Antifungals

Question 1

What is the action of Amphotericin B?

Answer 1

binds ergosterol to form pores in membrane that leaks potassium

Question 2

What fungi is Amphotericin B active against?

Answer 2

1. Candida albicans 2. Histoplasma 3. Cryptococcus 4. Coccidioides 5. Blastomyces

Question 3

What are the adverse effects of Amphotericin B

Answer 3

Acute Kidney Injury (accumulates in PCT affecting absorption of Na, Cl), hypotension, anemia. Does not cross BBB or placenta

Question 4

How is Amphotericin B administered?

Answer 4

Slow IV infusion, given with sodium flush before and after to avoid kidney toxicity

Question 5

What is the action of Flucytosine

Answer 5

Converted to 5-flurodeoxyuridine monophosphate in fungal cells, inhibits DNA synthesis by inhibiting thymidylate synthase and RNA synthesis by inhibiting F-deoxyUTP.

Question 6

What are adverse effects of Flucytosine?

Answer 6

Falling neutrophils
Liver dysfunction
Upchuck
Clotting

Question 7

How is Flucytosine used?

Answer 7

Combined with other agents, systemic fungal infections -> broad spectrum agent, can cross BBB

Question 8

What are the 4 azoles?

Answer 8

ketoconazole, fluconazole, voriconazole, posaconazole - AZOLES are assholes! lots of side effects and all teratogenic

Question 9

What azole is used for aspergillus?

Answer 9

voriconazole

Question 10

Which azole has the fewest side effects?

Answer 10

fluconazole

Question 11

What is the mechanism of the azoles?

Answer 11

inhibit C14-alpha-demethylase, which blocks conversion of lanosterol to ergosterol (membrane structure)

Question 12

What are side effects of Fluconazole?

Answer 12

teratogenic, GI effects and skin rash

Question 13

What are side effects of ketonazole?

Answer 13

sex related, hepatotoxicity

Question 14

What are side effects of Voriconazole?

Answer 14

frequent drug interactions (p450), visual and auditory hallucinations

Question 15

What are side effects of posaconazole?

Answer 15

Liver dysfunction, give with high fat meal

Question 16

How is resistance to azoles conferred?

Answer 16

mutation in C14-alpha-demethylase gene so drug can no longer bind to it

Question 17

What are the echinocandins?

Answer 17

caspofungin, anidulafungin

Question 18

What is the mechanism of the echinocandins?

Answer 18

inhibit Beta(1,3)-D-glucan (inhibits cell wall synthesis) which leads to cell lysis

Question 19

What are capsofungin and anidulafungin useful against?

Answer 19

A for aspergillis and C for candida

Question 20

What are adverse effects of echinocandins?

Answer 20

The F’s: fever, flebitis, flushing, and Rash

Question 21

What is the mechanism of Griseofluvin?

Answer 21

accumulates in keritin-containing tissues, disrupts mitotic spindle and fungal mitosis

Question 22

What are the uses of Grisofluvin?

Answer 22

ringworm, dermatophytosis of skin and hair. Give with Grease

Question 23

What are adverse effects of Griseofluvin?

Answer 23

induces P450 drugs, increases metabolism of many drugs

Question 24

How is Griseofluvin administered?

Answer 24

With “grise” – grease. Take with high fat meal

Question 25

What is the mechanism of Terbinafine?

Answer 25

inhibits squalene epoxidase, which block synthesis of ergosterol in cell membrane. "Fungicidal"

Question 26

What are the clinical uses of Terbinafine?

Answer 26

dermatophytoses, onchyomycoses (nails)

Question 27

What are the adverse effects of Terbinafine?

Answer 27

The T's. Taste, Toilet, transaminases (+ visual)

Question 28

What is Nystatin used for?

Answer 28

topical treatment of candida or oral treatment with swishing and spit (minimal oral absorption)

Question 29

What is the mechanism of nystatin?

Answer 29

forms pores in membranes allowing potassium efflux

Question 30

What is the mechanism of Cilopirox?

Answer 30

inhibits transport, leads to decrease in DNA, RNA, and protein synthesis

Question 31

What is Cilopirox used to treat?

Answer 31

Topical use: seborrheic dermatitis (1% solution), tina pedis, tinea corporis, onchyomycoses (8% solution)