Anti-Fungal & Anti-Viral Drugs Flashcards
What are fungi? Why is it difficult to develop antifungal drugs?
eukaryotic organisms including yeasts, molds, and mushrooms
they contain few drug targets that are absent in mammalian cells
What do most antifungal drugs used in veterinary medicine target?
ergosterol, an essential component of the fungal cell membrane
What is baker’s yeast?
Saccharomyces cerevisiae specifically used for baking and producing alcoholic drinks
What are the main 4 pathogenic yeasts in domestic animals? When is it most common for animals to become infected?
- Candida albicans
- Candida auris
- Malassezia pachydermatis
- Cryptococcus spp
immunosuppressed state allows yeast in the normal flora to take over
What are the 2 major species of pathogenic yeast of dogs and cats? What do they commonly cause?
- Candida albicans
- Malassezia pachydermatis
- dermatitis on ears and nose
- dandruff with hair loss
What disease does Candida albicans cause in horses and pigs?
Candidiasis of mucous membranes and skin
What 2 yeast are commonly responsible for bovine mastitis?
- Cryptococcus spp.
- Candida albicans
Yeast fungal structures:
What does the selectivity of antifungal drugs based on?
greater affinity for ergosterol than for cholesterol in the animal cell membrane
Mechanisms of action of antifungal drugs:
What 3 antifungals target membrane function? What is their mechanism of action?
- Amphotericin B
- Nystatin
- Natamycin
bind to ergosterol on the cell membrane of fungi, forming transmembrane channels leading to alterations of the cell permeability, resulting in cell death
What 4 antifungals target ergosterol synthesis? What is their mechanism of action?
AZOLES
1. Ketoconazole
2. Itraconazole
3. Fluconazole
4. Terbinafine*
blocks the synthesis of ergosterol via inhibiting fungal cytochrome P450-dependent lanosterol
What is the unique mechanism of action of the azole, Terbinafine?
inhibits squalene epoxidase essential for the conversion of squalene to lanosterol
What is the mechanism of action of Griseofulvin?
inhibits fungal cell mitosis (microtubule formation) and nucleic acid synthesis
What is the mechanism of Flucytosine?
inhibits RNA synthesis in the fungal cell by entering the cell by an enzyme missing in mammalian cells and converting into 5-fluorouracil
What is the mechanism of Caspofungin?
inhibits the enzyme essential for the integrity of the fungal cell wall (human)
What function do Nystatin and Natamysin have on fungi? What is their therapeutic use? What additional use do they have?
fungicidal
yeast infections of the eye, ear, mouth, and GI, especially Candida and Malassezia spp.
- dogs, cats, birds, lizards
feed additive for chickens
What function do Ketoconazole, Itraconazole, and Fluconazole have on fungi? What is their therapeutic use? What else can they be used to treat?
fungistatic
severe mucosal yeast infections in dogs, cats, horses, and birds
hyperadrenocorticism
What function does Amphotericin B have on fungi? What is its therapeutic use? What adverse effect is common?
fungicidal
systemic fungal infections in dogs, cats, horses, and birds
renal toxicity - renal function must be monitored weekly
What is Amphotericin B commonly combined with?
Azoles
- Ketoconazole
- Itraconazole
- Fluconazole
What 2 functions does Terbinafine have?
- fungicidal against dermatophytes
- fungistatic on yeast
- dogs, cats, birds
What function does Flucytosine have on fungi? What 3 species does it most commonly treat?
fungicidal
- Cryptococcus spp.
- Candida spp.
- Aspergillus spp.
What function does Griseofulvin have on fungi? What is it specifically used to treat? Why must use be careful in cats?
slow action fungistatic
dermatophytes - ringworm
can cause leukopenia, anemia, and teratogenesis
What antifungal can be used on psittacines?
Flucytosine
What are viruses?
infective agents typically consisting of DNA or RNA enclosed inside a protein coat (capsid) only able to multiply within living cells using host metabolic machinery
What are the 3 major steps of viral life cycle?
- ENTRY: virus enters cell to utilize its machinery by interacting with special surface receptors
- REPLICATION: virus enters nucleus and replicates
- SHEDDING: virus releases itself from the expired host cell to invade another host cell
What are the 2 major targets of antiviral drugs?
- viral replication enzymes
- viral surface proteins to prevent entry or release
What are the 6 major ways that antivirals inhibit viral replication?
- block attachment to host cells
- block viral entry
- block release of viral genome (uncoating)
- block viral genome replication
- block protein synthesis, processing, or assembly
- block release of new viruses
What are the 3 antivirals used against herpes?
- Acyclovir
- Famciclovir
- Idoxuridine
What antiviral is used against retroviruses?
Zidovudine
What 2 antivirals are used against influenza viruses?
- Amantadine
- Oseltamivir
What 3 antivirals are nucleoside analogs? What is their mechanism of action? What other nucleoside has a unique mechanism of action?
- Acyclovir (purine)
- Famciclovir
- Zidovudine (thymidine)
inhibit viral DNA polymerase
Idoxuridine (false uridine) - prevents viral protein translation from RNA transcripts
What antiviral is a matrix-2 channel blocker? What is its mechanism of action?
Amantadine - binds to M2 protein and blocks its ion channel activity, inhibiting viral uncoating and subsequent replication
What antiviral is a neuraminidase inhibitor? What is its mechanism of action?
Oseltamivir - inhibits viral neuraminidase, blocking viral particles from aggregating and releasing
What interferon is used as an antiviral? What is its mechanism of action?
omega IFN - stimulates an immune response to protect from infection (does not attack virus directly)
Antiviral drugs mechanisms:
What are 5 problems associated with antiviral drugs in animals?
- differences in biological behavior of viruses between human host and animal host
- development of antiviral agents specifically for use against animals viruses is necessary
- available drugs are only virustatic
- host toxicity
- drug resistance
What virus is Amantadine typically used to treat? What adverse effect is common?
equine influenza virus 2
resistance develops quickly
What is Amantadine commonly combined with? What extra therapeutic use does it gain?
opiates or NSAIDs
chronic and neuropathic pain
What 2 antivirals are used to treat feline herpes virus infections? How do they compare?
- Acyclovir - may cause leukopenia, alopecia, or anemia
- Famciclovir - generally well tolerated, may cause anorexia or polydipsia
What antiviral is used to treat feline immunodeficiency virus (FIV) infection? What adverse effects are commonly seen?
Zidovudine
- resistance with long-term use
- anemia
- diarrhea
- weakness
What is the therapeutic use of Idoxuridine? What adverse effect may occur?
herpes keratitis in cats
local irritation of topical administration
What are the 3 therapeutic uses of Oseltamivir?
- some influenza viruses
- canine parvovirus
- prophylaxis for H5N1 influenza in humans
How is omega interferon used in cats and dogs? What adverse effect is seen at high doses?
CATS - calicivirus, FeLV, FIV
DOGS - parvovirus
- fever
- myelotoxicity
- myalgia
