Antifungal Chemotherapy Flashcards
Unique aspects of fungal cells and fungal metabolism, which provide targets for chemotherapy and account for selective toxicity.
Fungal cell membranes
- membrane: ergosterol and ergosterol synthesis
- Synthesis: Azoles, Terbinafine
- Ergosterol: Amphoteracin B, Nystatin
Fungal cell wall
- Glucans
- Echinocandins - weaken wall
Flucytosine targets DNA, RNA - shared target
MOA
Azoles
all have -azole suffix
Inhibit Ergosterol Synthesis, results in leaky membrane
Resistance is increasing (efflux pump, mutation in target enzyme, decreased ergosterol in cell membrane)
Adverse Rxn: minor GI, interaction with CYP450 enzymes
Topical Azoles in many OTC: Clotrimazole and Miconazole - tx Vulvovaginal candida, dermatophytes
Oral lozenges for oral thrush - resistance is rare
MOA
Echinocandins
Newest class of antifungals
Inhibit synthesis of Beta-Glucans - fugal cell wall
3: Caspofungin, Micafungin, Anidulafungin
Humans dont have Beta glucans
usefulness limited to fungi with high levels of B glucan
Primarily for invasive infections: Candida, Aspergillus
Very expensive so used as last resort
wide distribution - NOT TO CNS
Adverse Rxn: Extremely well tolerated, some drug interactions have been reported
MOA
Allylamines
Inhibitors of Ergosterol Synthesis - cell membranes
Drug: Terbinafine
Topical allylamines in OTC: Terbinafine, Naftifine for tinea cruris, tinea corporis
Recommendations for treating aspergillosis
Voriconazole - #1
Posaconazole - broadest spectrum azole also works
Recommendations for treating blastomycosis
Itraconazole - #1
Fluconazole -#2
Amphoteracin B followed by Itraconazole for Severe
Recommendations for treating candidiasis
Esophageal - Fluconazole - #1
Vaginal - Clotrimazole, Miconazole, IV Nystatin, Fluconazole
Oropharyngeal: Clotrimazole, Miconazole, Nystatin Rinse, Fluconazole
Invasive inf in blood: Echinocandin or Fluconazole
Recommendations for treating cocciciodomycosis
Fluconazole or Itraconazole - #1
Amphoteracin B #2
Recommendations for treating cryptococcocosis
Fluconazole - #1
Flucytosine + Amp B followed w/Fluconazole- For Cryptococcal Meningitis
Recommendations for treating histoplasmosis
Amphoteracin B followed by Itraconazole - #1
Fluconazole - #2
Recommendations for treating mucormycosis
Amphoteracin B - #1
Posaconazole - #2
Recommendations for treating sporotrichosis
Cutaneous - Itraconazole - #1
Extracutaneous - Amphoteracin B followed w/Itraconazole
Major therapeutic indications for drugs used in tx:
Mucocutaneous fungal infections
Nystatin - oral/vaginal candida
Clotrimazole and Miconazole - vulvovaginal candida
Major therapeutic indications for drugs used in tx:
Cutaneous fungal infections
Clotrimazole, Miconazole or
topical terbinafine
Griseofulvin
Dermatophyte Infections
Very insoluble, absorbed as a microcrystalline form, better with fatty meal
BINDS to KERATIN - prolonged resistance to fungal inv
Interferes with Microtubule function?
Tx until infection resolved and damaged tissue replaced
Largely replaced by newer Azoles and Allylamines, NOW is second line
DRUG int: Inc Warfarin metabolism, Dec efficacy of Oral Contraceptives
