Antifungals

Question 1

What is the DOC for ALL systemic fungal infections?

Answer 1

Amphotericin B

Question 2

Which two antifungal medications have CNS penetration?

Answer 2

• Flucytosine

- Fluconazole

Question 3

What is the MOA of Amphotericin B? How does this contribute to its two most important characteristics?

Answer 3

Creates pores in ergosterol = leakage

• Broad spectrum
• CIDAL

Question 4

What is the primary toxicity associated with Amphotericin B? How does this affect its use as a treatment (think goal)?

Answer 4

VERY nephrotoxic
- If kidney dysfunction present, continue until fungal load is decreased then STOP and switch… (if no kidney issues, can continue)

Question 5

What is the DOC for Cryptococcus infections?

Answer 5

Flucytosine + Amphotericin B

Question 6

What is the MOA of Flucytosine?

Answer 6

Inhibits DNA and RNA synthesis

Question 7

What is the primary toxicity associated with Flucytosine?

Answer 7

Bone marrow suppression

Question 8

How do Amphotericin B and Flucytosine differ from the Azoles? What are the four important Azoles we discussed in class?

Answer 8

• Amphotericin B and Flucytosine = CIDAL
• Azoles = STATIC - only use in IC if nothing else is available

Azoles: Ketoconazole, Fluconazole, Voriconazole, Itraconazole

Question 9

What is the preferred Azole for antifungal treatment, and why?

Answer 9

Fluconazole because has CNS penetration and LESS toxic that Ketoconazole

Question 10

What is the MOA of ALL Azoles?

Answer 10

Inhibit ergosterol synthesis

Question 11

What is the primary toxicity associated with Fluconazole?

Answer 11

Headaches

Question 12

What are the three primary toxicities associated with Ketoconazole?

Answer 12

• Drug interactions (inhibits CYP3A4)
• Gynecomastia
• QT prolongation

Question 13

What is the DOC for Aspergillus infections? What is the alternative treatment option, and why would this be used?

Answer 13

Voriconazole + Amphotericin B

- Caspofungin + Amphotericin B used if non-responsive to Voriconazole (not uncommon)

Question 14

What is the primary toxicity associated with Voriconazole?

Answer 14

Visual issues

Question 15

What is the primary toxicity associated with Itraconazole? What other antifungal medication is it similar to?

Answer 15

Drug interactions

- Similar to Ketoconazole

Question 16

When prescribing Itraconazole, what should always be considered?

Answer 16

Bioavailability (capsules vs. oral solutions) should NOT be mixed

Question 17

What are the three Echinocandins, and how do they differ from the Azoles? What is the MOA of these medications?

Answer 17

Echinocandins: Caspofungin, Micafungin, Anidulafungin

• MOA: inhibit B(1,3)-D-glucan synthesis in cell wall
• All are CIDAL (due to cell WALL activity)

Question 18

What is the DOC for onychomycosis, and WHY?

What is an alternative treatment for onychomycosis, and when would this be considered?

Answer 18

Griseofulvin because binds to keratin

- Alternative is Terbinafine if oral is NOT tolerated (administered as topical, G is only oral)

Question 19

What is the MOA of Griseofulvin?

Answer 19

Inhibits microtubules

Question 20

What are the four primary toxicities associated with Griseofulvin? Under what three conditions is it contraindicated?

Answer 20

VERY TOXIC (GI issues)

• GI issues
• Photosensitivity
• HA
• Disulfiram-like effect

Contraindicated if porphyria, pregnant, autoimmune disorder

Question 21

What is the MOA of Terbinafine?

Answer 21

Inhibits ergosterol synthesis (just like Azoles)

Question 22

What is the DOC for Candidal infections?

Answer 22

Nystatin