
What is the MOA of the Isoxazolines?
Acts at neuron chloride channels
RIGID paralysis
What is the MOA of the Isoquinolones?
Isoquinolones 2 MOAs:
1- Destroy cestode tegument
Exposes parasite antigens so Host’s GI/immune system destroy worm
2- Paralyze the parasite- RIGID paralysis
What is the MOA of the Synthetic pyrethroids?
Acts @ presynaptic sodium channels
RIGID paralysis
What are the parmacokinetic factors to consider when using Parasiticides?
Fluralaner Long 1/2 life- longer duration between oral treatments-~12 wks
What are the major adverse effects, contraindications and safety features of the Benzimidazoles?
Adverse effects uncommon- high margin of safety
Safe for use during pregnancy
Hypersensitivity reaction
Antigens released by dying parasites
What are the major adverse effects, contraindications and safety features of the Macrocyclic lactones?
Hypersensitivity reaction- Antigens released by dying parasites
Neurologic signs if crosses blood brain barrier
Sensitivity in collie & herding breeds- p-glycoprotein
What are the major adverse effects, contraindications and safety features of the Nicotinic anthelmintics?
Adverse effects uncommon- good safety margin
Poorly absorbed from GI tract (Added safety)
Possible vomiting
What are the major adverse effects, contraindications and safety features of the Isoxazolines?
Neurologic including Seizures*
*Do not use in patients with history of seizures
Gastrointestinal
What are the major adverse effects, contraindications and safety features of the Isoquinolones?
Adverse effects uncommon- Wide margin of safety
Possible gastrointestinal upset
Injectable formulation: pain with injection
What are the major adverse effects, contraindications and safety features of the synthetic pyrethroids?
Relatively safe for most mammals
EXCEPTION: TOXIC for CATS Metabolized via glucuronidation in liver
Note: OK to use products specifically labeled for cats
Toxicity - Neurological signs
