Anti-Fungals Flashcards
Systemic Fungi (4)
Histoplasma
Blastomyces
Coccidioides
Sporothrix
Opportunistic (3)
Candida
Aspergillus
Cryptococcus - india ink stain
Cutaneous/Subcutaneous (2)
Sporthrix
Dermatophytes - ringworm, athletes foot, onychomycosis
Unique Targets of Fungi
Fungal cell membrane - ERGOSTEROL
Fungal cell wall - GLUCANS
Shared targets of humans and fungi
DNA/RNA Synthesis
Cell division
Systemically Active Drugs
Polyenes - AMPHO B
Azoles - most of them
FLUCYTOSINE
ECHINOCANDINS
Amphotericin B MOA
BINDS ERGOSTEROL - can also bind cholesterol (toxicity)
Forms PORES - alters membrane permeability
poor CNS penetration, but otherwise widely distributed
Amphotericin B resistance
REDUCED ERGOSTEROL LEVELS - reduces affinity for ampho B
Amphotericin B adverse reactions
infusion related - fever, chills, muscle spasms, vomiting, headache, HTN
NEPHROTOXICITY
Mechanism used to decrease ampho B toxicity?
LIPOSOMAL PACKAGED - reduces non-specific binding to human cell membranes
Azoles MOA
bind enzyme responsible for CONVERTING LANOSTEROL TO ERGOSTEROL
causes leaky, damaged cell membranes to form
Imidazoles (3)
ketoconazole
miconazole
clotrimazole
Triazoles (4)
fluconazole
itraconazole
voriconazole
posaconazole
Resistance to Azoles
EFFLUX PUMPS
target enzyme mutations
decreased ergosterol content
Ketoconazole drastically inhibits what?
CYTOCHROME P450
What azole has widest therapeutic index?
FLUCONAZOLE
90% absorption from GI tract
widely distributed
water soluble
Itraconazole vs Fluconazole
itraconazole has BROADER SPECTRUM OF ACTIVITY
POORER THERAPEUTIC INDEX
Voriconazole treatment of choice for?
Also an inhibitor of what?
ASPERGILLOSIS - decreased toxicity to ampho B
cytochrome P450
Posaconazole has what?
BROADEST SPECTRUM OF ACTIVITY
Flucytosine never used?
typically used for?
by itself
SEVERE CRYPTOCOCCAL MENINGITIS
Flucytosine adverse reaction?
BONE MARROW TOXICITY
Echinocandins MOA
3 drugs
LIPOPEPTIDES - INHIBIT SYNTHESIS OF BETA-GLUCANS (essential component of most fungal cell walls)
caspofungin
micafungin
anidulafungin
Echinocandins work well against (2)?
Candida
Aspergillus
Drugs administered orally but for skin infection?
Griseofulvin
Allylamines - terbinafine
Griseofulvin used for?
Concentrates in?
DERMATOPHYTE INFECTIONS
Keratin pre-cursor cells
Terbinafine (allylamine) MOA
First line tx for?
INHIBIT SQUALENE EPOXIDASE
ONYCHOMYCOSIS
Topical Antifungals (3)
Polyenes - nystatin
Azoles - clotrimazole, miconazole
Allylamines - terbinafine, naftifine
Nystatin most commonly used for?
local infections
oropharyngeal and vaginal candidiasis
