Antifungals Flashcards
Amphotericin B
Polyein
Binds ergosterol in cell membrane of fungi -> pores in membrane
-> Loss of electrolytes and small molecules
-> fungal cell death
Can bind cholesterol in human cells -> SE “Amphiterrible” fever, chills hypotension hypokalemia anemia phlebitis arrhythmias NEPHROTOXICITY!!! -minimized by proper hydration prior to administration -use lipid formulations
Uses: systemic fungal dz if severe or first line drug failing Cryptococcosis Blastomycosis Coccidioidomycosis Aspergillosis Histoplasmosis Mucormycosis
IV dosing – infusing intrathecally to avoid BBB
Nystatin
Polyein
Binds egosterol of fungi cell membrane forming pores
Topical use only
Uses:
cutaneous candidiasis – diaper rash, vulvovaginalis
Oropharyngeal candidiasis – swish and swallow, not absorbed well in GI
-azoles
Clotrimazole Fluconazole Itraconazole Ketoconazole Miconazole Posaconazole Voriconazole
Inhibit synthesis of ergosterol
Inhibits P450 enzyme that converts lanosterol to ergosterol
Use:
Topically for cutaneous infections
Orally/IV for systemic
Toxicity:
Decrease production of cortisol and T -> gynecomastia, impotence
Drug-drug interaction via CYP 450
Elevate hepatic enzymes
Use of voriconazole
Aspergillus
Use of posaconazole
Refractory fungi – esp mucor
Use of clotrimazole and miconazole
Topical fungal infections
Use of Fluconazole
Cryptococcal meningitis
Candida infections
Use of Ketoconazole
Blastomyces
Coccidiodes
Histoplasma
Candida
Use of Itraconazole
1st line for dimorphic fungi Blastomyces Coccidioides Paracoccidioides Histoplasma Sporothrix
Draw out anti fungal diagram
Page 376
Flucytosine
Converted to 4-fluorouracil
Disrupts DNA and RNA synthesis – false nt
Used w/ amphotericine B
- systemic candida infections
- cryptococcal infections
Toxicity: bone marrow toxicity
GI sx: N/V/D
Echinocandin
Caspofungin
Mycofungin
Inhibit cell wall synthesis via inhibition of b-(1,3) – D-glucan synthesis
Use: invasive aspergillosis
Candida infections
Tox: GI upset, flushing
Terbinafine (Lamisil)
Inhibits fungal enzyme squalene epoxidase decreasing ergosterol synthesis
Topically: tinea pedis, tinea corporis
Oral: onychomycosis, tinea capitis
Tox: GI sx, hepatotoxicity
Griseofulvin
Targets microtubule function, inhibits mitosis
Deposits in keratin-containing tissues
Clinical uses: tinea corporis, tinea capitis, onychomycosis
Tx: 6-12 mo
AE: Teratogenicity HA GI sx Confusion CYP450 inducer
