Antifungals

Question 1

Who are the triazoles?

Answer 1

Fluconazole
Voriconazole
Itraconazole
Posaconazole

Question 2

Who are the polyenes?

Answer 2

amphoteracin B

Nystatin (topical)

Question 3

Who are the echinocandins?

Answer 3

capsofungin, micafungin and anidulafungin

Question 4

who is the pyrimidine analog?

Answer 4

Flucytosine

Question 5

Azoles MOA

Answer 5

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

Question 6

Fluconazole spectrum of activity is broad or narrow?

Answer 6

narrow spectrum

1. It targets Candida spp.–yeast infections (Candidiasis, severe thrush, esophageal candidiasis
2. Cryptococcus (2nd line Tx ) and

**not for molds or hard to treat but is safe

Question 7

Do Voriconazole, Itraconazole have a greater or a lesser spectrum of activity than Fluconazole?

Answer 7

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

Question 8

Which Azole has the broadest spectrum?

Answer 8

Posconazole

It covers everything below and Fusarium, MUCORales, Aspergillus

Question 9

What are the adverse effects of Azoles?

Answer 9

• Liver enzyme abnormalitites - monitor LFT for no liver toxicity * Fluconazole has the least effect
• GI

Question 10

Which Azole will you get visual disturbances (bluish hue) from?

Answer 10

Voriconazole

Question 11

Drug interactions

Answer 11

All inhibit CYP450 in fungal and mammalian (Fluconazole the least drug interactions

Question 12

What is Voriconazole used to Tx?

Answer 12

invasive ASPERGILLUS

Question 13

Posiconazole is used mostly as

Answer 13

prophylactic

Question 14

If an HIV patient is on Itraconazole, Diltiazem (for BP) and some HIV meds (Ritonavir), what drug interactions are you concerned about?

Answer 14

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

Question 15

Which drug is considered the grandfather of antifungals? And what is its MOA

Answer 15

Amphotericin B - inhibits ergosterol (already synthesized by generating pores in the fungal wall

Question 16

What is the spectrum of Amphotericin B?

Answer 16

very broad - Candida, Aspergillus, Zygomyces, Histoplasma, Cryptococcus

Question 17

What are the side effects of Amphotericin B

Answer 17

1. NEPHROTOXICITY - elevated serum creatinine
2. acute infusion related reactions - fever, chills, rigors <– pre-medicate with diphenhydramine (Benadryl), APAP, Meperidine
3. Electrolyte abnormalities - low Mg+, low K+

Question 18

What is the solution to Amphotericin’s awful side effects?

Answer 18

Lipid formulations (Abelcet, Liposomal Amphotericine B- L-AMB)- they have better tolerability and renal protective and you can increase the dose safely
*Expensive

Question 19

The newest class: Echinocandins (capsofungin) are “me too drugs” approved for

Answer 19

Candida infections- resistant to azoles
Refractory ASPERGILLUS infection
Esophageal candidiasis
Febrile neutopenic patients prophylaxis

Question 20

Are the echinocandins avalialbe IV or PO

Answer 20

IV only

Question 21

How safe are Echinocandins?

Answer 21

very safe - it is hepatically cleared so you adjust if liver dysfunction

• -very few drug interactions
• -Excellent for Candida and MOLDS

Question 22

Which pyrimidine analog inhibits DNA and RNA synthesis in fungi and molds?

Answer 22

Flucytosine

Question 23

What is the spectrum of activity of Flucytosine?

Answer 23

Narrow and is active against *Cryptococcus and some Candida spp.

Question 24

Which other antifungal does Flucytosine exhibit synergy with??

Answer 24

Amphotericin B

• combo used especially for Cryptococcal Meningitis
• Don’t use Flucytosine alone - resistance quickly develops

Question 25

Which antibiotic is a prodrug?

Answer 25

Flucytosine (comes from 5-FU in fungus)

Question 26

side effects of Flucytosine

Answer 26

bone marrow toxicity
liver dysfunction
N/V