Antifungals

Question 1

amphoB MOA

Answer 1

binds to ergosterol

Question 2

spectrum (CACEZ)

Answer 2

BROAD

Candida, Aspergillus, cryptococcus, endemics, zygomycetes

Question 3

amphoB adjust for organ dysfxn?

Answer 3

no

Question 4

amphoB toxicity

Answer 4

Nephrotoxicity (TG feedback –> constriction; RTA –> spill electrolytes) loss of H/K/Mg
Anemia
Infusion fever/rigors

Question 5

lipid amphoB

Answer 5

gentler - reduces SE’s by 20x

but less potent

Question 6

indications for amphoB

Answer 6

1st line for:
Crypt. Meningitis
Endemics
Initial tx for Zygomycoses

Question 7

Tx of zygomycetes?

Answer 7

AmB

Question 8

Cryptococcal meningitis 1st line?

Answer 8

AmB

Question 9

Azole MOA

Answer 9

block an enzyme in the ergosterol synth pathway
static for candida
cidal for aspergillus

Question 10

Azole spectrum

Answer 10

Candida (not glabrata/krusei)
Cryptococcus
Endemics

Question 11

big candida problem in the hospital

Answer 11

Glabrata

Question 12

Azoles NOT good for

Answer 12

Aspergillus

Zygomycetes

Question 13

Fluconazole kinetics

Answer 13

Gets where we want it to get
renal elimination
drug interactions: CYP450 inhibitor

Question 14

Fluconazole toxicity

Answer 14

teratogenicity limits in pregnancy

QT prolongation

Question 15

Fluconazole indications

Answer 15

1st line: mucosal candidiasis
1st line: step-down for invasive candidiasis and cryptococcal meningitis
1st line for candida cystitis

Question 16

mucosal candidiasis tx

Answer 16

fluconazole

Question 17

Itraconazole spectrum

Answer 17

More potent against endemic fungi
Candida/Crypto/aspergillus/dermatophytes
Not zygomycetes

Question 18

Itraconazole kinetics

Answer 18

VARIABLE absorption (not sure how much pt will actually get)
depends on acid/food status of stomach
poor CNS/urine distribution
no change for renal dysfunction
BIG TIME CYP450 inhibitor

Question 19

Itraconazole toxicity

Answer 19

more GI than fluconazole
QT prolong
same teratogenicity problem

Question 20

Itraconazole indications

Answer 20

1st line for dermatophytes

1st line step down for endemics

Question 21

Voriconazole spectrum

Answer 21

closer to itra than flu
Aspergillus terreus (not gotten by amphora)
endemics/crypto
not zygomycetes

Question 22

Voriconazole kinetics

Answer 22

Does not get in urine
Yes CNS
No need for food or acid
SHORT half-life
**liver metabolism: CYP2C19 (thus need TDM)
CYP450 inhibitor

Question 23

voriconazole toxicity

Answer 23

most toxic among triazoles
VISUAL photopsia, photosensitivity –> sunburns
more hepatotoxicity

Question 24

Voriconazole indications

Answer 24

1st line: BEST for invasive aspergillosis, fusarium, scedosporium
endemics/cryptococcal meningitis

Question 25

Posaconazole

Answer 25

ZYGOMYCETES + the rest

Question 26

Posaconazole kinetics

Answer 26

need lipids acid needed, better w/food poor CNS, no urine TDM

Question 27

Posaconazole toxicity

Answer 27

OK | ...but less information than other triazoles

Question 28

Posaconazole indications

Answer 28

1st line prophylaxis in HEME malignancy/BMT 1st line ZYGOMYCETES (only other option is AmphoB) 2nd line for other infections (endemics e.g.)

Question 29

Isavuconazole

Answer 29

Same is posaconazole

Question 30

Isavuconazole advantages

Answer 30

``` kinetics: well-absorbed, IV formulation no need for acid or food no need for TDM no change for renal/hepatic dysfunction few drug interactions CYP3A4 ```

Question 31

Isavuconazole SE's

Answer 31

minimal

Question 32

Isavuconazole indications

Answer 32

1st line for aspergillus/zygomycestes, fusarium, scedosporum | 2nd line for candidiasis and endemics

Question 33

flucytosine

Answer 33

inhibits DNA/protein synthesis candida (all) and crypto Nothing else

Question 34

Flucytosine kinetics

Answer 34

oral only CNS and urine excellent no drug interactions change dose for renal dysfxn

Question 35

Flucytosine toxicity

Answer 35

``` life-threatening toxicity with amphoB --> nephrotoxicity Bone marrow suppression Hepatitis *due to accumulation of 5-FC in blood So use TDM ```

Question 36

Flucytosine primary use

Answer 36

cryptococcal meningitis (w/AmphoB) candida cystitis

Question 37

Echinocandin MOA

Answer 37

inhibit B-D-glucan synthase

Question 38

Echinocandin kinetics

Answer 38

IV only Poor CNS/eye/urine minimal toxicity

Question 39

Echinocandin spectrum

Answer 39

CIDAL for all candida (except parapsilosis) Static for Aspergillosis NO cryptococcus/endemics/zygo/dermatophytes

Question 40

Echinocandin indications

Answer 40

1st line for invasive candidiasis (not CNS/eye) Combo w/voriconazole for aspergillosis Prophylaxis for heme malig/BMT

Question 41

Candidiasis

Answer 41

mucosal: topical azoles, oral flucon systemic: AmB, flucon

Question 42

Aspergillosis

Answer 42

Voriconazole AmB Itraconazole (for mild)

Question 43

Cryptococcosis

Answer 43

GOLD STD: AmB + 5-FC | Flucon for mild & suppression

Question 44

Histoplasmosis/Blastomycosis

Answer 44

AmB for severe Itracon for non-life threatening/non-CNS Voricon/Posacon

Question 45

Coccidioidomycosis

Answer 45

AmB for severe Flucon/itracon less effective Flucon for meningitis due to kinetics Voricon/Posacon

Question 46

Dermatophytes

Answer 46

Terbinafine >> Itracon | Terb: fewer SE's and no interactions