Antifungals Flashcards
2 groups of fungal infections
Systemic
Superficial
What do fungi use to maintain plasma membrane structure/function?
Ergosterol
How is ergosterol made by fungi?
Squalene —> lanosterol —> ergosterol
Fungal cell wall components
Chitin
B-D-glucans
Glycoproteins
Inhibitor of fungal membrane stability
Amphotericin B
Amphotericin B MOA
Binds ergosterol and forms pores in the membrane
Clinical uses of Amphotericin B
Broad spectrum, LIFE-THREATENING systemic fungal infections
(Boxed warning for appropriate.use only)
How should Amphotericin B be administered
IV infusion over 4-6 hours (cytokine storm if not given slowly)
Amphotericin B adverse effects
Renal toxicity
Myelosuppression resulting in anemia (less EPO released from kidneys)
Fungal nucleic acid synthesis inhibitor
Flucytosine
Flucytosine MOA
Inhibits DNA/RNA synthesis
is converted to 5-FU then 5-FdUMP which inhibits thymidylate synthase
Clinical uses of flucytosine
Narrow spectrum used for cryptococcal meningitis and systemic candidiasis
Used in combination with Amphotericin B
Boxed warning for flucytosine
Dose reduction in patients with renal insufficiency
Adverse reactions of flucytosine
Direct myelosuppression (monitor CBC)
Hepatotoxicity
Fungal mitotic inhibitor
Griseofulvin
Griseofulvin MOA
Binds tubulin to disrupt assembly of mitotic spindle
Griseofulvin accumulates in ____ precursor cells to allow new growth of skin, hair, and nails to be free of fungal infection
Keratin
Griseofulvin is not effective against ___ or ____
Candida
Systemic fungal infections
Clinical uses of griseofulvin
Oral administration to treat dermatophyte infections of hair, skin and nails, including scalp ringworm
How long does griseofulvin take to work?
Up to 6 months
Griseofulvin adverse effects
Headaches
Photosensitivity
Fungal squalene epoxidase inhibitor
Terbinafine
Terbinafine MOA
Prevents conversion of squalene to lanosterol by inhibiting squalene epoxidase
Causes toxic accumulation of squalene
Clinical uses of Terbinafine
Topical use for ringworm/tinea
Oral use for onychomycosis
Adverse effects of Terbinafine
Dermal irritation
Taste disturbance (dysgeusia)
Hepatotoxicity
Fluconazole MOA
Blocks conversion of lanosterol to ergosterol by inhibiting 14a-sterol demethylase
Fluconazole clinical uses
Broad spectrum
Cryptococcal meningitis
Superficial mycoses
Candida yeast infections
Fluconazole adverse effects
GI upset
Inhibits CYP (drug interactions)
Hepatotoxicity
When is fluconazole contraindicated?
Pregnancy
Inhibitor of fungal cell wall synthesis
Caspofungin
Caspofungin MOA
Disrupts cross-linking of cell wall causing osmotic stress and cell lysis (fungicidal)
Clinical uses of caspofungin
Severe systemic candida infections
Empiric therapy for persistent febrile neutropenia
