Antifungal

Question 1

MOA: Polyene macrolide? Prototype drug?

Answer 1

Aggregates with ergosterol -> pores and leakage -> increased permeability/leakage of intracellular ions and macromolecules
Amphitericin B

Question 2

Broadest spectrum of action?

Answer 2

Amphotericin B

Question 3

Have intrinsic resistance to amphotericin B?

Answer 3

Candida lusitaniae and Pseudallecheria boydii

Question 4

Most significant toxicity in amphotericin b?

Answer 4

Renal damage (irreversible if >4g cumulative dose)

Question 5

MOA of flucytosine?

Answer 5

Inhibits nucleic acid synthesis

Question 6

FluCytosine spectrum of activity

Answer 6

Cryptococcus, Candida, Chromoblastomycosis

Question 7

Cause of AE in flucytosine?

Answer 7

From metabolism to toxic antineoplastic compound FLUOROURACIL (AEs: usually blood-related)

Question 8

Route of admin for imidazoles? Sample drugs?

Answer 8

Topical; Ketoconazole, Miconazole, Clotrimazole

Question 9

Route of admin for triazoles? Sample drugs?

Answer 9

Can be given centrally/IV, less AEs; Itraconazole, Fluconazole, Voriconazole, Posaconazole

Question 10

Azoles MOA?

Answer 10

Reduced ergosterol synthesis by inhibition of fungal CYP450 enzymes (Imidazoles less fungi-sensitive -> more toxicity)

Question 11

Why is ketoconazole not used systemically anymore?

Answer 11

Greater propensity to inhibit mammalian cytochrome -> less selective

Question 12

Azole of choice for dimorphic fungi: Histoplasma, Blastomyces, Sporothrix, and Aspergillus

Answer 12

Itraconazole

Question 13

Has high oral BA and has widest therapeutic index of thenazoles (safest)

Answer 13

Fluconazole

Question 14

Azole of choice for Cryptococcal meningitis but noactivity against Aspergillus and Candida krusei

Answer 14

Fluconazole

Question 15

PRelevant inhibitor of mammalian CYP3A4?

Answer 15

Voriconazole

Question 16

DOC against Candida sp. and Candida krusei, and against Aspergillus

Answer 16

Voriconazole

Question 17

MOA echinocandins?

Answer 17

Act on fungal cell wall by inhibiting the synthesis of B(1-3) glucan -> disrupted CW -> cell death

Question 18

Empiric tx for febrile neutropenia?

Answer 18

Caspofungin

Question 19

Tx for candidemia and prophylaxis of candida infection in BM transplant?

Answer 19

Micafungin

Question 20

Esophageal and invasive candidiasis?

Answer 20

Anidulafungin

Question 21

Disrupts mitotic spindle and inhibits fungal mitosis? (Fungistatic)

Answer 21

Griseofulvin

Question 22

Duration of tx in griseofulvin for skin and hair infection?

Answer 22

2-6 weeks (never 1 week!)

Question 23

Inhibits epoxidation of squalene -> no ergosterol synthesis (fungicidal)

Answer 23

Terbinafine

Question 24

Tx for dermatophytosis (onchomycosis), given OD for 12 weeks

Answer 24

Terbinafine

Question 25

For oral thrush, vaginal candidiasis, intertriginous candida infxn

Answer 25

Nystatin