Anti-fungals Flashcards
Which drugs inhibit ergosterol synthesis?
azoles, terbinafine
Which drugs treat onychomycosis?
fluconazole, itraconazole, terbinafine
Which drugs inhibit cyt P450?
azoles, esp ketoconazole
Which drugs cause liver dysfunction?
azoles, griseofulvin
Describe the formation of ergosterol for fungal membranes.
Squalene–>lanosterol via squalene epoxidase
lanosterol–>ergosterol
Describe the formation of nucleic acids in fungus.
precursors–>pyrmidines–>nucleic acid
What is the basic MOA of the following anti-fungals? azoles terbinafine flucytosine griseofulvin amphotericin B nystatin
azoles–>inhibit lanosterol–>ergosterol
terbinafine–>inhibits squalene epoxidase
flucytosine–>inhibits DNA/RNA synthesis after becoming 5-FU
griseofulvin–>inhibits microtubule formation
amphotericin B–>forms holes in ergosterol membrane
nystatin–>forms holes in ergosterol membrane
What are the important things to know about amphotericin B?
binds ergosterol and forms holes in membrane
allows leakage of electrolytes
good for systemic mycosis, like cryptococcus meningitis
SE: nephrotoxicity! fever/chills hypotension, hypokalemia arrhythmias phlebitis
How can you help decrease the nephrotoxicity while taking amphotericin B?
hydrating
taking w/ lipophilic version of amphotericin
What are the important things to know about nystatin?
forms holes in ergosterol membrane
VERY potent, so only approved for use topically
used for oral candida, vulvovaginitis, diaper rash
What are the important things to know about flucytosine?
flucytosine–>5-FU via cytosine deaminase
5-FU inhibits RNA/DNA synthesis
used w/ amphotericin B for cryptococcal meningitis
can cause bone marrow suppression
What do you need to know about the azoles?
inhibits synthesis of ergosterol
inhibit CYTp450–>can cause liver dysfunction and elevated liver enzymes
can mess w/ hormones–>ketoconazole: gynecomastia
What are the topical azoles?
clotrimazole
miconazole
What are the typical indications for fluconazole?
cryptococcal meningitis, candida
What are the usual indications for itraconazole?
blastomyces, coccidioides, histoplasma (dimorphic)
Which of the azoles can be used to treat aspergillus?
voriconazole
Which one of the azoles can be used for refractory fungi?
posaconazole
What are the important things to know about terbinafine?
inhibits squalene epoxidase, decreases ergosterol synthesis
dermatophytoses
What is good to know about echinocandins?
inhibits cell wall synthesis by inhibiting formation of beta glucan
- *caspofungin, anidulafungin, micafungin
- *can cause GI, flushing
What are the indications for caspofungin?
C-candida, ASP-aspergillosis Fungin
What’s the deal with griseofulvin?
interferes w/ microtubule formation
disrupts mitosis
goes to keratin-containing tissues, so it is good for skin infections and tinea
What are the side effects of griseofulvin?
teratogenic carcinogenic confusion HA increases Cytp450 and can increase warfarin metabolism
