51 Pharm Antivirals + Antifungals Flashcards
What is the difference between fungistatic and fungicidal?
Fungistatic - inhibits growth
Fungicidal - kills
What is an important principle regarding duration of fungal treatment?
Treatment must be of sufficient duration because many drugs are fungistatic and fungi grow slowly
Why does antifungal treatment often cause signs to worsten before they get better?
Inflammation
What part of fungi do antifungals usually target?
Cell membrane or cell wall
What kind of case would you prescribe Amphotericin B for?
Severe systemic fungal infections
Amphotericin B is (fungistatic/fungicidal).
Fungicidal
What is the MOA of amphotericin B?
Binds ergosterol, causes rapid K+ efflux (and other cations), inhibits fungal glycolysis, causes oxidative damage
T or F: amphotericin B can be administered orally or IV.
F; poor oral bioavailability so IV
What kind of toxicity should you worry about when using Amphotericin B?
Nephrotoxicity (dose dependent)
(Imidazoles/triazoles) have a greater effect on mammalian cholesterol synthesis.
Imidazoles
What is the MOA of azole antifungals?
Inhibits ergosterol synthesis causing accumulation of toxic methylated sterols in the plasma membrane; alters membrane fluidity and barrier function.
Azole antifungals are (fungistatic/fungicidal).
Fungistatic
What negative effects can azoles have on the patient?
Inhibition of mammalian CYP450; hepatotoxicity
When in the day should ketoconazole be administered and why?
After a meal because it is only soluble in acidic environments
What are the clinical indications for ketoconazole?
Superficial yeast infections, dimorphic fungi, or dermatophytosis
What are some toxic/adverse effects of ketoconazole?
-Nausea, anorexia, vomiting
-Increase in hepatic enzymes not associated w/ injury
-Hepatic disease or failure
-Inhibition of mammalian CYP450
-Inhibits cortisol and testosterone synthesis
T or F: fluconazole is effective against yeast, molds, and dimorphic fungi.
F; not effective againt molds
How is ketoconazole eliminated?
Hepatic metabolism
How is fluconazole eliminated?
Renal excretion
What is itraconazole effective against?
All significant fungi including molds
What kind of toxicity can fluconazole cause?
Rare hepatic toxicity
What are potential adverse effects of itraconazole?
Vomiting (esp cats), hepatotoxicity, cutaneous vasculitis
What is voriconazole effective against?
Molds
What drug is analagous to itraconazole?
Posaconazole
T or F: flucytosine is toxic to cats.
F; toxic to dogs
What is flucytosine effective against?
Candida and cryptococcus
What adverse effects can flucytosine have?
Bone marrow suppression, nausea, vomiting, diarrhea, cutaneous eruptions in dogs
What is griseofulvin used to treat?
Dermatophytosis
What is the MOA of griseofulvin?
Binds microtubules of mitotic spindle to inhibit fungal mitosis
What are some toxic effects of griseofulvin?
Idiosyncratic toxicity in cats; teratogenic during early gestation in mares
What are common topical antifungals?
Clotrimazole (otomax), enilconazole, miconazole
What would you use caspofungin for?
Treat systemic aspergillosis or candidiasis
What is the MOA of caspofungin?
Inhibition of glucan synthesis; disruption of cell wall
Why is it difficult to make selective antiviral agents?
Viruses are obligate intracellular parasites that use host cell machinery, have variable life cycles, and can become resistant. Plus screening is tested in vitro and not all viruses will grow in vitro
What are acyclovir and valacyclovir used to treat?
Herpesvirus
What is the MOA of acyclovir and valacyclovir?
Targets replication by inhibiting DNA polymerase
What domestic species is valacyclovir toxic to?
Cats
What is the MOA of penciclovir and famciclovir?
Inhibits DNA polymerase and is a substitute for guanosine
What are idoxuridine/trifluridine used to treat?
FHV-1
What is the MOA of idoxuridine/trifluridine?
Interrupts DNA polymerase; substitute for thymidine
How is idoxurine administered and why?
Topical and ophthalmic because it can cause toxic neoplastic changes, genetic mutations, or infertility
