Antfungals Flashcards
Name the Triazole antifungals…
Fluconazole
Itraconazole
Posaconazole
Voriconazole
What is the mechanism of action of the -azoles?
Impeded ergosterol synthesis through direct inhibition of the cytochrome P450 dependent enzyme 14-alpha-sterol-demethylase
–> enzyme necessary for the biosynthetic pathway of ergosterol, which is an essential molecule of the fungal cell membrane
Inhibition of lanosterol demethylase
What are the major uses of fluconazole?
Some Candida spp
Cryptococcus
Endemic mycoses
What are the major uses of Voriconazole and itraconazole?
Everything covered by fluconazole and aspergillus and broader Candida app. coverage
What are the major uses of Posaconazole?
Everything covered by fluconazole, Voriconazole, and itraconazole and
- Fusarium
- Mucorales
What are the major side effects seen with the -azoles?
Hepatotoxicity
Inhibits CYP450
What is the side effect seen with Voriconazole?
Visual disturbances–Bluish hue
Used for thrush/esophageal candidiasis?
Fluconazole
Used for prophylaxis of systemic histoplasmosis?
Itrazonazole
Used for invasive aspergillosis?
Voriconazole
Used for prophylaxis of aspergillosis/candidiasis in immunocompromised pts?
Posaconazole
What is the mechanism of action of amphotericin B?
Inhibition of ergosterol–generates pores in the fungal cell membrane–allowing leakage of K and Mg
What are the major uses of amphotericin B?
Life-threatening invasive fungal infections
Broad anti fungal spectrum
Occasionally used with flu cytosine in immunocompromised hosts
What are the side effects seen with amphotericin B?
Nephrotoxicity!! –Pretty much expected with chronic use
Acute infusion related reactions
- Fever, chills, rigors
- Pre-medicating with diphenhydramine, APAP, meperidine
Electrolyte abnormalities
- HypoMg
- HypoK
What is used for better tolerability of amphotericin B?
Lipid formulations
Name the Echinocandins…
Caspofungin
Micafungin
Anidulafungin
What is the mechanism of action of the echinocandins?
Inhibit synthesis of Beta (1,3)-D-glucan–an essential component of the fungal cell wall
What are the uses for the echinocandins?
Life-threatening fungal infections unresponsive to older agents
- Candida
- Aspergillus
What is the mechanism of action of Flucytosine?
Pyrimidine analogue that inhibits DNA and RNA synthesis
What are the uses for flucytosine?
Used in combo with amphotericin B in life threatening fungal infections in immunocompromised pts
- Cryptococcus
- Some Candida spp
Develops resistance quickly if used as mono therapy
What are the side effects of Flucytosine?
Bone marrow toxicity
- Leukopenia
- Anemia
- Thrombocytopenia
Liver dysfunction possible
What is the mechanism of action of nystatin?
Pores are formed in the fungal cell membrane–allowing leakage of K and Mg
What are the uses of nystatin?
Topically against superficial fungal infections–candidiasis only
What is the mechanism of action of efinazonazole?
Inhibit ergosterol synthesis by inhibiting lanosterol demethylase
