Block 9 Drugs- Antifungal Flashcards
Amphotericin B
MOA: binds to ergosterol found in fungal membranes and compromises the selective permeability; cells leak potassium and many low molecular weight compounds
USE: Candidiasis
Coccidioidomycosis
Cryptococcal meningitis
Aspergillosis
Mucormycosis
Blastomycosis
broadest spectrum antifungal agent
S/E: nephrotoxicity (renal tubular acidosis and renal wasting)
Supplemental K+ and/or Na+ may be given
Unique: mammalian cells contain cholesterol, rather than ergosterol; however, some binding to human membrane sterols occurs & can lead to toxicity
Non-absorbed PO; must be give IV
Ketoconazole
MOA: inhibits fungal ergosterol synthesis by inhibition of sterol 14-α-demethylase
inhibits fungal peroxidase and catalase, yielding high levels of intracellular H2O2
USE:
S/E:
CI:
Unique:
Fluconazole
MOA: inhibits fungal ergosterol synthesis by inhibition of sterol 14-α-demethylase
inhibits fungal peroxidase and catalase, yielding high levels of intracellular H2O2
USE: Compared to ketoconazole, superior against Cryptococcus neoformans, Histoplasm capsulatum, meningeal cryptococcosis and chronic pulmonary histoplasmosis
S/E: Much less toxicity compared to ketoconazole
Flucytosine
MOA: Related to 5-fluorouracil (5-FU)
Converted intracellularly first to 5-FU and then to 5-FdUMP and fluorouridine triphosphate (FUTP) which inhibit nucleic acid synthesis
Human cells unable to convert the parent drug to its active metabolites, resulting in selective toxicity
USE: Combination therapy with amphotericin B for cryptococcal meningitis
Combination therapy with itraconazole for chromoblastomycosis
S/E: Can be metabolized (possibly by intestinal flora) to 5-FU, leading to myelosuppression (anemia, leukopenia, thrombocytopenia)
Toxic enterocolitis
Griseofulvin
MOA: inhibits fungal mitosis after binding to microtubules of the mitotic spindle (mammalian microtubles are affected only at high concentrations)
USE: systemic treatment of dermatophytosis (fungal infections of skin, hair and nails)
Depositid in keratin after PO administration
S/E: Headaches
Rashes
Neutropenia
Unique: Do not use in pregnancy - teratogenic in animal models
Terbinafine (Lamisil)
MOA: Interferes with ergosterol biosynthesis - inhibits the funcal enzyme squalene epoxidase
Leads to accumulation of sterol squalene, which is toxic
USE: Fungal infections of nails
S/E: GI upset
Headache
Unique: Generally devoid of drug-drug interactions
Echinocandins (capsofugin, anidulafungin, micafungin)
MOA: Inhibit the formation of 1,3-D-glucans in fungal cell wall
Inhibition of glucan synthesis reduces cell wall structural integrity → osmotic instability and cell death
USE: Candida spp.
Aspergillus spp.
S/E: Minor GI upset
Flushing
Unique: Must be adminstered IV
