Antifungals & Antivirals Flashcards
Which are the factors involved in the therapeutic failure or relapse after antifungal therapy?
*Most antifungals are fungistatics, so clearance of the infection relies mainly on the host response
*Poor penetration into the foci of infection
*Intrinsic and acquired resistance to antifungals
*Toxicity
*Inappropriate dosage regimens
*Antifungal culture and susceptibility testing methods not well developed
How long does it take to see full clinical effect of antifungals?
?
Which antifungal is considered fungicidal?
Amphotericin B
Which antifungal is indicated for treating systemic fungal infections?
Amphotericin B
Which antifungal induces hepatic metabolizing enzymes?
Griseofulvin
Which antifungal inhibits hepatic metabolizing enzymes?
Ketoconazole
Which antifungals are nuclear-directed?
Griseofulvin
Flucytosine
Which antifungals are cell membrane directed?
The Polyenes
The Azoles
Others
What are the two major classes of antifungals?
Cell membrane directed
Nuclear directed
What is the MOA for griseofulvin?
Fungistatic
Interacts with microtubules to disrupt the function of the mitotic spindle
(Obvs)
What is the spectrum of activity for griseofulvin?
ONLY dermatophytes
(E.g. microsporum, trichophyton, epidermophyton)
Griseofulvin is reported to be ____ and _____.
Teratogenic and carcinogenic
_____ has a selective toxicity based on an energy dependent uptake preferentially into fungi vs mammalian cells.
Grieseofulvin
Signs of griseofulvin toxicity (8)
Diarrhea
Depression
Anorexia
Hepatotoxicity
Bone marrow suppression
Ataxia
Skin rash
Photosensitization
What breeds of cat are especially sensitive to skin rash/photosensitization from griseofulvin toxicity?
Persian
Siamese
Abyssinian
Absorption of griseofulvin is markedly enhanced by ____.
The presence of a high fat meal
Griseofulvin is highly bound and concentrated in _____.
Keratinized cells
Griseofulvin induces ____ enzymes.
Hepatic drug metabolizing
Griseofulvin undergoes extensive _____.
Inactivation in the liver (first pass effect)
How long does griseofulvin take to reach full effect?
Several weeks - total duration of tx 1-4 months
This drug is labeled for use in horses (powder formation) for dermatophytosis.
Griseofulvin
Griseofulvin is used for treating ___ in small animals but is being replaced by ___.
Dermatophytosis
Azoles
While NOT labeled for use in food animals, this drug has been reported to be effective for treatment of dermatophytes in cattle.
griseofulvin
How is withdrawal time determined for use of griseofulvin in food animals?
DVM must determine appropriate withdrawal time
What is the MOA for flucytosine?
Pro-drug
Once inside the cytoplasm of the fungal organism, it is converted to 5-FU - an antimetabolite that interferes with Nucleic acid synthesis and metabolism, ultimately disrupting protein synthesis.
What is the spectrum of activity for flucytosine?
Cryptococcus
Some candida
Resistance to this antifungal develops commonly and quickly, so it’s often used in combination with amphotericin B.
Flucytosine
Synergism occurs with amphotericin B
Two toxicities related to flucytosine
Bone marrow suppression
Mucous membrane ulceration
Mammalian cells lack _____ and cannot convert the pro-drug 5-FC to its active form 5-FU.
Cytosine deaminase
What converts some 5-FC to 5-FU (which is toxic to mammalian cells)?
Gastrointestinal flora
What is the MOA of amphotericin B?
Fungicidal
Binds to ergosterol to form a transmembrane pore that disrupts membrane function by allowing small molecules to leak through the membrane
What is the spectrum of activity for amphotericin B?
Generally utilized only for severe systemic fungal infections such as histoplasma, blastomyces, cryptococcus, sometimes coccidiodes, and other less common fungal infections.
Dermatophytes are NOT susceptible
______ are not susceptible to amphotericin B.
Dermatophytes
Development of resistance is infrequent with this antifungal.
Amphotericin B
What kind of toxicity is common in patients treated with amphotericin B?
Nephrotoxicity
What are possible reactions related to amphotericin B toxicity?
Anaphylactic-like reactions, vomiting, and fever
_____ may reduce the occurrence or severity of nephrotoxicity with amphotericin B.
Fluid therapy
Newer and more expensive formulations of amphotericin B are ____ and greatly reduce the risk of nephrotoxicity.
Liposome encapsulated
Amphotericin B is available only for ___ use.
IV use
Diluted in 5% dextrose
Amphotericin B has a ____ plasma half life.
LONG
1-2 weeks
60% of this antifungal drug is eliminated by urine (causing nephrotoxicity).
Amphotericin B
Amphotericin B is used in small animals for treating ____.
Systemic fungal infections
blastomycosis
Histoplasmosis
Cryptococcus most commonly
What is the mechanism of action of ketoconazole?
