Antifungals Flashcards
Who are the triazoles?
Fluconazole
Voriconazole
Itraconazole
Posaconazole
Who are the polyenes?
amphoteracin B
Nystatin (topical)
Who are the echinocandins?
capsofungin, micafungin and anidulafungin
who is the pyrimidine analog?
Flucytosine
Azoles MOA
IMPEDE ERGOSTEROL SYNTHESIS by inhiiting lanosterol demethylase (14-alpha sterol demethylase)
—**not CIDAL the host has to wipe them out all the way. It stpops fungal growth
Fluconazole spectrum of activity is broad or narrow?
narrow spectrum
- It targets Candida spp.–yeast infections (Candidiasis, severe thrush, esophageal candidiasis
- Cryptococcus (2nd line Tx ) and
**not for molds or hard to treat but is safe
Do Voriconazole, Itraconazole have a greater or a lesser spectrum of activity than Fluconazole?
both have wider spectrum of activity and better for molds-
It treats everything below and broader Candida coverage
ITRACONAZOLE for *Histoplasmosis - long term after Amphotericin B
*high mortality risk
Which Azole has the broadest spectrum?
Posconazole
It covers everything below and Fusarium, MUCORales, Aspergillus
What are the adverse effects of Azoles?
- Liver enzyme abnormalitites - monitor LFT for no liver toxicity * Fluconazole has the least effect
- GI
Which Azole will you get visual disturbances (bluish hue) from?
Voriconazole
Drug interactions
All inhibit CYP450 in fungal and mammalian (Fluconazole the least drug interactions
What is Voriconazole used to Tx?
invasive ASPERGILLUS
Posiconazole is used mostly as
prophylactic
If an HIV patient is on Itraconazole, Diltiazem (for BP) and some HIV meds (Ritonavir), what drug interactions are you concerned about?
Itraconazole inhibits metabolism of dilitazem. Closer monitoring of BP and perhaps lowering of diltiazem dose is needed.
–Ritonavir inhibits the metabolism of Itraconazole substantially so you have to give high doses of Itraconazole
Which drug is considered the grandfather of antifungals? And what is its MOA
Amphotericin B - inhibits ergosterol (already synthesized by generating pores in the fungal wall
What is the spectrum of Amphotericin B?
very broad - Candida, Aspergillus, Zygomyces, Histoplasma, Cryptococcus
What are the side effects of Amphotericin B
- NEPHROTOXICITY - elevated serum creatinine
- acute infusion related reactions - fever, chills, rigors <– pre-medicate with diphenhydramine (Benadryl), APAP, Meperidine
- Electrolyte abnormalities - low Mg+, low K+
What is the solution to Amphotericin’s awful side effects?
Lipid formulations (Abelcet, Liposomal Amphotericine B- L-AMB)- they have better tolerability and renal protective and you can increase the dose safely *Expensive
The newest class: Echinocandins (capsofungin) are “me too drugs” approved for
Candida infections- resistant to azoles
Refractory ASPERGILLUS infection
Esophageal candidiasis
Febrile neutopenic patients prophylaxis
Are the echinocandins avalialbe IV or PO
IV only
How safe are Echinocandins?
very safe - it is hepatically cleared so you adjust if liver dysfunction
- -very few drug interactions
- -Excellent for Candida and MOLDS
Which pyrimidine analog inhibits DNA and RNA synthesis in fungi and molds?
Flucytosine
What is the spectrum of activity of Flucytosine?
Narrow and is active against *Cryptococcus and some Candida spp.
Which other antifungal does Flucytosine exhibit synergy with??
Amphotericin B
- combo used especially for Cryptococcal Meningitis
- Don’t use Flucytosine alone - resistance quickly develops
Which antibiotic is a prodrug?
Flucytosine (comes from 5-FU in fungus)
side effects of Flucytosine
bone marrow toxicity
liver dysfunction
N/V
