Antifungal chemotherapy Flashcards
what are the opportunistic fungal infections?
candida
aspergillus
cryptococcus
onychomycosis causes what type of fungal infection?
cutaneous / subcutaneous
dimorphic fungi usually cause what type of infection?
systemic
what are the unique targets for fungi?
fungal cell membrane (ergosterol, ergosterol synthesis)
fungal cell wall (glucans)
what is the MOA of amphotericin B?
weaken membrane function (bind ergosterol)
forms amp B containing pores to alter membrane permeability
caspofungin targets what fungal component / process?
cell wall synthesis
5-flurocytosine targets what fungal component / process?
nucleic acid synthesis
what are the systemically active drugs used for systemic infections?
polyenes
azoles
flucytosine
echinocandins
what is the most widely used drug in treating systemic mycoses?
amphotericin B
what drug has the broadest spectrum of action and is useful against systemic fungal infections?
amphotericin B
when does amphotericin B resistance occur?
decrease in membrane ergosterol concentration
modification of target - reduced affinity
what is the tissue penetration profile of amphotericin B?
widely distributed into most tissues but poor CNS penetration
what is the most common and most serious long term toxicity associated with amphotericin B?
nephrotoxicity
what is done to make amphotericin B less toxic? why?
liposomal packaged formulations
less interaction of drug with mammalian cell membrane
what is the MOA of the azoles?
inhibit ergosterol synthesis - bind to enzyme responsible for converting lanosterol to ergosterol
causes leaky membranes
what are the clinical uses for the azoles?
pathogenic yeast
systemic mycoses
dermatophytes
what are the adverse reactions of the azoles?
minor GI disturbances
interaction with hepatic cyp450s
what are the MORs of the azole drugs?
efflux pumps
mutations in target enzyme
decreased ergosterol content in cell membrane
which azole has the highest therapeutic index of all the azoles?
fluconazole
fluconazole is the agent of choice for what conditions?
candidiasis
cryptococcosis
coccidiomycosis
what is the drug of choice for candidiasis, cryptococcosis, and coccidiomycosis?
fluconazole
what is the drug of choice for blastomycosis, coccidiomycosis, histoplasmosis, sporotrichosis, and dermatophyte?
itraconazole
itraconozole is the drug of choice for what conditions?
blastomycosis coccidiomycosis histoplasmosis sporotrichosis dermatophyte
what drug has replaced amphotericin B as treatment of choice for aspergillosis?
voriconazole
what is the drug of choice for aspergillosis?
voriconazole
what azole has the highest spectrum of activity?
posaconazole
what are the main indications for posaconazole?
aspergillus
agents of mucormycoses
flucytosine is used as part of combination therapy for what organisms?
cryptococcus
candida
what is the MOA of flucytosine?
interferes with both protein and nucleic acid synthesis
flucytosine is effective against which organisms?
cryptococcal infections
what test is used to identify cryptococcus neoformans?
india ink stain
the india ink stain is used to identify which organism?
cryptococcus neoformans
which drug is effective against cryptococcus neoformans and meningitis?
flucytosine
what is the main toxicity of flucytosine?
bone marrow suppression
what is the general MOA of the echinocandins? what dictates their selectivity?
inhibit fungal cell wall synthesis
attack beta glucans (not present in mammalian cells)
what are the main indications for the echinocandins?
candida and aspergillus
what are the oral systemic drugs for cutaneous and mucocutaneous infections?
griseofulvin
allylamines (terbinafine)
griseofulvin and allylamines (terbinafine) are used for what purposes, generally?
cutaneous and mucocutaneous infections
what drug is used orally for dermatophyte infections?
griseofulvin
what specific infection is griseofulvin used for?
dermatophyte
what is the MOA of the allylamines?
ergosterol synthesis inhibitors
what is the first line treatment for onychomycosis?
terbinafine (allylamine)
terbinafine is the first line treatment for what condition?
onychomycosis
what are the topical antifungal classes?
polyenes
azoles
allylamines
nystatin is useful against what type of infection?
candida
