Antifungals Flashcards
Amphotericin B: Mechanism of Action
Binds selectively to ergosterol (structurally related to cholesterol) to disrupt the fungal cell membrane function (fungicidal)
Amphotericin B: Therapeutic Uses
- Used for most systemic fungal infections
- Also used to treat leishmaniasis (protozoan)
Amphotericin B: Spectrum
Broad spectrum of antifungal activity
How is Amphotericin B given?
Not absorbed orally; MUST be given IV
Amphotericin B: Adverse Effects
- Nephrotoxicity
- Lipid formulations have reduced renal toxicity
Echinocandins (Caspofungin): Mechanism of Action
Inhibits synthesis of cell wall polysaccharides
Caspofungin: Therapeutic Uses
- Alternate therapy for serious systemic fungal infections
How is Caspofungin given?
Poor oral absorption; given IV
Flucytosine: Mechanism of Action
Blocks DNA synthesis by inhibiting thymidylate synthetase
Flucytosine is a prodrug. What enzyme activates this drug?
Selectively activated to 5-fluorouracil by fungal-specific enzyme called cytosine deaminase
Flucytosine: Therapeutic Uses
- Synergistic in combination with Amphotericin B (because the Amphotericin B disrupts the membrane, the Flucytosine will go into the cell easier)
Flucytosine: Adverse Effects
- Enterocolitis
- High prolonged serum levels may cause bone marrow suppression
Itraconazole: Mechanism of Action
Inhibits cytochrome P-450 mediated synthesis of ergosterol by fungi
Itraconazole: Spectrum
Extended to Broad Spectrum
Itraconazole: Drug Interactions
- Can increase the plasma level of other drugs (e.g. phenytoin, cyclosporin)
Nystatin: Mechanism of Action
Same mechanism as Amphotericin B
- Binds selectively to ergosterol (structurally related to cholesterol) to disrupt the fungal cell membrane function (fungicidal)
Nystatin: Therapeutic Uses
Only useful for the treatment of Candidiasis
How is Nystatin given? Why doesn’t it cause toxicity?
Orally; because it doesn’t get absorbed well it will get expelled and limits systemic toxicity
Miconazole: Mechanism of Action
Same as Itraconazole
-Inhibits cytochrome P-450 mediated synthesis of ergosterol by fungi
Miconazole: Therapeutic Uses
Used to treat superficial infections (orally and topically)
How is Miconazole given?
Orally for the same reason as Nystatin
Terbinafine: Mechanism of Action
Inhibits ergosterol synthesis by a different mechanism than Miconazole and Itraconazole
Terbinafine: Therapeutic Uses
- Taken orally for the treatment of severe or extensive superficial infections (concentrates in skin and nails)
- Can also be used topically
What drugs are used to treat superficial fungal infections?
Nystatin, Miconazole, Terbinafine
