Antifungal

Question 1

What advantages does the lipid amphotericin B formulation have over the traditional formulation? How do ADE change?

Answer 1

Lipid formulation - amphotericin has affinity ergosterol > lipid > cholesterol so serves a reservoir for ampho; reduced risk for infusion reactions and nephrotoxicity

Question 2

Which antifungal can be used for synergy? How does it provide synergy? What happens if it were to be used as monotherapy?

Answer 2

a. Flucytosine –> used with amphotericin B, typically added to therapy only for meningitis
b. Provides synergy by inhibiting DNA/RNA synthesis by competing with uracil
c. If used as monotherapy, RAPID RESISTANCE will occur

Question 3

Know doses of drugs for first line therapy for onychomycosis, vulvovaginal candidiasis, oral thrush.

Answer 3

a. Onychomycosis - Terbinafine (250 mg qd –> fingernail 6 wks, toenail 12 wks)
b. Vulvovaginal candidiasis - Clotrimazole, Miconazole –> OTC
c. Oral thrush - Nystatin (suspension swish and swallow 4x/day)

Question 4

What populations are at highest risk for severe systemic fungal infections?

Answer 4

Immunocompromised (AIDS and chemo)

Question 5

Flucytosine: MOA and main organisms covered

Answer 5

MOA: inhibits DNA/RNA synthesis by competing with uracil

Main organisms: Candida spp., Cryptococcal spp.

Question 6

Griseofulvin: MOA and main organisms covered

Answer 6

MOA: unclear; binds to keratin in skin inhibiting fungal growth, fungistatic
Main organisms: dermatophytes - largely replaced by terbinafine and itraconazole, not active topically