Anti-fungals

Question 1

Which drugs inhibit ergosterol synthesis?

Answer 1

azoles, terbinafine

Question 2

Which drugs treat onychomycosis?

Answer 2

fluconazole, itraconazole, terbinafine

Question 3

Which drugs inhibit cyt P450?

Answer 3

azoles, esp ketoconazole

Question 4

Which drugs cause liver dysfunction?

Answer 4

azoles, griseofulvin

Question 5

Describe the formation of ergosterol for fungal membranes.

Answer 5

Squalene–>lanosterol via squalene epoxidase

lanosterol–>ergosterol

Question 6

Describe the formation of nucleic acids in fungus.

Answer 6

precursors–>pyrmidines–>nucleic acid

Question 7

What is the basic MOA of the following anti-fungals?
azoles
terbinafine
flucytosine
griseofulvin
amphotericin B
nystatin

Answer 7

azoles–>inhibit lanosterol–>ergosterol
terbinafine–>inhibits squalene epoxidase
flucytosine–>inhibits DNA/RNA synthesis after becoming 5-FU
griseofulvin–>inhibits microtubule formation
amphotericin B–>forms holes in ergosterol membrane
nystatin–>forms holes in ergosterol membrane

Question 8

What are the important things to know about amphotericin B?

Answer 8

binds ergosterol and forms holes in membrane
allows leakage of electrolytes
good for systemic mycosis, like cryptococcus meningitis

SE: 
nephrotoxicity!
fever/chills
hypotension, hypokalemia
arrhythmias
phlebitis

Question 9

How can you help decrease the nephrotoxicity while taking amphotericin B?

Answer 9

hydrating

taking w/ lipophilic version of amphotericin

Question 10

What are the important things to know about nystatin?

Answer 10

forms holes in ergosterol membrane
VERY potent, so only approved for use topically

used for oral candida, vulvovaginitis, diaper rash

Question 11

What are the important things to know about flucytosine?

Answer 11

flucytosine–>5-FU via cytosine deaminase
5-FU inhibits RNA/DNA synthesis
used w/ amphotericin B for cryptococcal meningitis

can cause bone marrow suppression

Question 12

What do you need to know about the azoles?

Answer 12

inhibits synthesis of ergosterol
inhibit CYTp450–>can cause liver dysfunction and elevated liver enzymes
can mess w/ hormones–>ketoconazole: gynecomastia

Question 13

What are the topical azoles?

Answer 13

clotrimazole

miconazole

Question 14

What are the typical indications for fluconazole?

Answer 14

cryptococcal meningitis, candida

Question 15

What are the usual indications for itraconazole?

Answer 15

blastomyces, coccidioides, histoplasma (dimorphic)

Question 16

Which of the azoles can be used to treat aspergillus?

Answer 16

voriconazole

Question 17

Which one of the azoles can be used for refractory fungi?

Answer 17

posaconazole

Question 18

What are the important things to know about terbinafine?

Answer 18

inhibits squalene epoxidase, decreases ergosterol synthesis

dermatophytoses

Question 19

What is good to know about echinocandins?

Answer 19

inhibits cell wall synthesis by inhibiting formation of beta glucan

• *caspofungin, anidulafungin, micafungin
• *can cause GI, flushing

Question 20

What are the indications for caspofungin?

Answer 20

C-candida, ASP-aspergillosis Fungin

Question 21

What’s the deal with griseofulvin?

Answer 21

interferes w/ microtubule formation
disrupts mitosis
goes to keratin-containing tissues, so it is good for skin infections and tinea

Question 22

What are the side effects of griseofulvin?

Answer 22

teratogenic
carcinogenic
confusion
HA
increases Cytp450 and can increase warfarin metabolism