Antifungals

Question 1

Amphotericin B

Answer 1

Broadest spectrum of all antifungals

MOA: binds to ergosterol in fungal cell membrane and forms pores

Rx: major systemic fungal infections (Candida (y), Cryptococcus (y), Aspergillus (m), Histoplasma (m))

Resistance: possible w/ ↓ ergosterol concentration

SE: nephrotoxicity (↓ perfusion), infusion-related rxn (flu-like symptoms)

Liposomal-packaged formulation is less toxic

Question 2

Ketoconazole

Answer 2

Azole
MOA: bind to enzyme that converts lanosterol to ergosterol –> “leaky” cell membrane

Rx: broad antifungal spectrum (yeast, systemic mycoses, dermatophytes)

Resistance: efflux pumps, mutations in target enzyme, ↓ ergosterol content

SE: GI disturbances, P450 interactions

Question 3

Fluconazole

Answer 3

Azole (highest Tx index)
MOA: bind to enzyme that converts lanosterol to ergosterol –> “leaky” cell membrane

Rx: candidiasis, cryptococcosis, coccidiomycosis (2° w/ other systemic infections)

Resistance: efflux pumps, mutations in target enzyme, ↓ ergosterol content

SE: GI disturbances, P450 interactions

Question 4

Itraconazole

Answer 4

Azole (NO CNS PENETRATION)
MOA: bind to enzyme that converts lanosterol to ergosterol –> “leaky” cell membrane

Rx: broad antifungal spectrum (yeast, systemic mycoses, dermatophytes)

Resistance: efflux pumps, mutations in target enzyme, ↓ ergosterol content

SE: GI disturbances, P450 interactions (major drug interactions)

Requires ↓ gastric pH

Question 5

Voriconazole

Answer 5

Azole
MOA: bind to enzyme that converts lanosterol to ergosterol –> “leaky” cell membrane

Rx: 1° Tx for aspergillosis

Resistance: efflux pumps, mutations in target enzyme, ↓ ergosterol content

SE: visual impairments, P450 interactions

Question 6

Posaconazole

Answer 6

Azole (Broadest activity spectrum)
MOA: bind to enzyme that converts lanosterol to ergosterol –> “leaky” cell membrane

Rx: Candida, Aspergillus, mucormycoses, others

Resistance: efflux pumps, mutations in target enzyme, ↓ ergosterol content

SE: GI disturbances, P450 interactions (major drug interactions)

Question 7

Flucytosine

Answer 7

Cytosine Analog
MOA: disrupts protein and NA synthesis

Rx: Cryptococcus, Candida (Always ComboTx)

Resistance: altered flucytosine metabolism

SE: BM suppresion

Question 8

Caspofungin

Answer 8

Echinocandin
MOA: inhibit synthesis of B-glucans (needed for fungal cell walls)

Rx: Candida, Aspergillus (fungi w/ high levels of B-glucans)

SE: low toxicity!

IV administration only

Question 9

Micafungin

Answer 9

Echinocandin
MOA: inhibit synthesis of B-glucans (needed for fungal cell walls)

Rx: Candida, Aspergillus (fungi w/ high levels of B-glucans)

SE: low toxicity!

IV administration only

Question 10

Anidulafungin

Answer 10

Echinocandin
MOA: inhibit synthesis of B-glucans (needed for fungal cell walls)

Rx: Candida, Aspergillus (fungi w/ high levels of B-glucans)

SE: low toxicity!

IV administration only

Question 11

Griseofulvin

Answer 11

Oral agent
Rx: Dermatophyte infections

MOA: interferes w/ microtubule function

concentrates in keratin precursor cells

Tx takes weeks -> months

SE: HA, GI distress, hepatotoxicity

Question 12

Terbinafine

Answer 12

Allylamine
MOA: inhibit squalene epoxidase (inhibit ergosterol synthesis)

Rx: onychomycosis

Available both topically and orally

concentrates in keratin precursor cells

SE: HA, GI distress, elevated liver enzymes

Question 13

Nystatin

Answer 13

Topical Antifungal (creams, suppositories, or oral suspension [rinse])
MOA: binds to ergosterol in fungal cell membrane and forms pores

Rx: Candida
(oropharyngeal and vaginal)

Question 14

Clotrimazole

Answer 14

Topical Azole

Rx: vulvovaginal candidiasis, dermatophyte infections, oral thrush (lozenge)

Question 15

Micronazole

Answer 15

Topical Azole

Rx: vulvovaginal candidiasis, dermatophyte infections, oral thrush (lozenge)

Question 16

Natrifine

Answer 16

Topical Allylamine

Rx: tinea cruris (jock itch), tinea corporis (ring worm)