Antifungals

Question 1

Name the polyenes

Answer 1

amphotericin B and Nystatin

Question 2

MOA of polyenes

Answer 2

interact with ergosterol in fungal membranes to form artificial “pores” = FUNGICIDAL

Question 3

Polyene resistance mech.

Answer 3

low ergosterol content in cell membrane

Question 4

What is Amphotericin B used for?

Answer 4

Aspergillus, Candida, Cryptococcus, Histoplasma, Mucor, Sporothrix

Question 5

What is the broadest spectrum antifungal on the market?

Answer 5

Amphotericin B

Question 6

What antifungal is used in combo with flucytosine to treat candida and cryptococcus?

Answer 6

Amphotericin B

Question 7

How is nystatin used?

Answer 7

TOPICALLY

too toxic for systemic use

Question 8

How is Amphotericin B administered?

Answer 8

slow IV infusion
poor CNS penetration (requires intrathecal admin. in CNS infection)
slow clearance and t1/2=2 wks

Question 9

How is Amphotericin B toxicity reduced?

Answer 9

liposomal preparation

Question 10

Polyene S.E.?

Answer 10

dose-dependent nephrotoxicity

Question 11

Most common SE of Amphotericin B?

Answer 11

severe fever and chills
tx with aspirin, or acetapminophen, or corticosteriods, or Meperidine
*also SE: rhinocerebral phycomycosis

Question 12

What drug can cause oral candidiasis?

Answer 12

aerosolized beclomethasone (asthma)

Question 13

MOA of azoles?

Answer 13

fungicidal: interfere with synthesis of ergosterol (aka 14alpha demethylase, a CYP450!)

Question 14

Azole resistance?

Answer 14

decreased intracellular accumulation of azoles

Question 15

Ketoconazole use?

Answer 15

co-DOC for paracoccidioides, backup for blastomycoses and histoplasma

Question 16

Fluconazole use?

Answer 16

DOC for esophageal and invasive candidiasis and coccidioidomycoses
prophylaxis for cryptococcal meningitis

Question 17

Itraconazole use?

Answer 17

DOC in blastomycoses, sporotrichoses, aspergillosis, backup for other mycoses

Question 18

Voriconazole use?

Answer 18

same as Itraconazole

DOC in blastomycoses, sporotrichoses, aspergillosis, backup for other mycoses

Question 19

Clotrimazole and miconazole use?

Answer 19

TOPICAL–> candida, dermatophytic infections

Question 20

Azole admin?

Answer 20

oral (except clotrimazole and miconazole)

Question 21

How does antacid use affect ketonazole absorption?

Answer 21

decreases

Question 22

How does food intake affect itraconazole absorption?

Answer 22

increases

Question 23

Drug interactions with azoles?

Answer 23

YES because it inhibits the P450s

Question 24

SE of azoles?

Answer 24

decreased synthesis of steriods (cortisol, testosterone)–> decreased libido, gynecomastia, menstrual irregularities
increase LFTs
Rare hepatotoxicity

Question 25

Flucytosine MOA?

Answer 25

activated by fungal cytosine –> 5FU –> triphosphorylation–> incorporated into fungal RNA
5FU–> 5-Fd-UMP–> inhib. thymidylate synthase–> decrease thymine (DNA)

Question 26

Flucytosine resistance?

Answer 26

YES, if used alone

Question 27

Flucytosine use?

Answer 27

USE WITH AMPHOTERICIN B

in severe cadidal and cryptococcal infections (enters CNS)

Question 28

Flucytosine SE?

Answer 28

bone marrow suppression

Question 29

Griseofulvin use?

Answer 29

active only against dermatophytes
ORAL
**distributes only where keratin is

Question 30

Griseofulvin SE?

Answer 30

Disulfiram like rxn

Question 31

Terbinafine use?

Answer 31

active only against dermatophytes

*may be superior to Griseofulvin in onychomyces

Question 32

Terbinafine MOA?

Answer 32

inhib. squalene epoxidase–> decreases egosterol

Question 33

Terbinafine SE?

Answer 33

GI distress, rash, headache, increased LFTs, hepatotox.

Question 34

Caspofungins MOA?

Answer 34

block glucan synthesis (cell wall)

Question 35

Name one Caspofungins

Answer 35

Micafungin

Question 36

Micafungin use

Answer 36

invasive candidiasis and aspergillosis esp. in HIV pts

Question 37

Caspofungin SE

Answer 37

GI distress, flushing