MOA of Amphotericin B?
Complexes with ergosterol to disrupt fungal cell membrane
Which 3 major classes of fungi can be treated with Amphotericin B and list the 7 organisms in these classes?
- Yeasts: Candida + Cryptococcus neoformans
- Organisms causing endemic mycoses: H. capsulatum + Blastomyces dermatitidis + Coccidioides immitis
- Pathogenic molds: Aspergillus fumigatus + agents of mucormycosis
What is the mechanism of resistance to Amphotericin B?
Alteration to ergosterol
What is the route of administration for Amphotericin B?
What are the most common immediate and long term AE's associated with Amphotericin B?
- Immediate = FEVER, chills, muscle spasms, vomiting, HA, and hypotension
- Long term = renal toxicity
What is the MOA of Flucytosine?
Converted to FdUMP and FUTP, which inhibit DNA and RNA synthesis, respectively
Which 2 organisms can be treated with Flucytosine?
- C. neoformans
- Some Candida spp.
What is the mechanism of resistance to Flucytosine?
Altered drug metabolism
How is Flucytosine administered?
Water-soluble oral form
What are 3 AE's of Flucytosine?
What is the MOA of the Azoles?
Inhibition of fungal CYP450 enzymes --> ↓ ergosterol synthesis
What is the mechanism of resistance to the Azoles?
Upregulation of fungal CYP450 enzymes
What are 2 AE's associated with the -azoles?
- Minor GI issues***
- Abnormalities in liver enzymes
Which -azole has a greater propensity to inhibit mammalian CYP450 enzymes?
Which -azole used for fungal infections has poor CSF penetration and which has good CSF penetration?
- Poor penetration = Itraconazole
- Good penetration = Fluconazole
Which routes of administration exist for Itraconazole?
Oral and IV
List 6 fungi which can be treated with Itraconazole?
- Dimorphic fungi: Histoplasma, Blastomyces, and Sporothrix
- Aspergillus spp. (largely replaced by voriconazole)
- Dermatophytoses and onychomycosis
In which form does Fluconazole have the highest bioavailability and via which routes can it be given?
- High oral bioavailability
- Can be given via IV as well
Which 3 -azoles have the highest absorption and are more often used for systemic coverage?
What is the azole of choice for cryptococcal meningitis?
Fluconazole is most commonly used for the treatment of what?
Via which routes can Voriconazole be given?
IV and oral
Voriconazole is an inhibitor of what?
Which 3 -azoles have both oral and IV formulations?
What is a common AE of Voriconazole?
Voriconazole has a similar spectrum to what other -azole?
What is the treatment of choice for invasive aspergillosis and some enviornmental molds?
Which -azole can be given for Candida infections, including fluconazole-resistant specices such as Candida krusei and the dimorphic fungi?
How is Posaconazole administered?
Liquid oral preparation only
What is the only -azole with significant activity against the agents of mucormycosis?