Azoles (Antifungal)

Question 1

What is the MOA of azoles?

Answer 1

inhibit ergosterol synthesis (important component of fungal cell membranes)

Question 2

What are 5 common azoles medications?

Answer 2

Fluconazole, Itraconazole, Voriconazole, Posaconazole, Isavuconazole

Question 3

Which organ metabolizes azoles and what are their main toxicity?

Answer 3

• metabolized in the liver

Main toxicity = elevated LFTs

Question 4

What is the drug-of-choice for non-severe Candida infections?

Answer 4

Fluconazole

Question 5

Which azole has the best overall bioavailability?

Answer 5

Fluconazole

Question 6

Which azole has the best activity against Histoplasmosis?

Answer 6

Itraconazole

Question 7

Does Itraconazole have good CNS penetration?

Answer 7

NO

Question 8

What is the black box warning for Itraconazole?

Answer 8

Can cause or worsen CHF in predisposed patients because it is a NEGATIVE INOTROPE

Question 9

What is the drug of choice for Invasive Aspergillosis?

Answer 9

Voriconazole

Question 10

What organism is Voriconazole NOT effective in treating?

Answer 10

Mucomycosis

Question 11

Besides liver toxicity, what is the major toxicity seen with Voriconazole use?

Answer 11

EYE toxicity –> transient visual changes (common) and visual hallucinations (rare)

Question 12

Which two azoles have coverage against mucomycosis?

Answer 12

Posaconazole and Isavuconazole

Question 13

Why is Posaconazole typically a 2nd-line/salvage treatment for most severe fungal infections?

Answer 13

ONLY available PO and must be given with fatty foods for best absorption

• takes 1 week to reach steady-state levels = not suitable for ACUTE treatment of severe fungal infections

Question 14

Which azole is the newest currently available, boasting broad-spectrum fungal coverage and having better acute treatment ability vs Posaconazole?

Answer 14

Isuvaconazole