Fungistatic
Inhibits ergosterol synthesis (ergosterol is the primary sterol of fungal cell membranes vs cholesterol in mammalian cell membranes) by inhibiting a CYP450 enzyme (CYP51A)
Do not combine amphotericin with ____.
Azoles
What is the spectrum of activity with ketoconazole?
Usually susceptible:
Candida
Malassezia
Dermatophytes
Sometimes susceptible:
Cryptosporidium immitis
Histoplasma capsulatum
Blastomyces dermatidis
____ is much safer than amphotericin B.
Ketoconazole
What are the most common signs of toxicity with ketoconazole?
GI upset and hepatotoxicity (esp. in cats)
This drug probably contributes to more serious drug interactions than any other drug in dogs.
KETOCONAZOLE
This antifungal interferes with progesterone and testosterone.
ketoconazole
Ketoconazole ____ mammalian steroid biosynthesis by inhibiting mammalian CYP enzymes
Inhibits
Ketoconazole is highly protein bound (>98%) therefore does not distribute well to __.
CNS
Prostate
Eye
Ketoconazole requires ___ for oral absorption.
Acid pH
The most common use for ketoconazole in vet med use is for ___ in dogs (topical formulations and systemic administration).
Malassezia dermatitis
Ketoconazole is used for dermatophytosis in dogs and cats and sometimes as an adjunct treatment for _____.
Systemic mycotic infections
This drug has better efficacy against Candida, Aspergillus, dermatophytes, and most systemic fungi than ketoconazole.
Itraconazole
This drug has fewer adverse effects but is more expensive than ketoconazole.
Itraconazole
Which antifungal penetrates the CNS and urinary tract?
Fluconazole
Fluconazole does not undergo ____ and is excreted via ____.
Metabolism
Urine
This antifungal has approximately 100% bioavailability in horses.
Fluconazole
Which antifungal has the best oral absorption?
Fluconazole
Oral absorption of which antifungal is independent of pH?
Fluconazole
Name two topical azole antifungal agents.
Clotrimazole
Miconazole
Is clotrimazole orally bioavailable?
No
What are three indications for use of clotrimazole?
*Topically for treating nasal aspergillosis in dogs
*Infused into bladder of dogs/cats with fungal candiduria
*Treatment of otitis externa caused by Malassezia pachydermatitis
This topical azole antifungal agent undergoes rapid metabolism and would require frequent IV infusions for systemic use.
Miconazole
Miconazole is indicated for use in treatment of ___.
Dermatophytosis in dogs and cats
What is the MOA for terbinafine?
Inhibits the enzyme squalene epoxidase which results in decreased ergosterol synthesis
How is terbinafine used?
Topically and systemically for dermatophytosis in dogs and cats
High concentrations of this antifungal agent are reached in nail beds, although it takes several months of therapy to achieve results for onychomycosis.
Terbinafine
Factors involved in therapeutic failure/relapse after antifungal tx:
Most antifungals are ______, therefore clearance of the infection relies mainly on the host response.
Fungistatics
Factors involved in therapeutic failure/relapse after antifungal tx:
_________ into the foci of infection
Poor penetration
Factors involved in therapeutic failure/relapse after antifungal tx:
Intrinsic and acquired _____ to antifungal tx
Resistance
Factors involved in therapeutic failure/relapse after antifungal tx:
_________
Toxicity
Factors involved in therapeutic failure/relapse after antifungal tx:
_________ dosage regimens
Inappropriate
Discontinuation of tx after resolution of clinical signs but not eradication of the infection
Factors involved in therapeutic failure/relapse after antifungal tx:
_____ that are not well developed
Antifungal culture and susceptibility testing methods
Four categories of antiviral agents
Neuramidase inhibitors
Assembly inhibitors
Transcription inhibitors
Interferons
Name the antiviral agent that is a neuraminidase inhibitor.
Oseltamivir
Name the antiviral agent that is an assembly inhibitor.
Amantadine
Name 7 antiviral agents that are transcription inhibitors
Idoxurine
Trifluridine
Vidarabine
Acyclovir, Famciclovir, Ganciclovir
Zidovudine (AZT)
This antiviral topical medication is used to treat viral infections of the eye, such as herpesvirus-1 in cats.
Idoxuridine
Unsubstantiated claims have been made about the efficacy of this antiviral drug for reducing the severity of parvovirus infection in dogs.
Oseltamivir
This antiviral drug has shown benefit in treating feline herpes virus in cats (ocular and respiratory manifestations).
Oral famciclovir
The FDA has banned the use of this antiviral drug in birds.
Zidovudine
This antiviral drug shows some evidence for activity against reverse transcriptase enzymes of Feline Immunodeficiency Virus and Feline Leukemia Virus, but is not curative.
Zidovudine
