Antifungal Flashcards
Unique targets for anti fungal therapy
Fungal cell membrane
Fungal cell wall
What drugs can be used for systemic fungal infections?
Amphotericin B, most azoles, fucystosine, and echinocandins
Amphotericin B MOA
Binds to egosterol in fungal cell membrane, and forms amp B containing pores=>alter membrane permeability=>fungicidal
Amphotericin B recommended use
Systemic Candidiasis
Cryptococcal Meningitis
Systemic disease caused by molds, including dimorphics
Amp B resistance
Reduced concentration of erogsterol in the membrane
Amp B Pharm properties
Nearly insoluble in water, widely distributed except for CNS
Amp B Adverse
Infusion reaction in almost all patients=> fever, chills, muscle spasms, vomiting, headache, HTN
Nephortoxicity=>decreased renal perfusion
Azoles MOA
Inhibit enzyme responsible for ergosterol synthesis=>make membrane leaky and damaged
Azole spectrum of activity
Pathogenic yeast=>candida and cryptococcus
Systemic mycoses
Dermatophytes
Azole resistance
Efflux pumps, mutation in target genes, and decreased ergosterol content in membrane
Azoles Adverse
Relatively non-toxic
Some GI problems
Interaction with P450=>varies from drug to drug
Fluconazole distinguishing characteristics, first line treatment for?
First line drug for many fungal infections=>highest therapeutic index
Widely distributed including CNS
Lowest interaction w/ P450 enzymes
Agent of choice for: candida, cryptococcis, coccidiomycosis
Itraconazole compared to fluconazole
Lipophilic
Broader spectrum of activity
Lower therapeutic index
More drug-drug interactions
Voriconazole Spectrum of activity. What is voriconazole the tx of choice for?
Very broad=> candida, endemic dimorphics
**due to low toxicity, has replaced amp B as tx of choice for aspergillosis
Voriconazole adverse rxns
Transient visual disturbances and hallucinations
Posaconazole spectrum of activity
Broadest spectrum of all azoles
Effective in treating Candida, Aspergillus, and agents of mucormycoses in diabetic patients
Flucytosine MOA
Interferes w/ both protein and nucleic acid synthesis
Flucytosine use
Combo therapy to treat severe cryptococcal infections (India ink stain!)
Flucytosine adverse reactions
Bone marrow toxicity=>anemia, leukopenia, thrombocytopenia
Echinocandins MOA
Inhibit synthesis of B-glucans=>weaken the cell walls of fungal cells.
3 Echinocandin drugs
End in fungin
Capsofungin
Micafungin
Anidulafungin
Echinocandins use
Treat invasive disease caused by Candida and Aspergillus=>used when fungal disease does not respond to toher drugs
Echinocandins pharmacology
Need to be IV, poor penetration to CNS
Echinocandins Adverse
Extremely well tolerated=>only attack compounds that exist in fungal cell walls
Oral drugs used for cutaneous/mucocutaneous infectiosn
Griseofulvin
Terbinafineq
Griseofulvin Use/Target cells
Dermatophyte infections
Targets kerating precursor cells
Terbinafine MOA
Inhibits enzye squalene epoxidase
Terbinafine Use
First line tx for onychomycosis
Keratophilic=>concentrates in skin, hair, and nails.
Terbinafine adverse
Rare=> GI distress, headache, elevated liver enzymes (does NOT interact w/ p450 system)
Topical antifungal agents
Nystatin
Clotrimazole, miconazole
Terbinafine, Naftifine
Nystatin MOA
polyene, binds to ergosterol in fungal cell membrane
Nystatin Use
Only topically, used to treat local infections
Also used to treat thrush (candida in the mouth)
Clotrimazole and miconazole Use
Vulvovaginal candidiasis and dermatophytes=> athlete’s foot, jock itch, ringworm, etc.
Oral lozenges available for tx of thrush
Terbinafine and Naftifine use
jock itch and ringworm
