Antifungals

Question 1

amphotericin B MOA

Answer 1

cidal
interacts with ergosterol in fungal membrane, results in pore formation that increases permeability which leads to cell death

Question 2

DOC for most systemic fungal infections

Answer 2

Amphotericin B

Question 3

amphotericin B infusion toxicites

Answer 3

chills, fevers, muscle spasms, vomiting, headache

Question 4

amphotericin B cumulative toxicities

Answer 4

powerful nephrotoxic agent (azotemia, BUN and crea)

can lead to irreversible kidney damage

Question 5

MOA for flucytosine

Answer 5

metabolic antagonism of fungal DNA and RNA

converted to 5-fluorouracil which interferes with synthesis

Question 6

DOC for cryptococcus infections

Answer 6

Flucytosine + Amp B (synergistic)

Question 7

Does flucytosine penetrate CNS?

Answer 7

Yes

All flu drugs are good CNS penetrators

Question 8

toxicities of flucytosine

Answer 8

depression of bone marrow, GI disturbances, elevation of AST or ALT

Question 9

MOA for “azole” antifungals

Answer 9

static

inhibits synthesis of ergosterol and eventually inhibition of fungal growth

Question 10

spectrum for ketoconazole

Answer 10

broad spectrum, good for topical infections

Question 11

ketoconazole toxicities

Answer 11

inhibitor of P450 system, gynecomastia and impotence, prolonged QT

Question 12

ketoconazole contraindications

Answer 12

acute or chronic hepatic disease

Question 13

fluconazole penetration

Answer 13

penetrates well into other bodily fluids, particularly CSF

Question 14

Fluconazole in HIV patients?

Answer 14

good for suppressive and/or prophylactic therapy in HIV patients

Question 15

Toxicities of fluconazole

Answer 15

potent inhibitor of CYP2C9, but less drug interactions than other azoles, headache (due to CNS penetration)

Question 16

DOC for aspergillus

Answer 16

voriconazole + amp B

Question 17

voriconazole penetration

Answer 17

moderate CSF penetration

Question 18

voriconazole toxicities

Answer 18

is both metabolized and inhibits P450s (metabolized in reverse order), visual impairment that is reversible

Question 19

spectrum of itraconazole

Answer 19

similar to ketoconazole but has greater activity against aspergillus

Question 20

toxicities of itraconazole

Answer 20

potent inhibitor of CYP3A4, GI effects, N/V/D, abd pain

Question 21

bioavailability of itraconazole

Answer 21

capsules: better absorption with meal or soda

oral solution: better absorbed on empty stomach

Question 22

spectrum of isavuconazonium

Answer 22

mucormycosis and invasive aspergillosis

Question 23

toxicities of isavuconazonium

Answer 23

CYP3A4, nephrotoxicity, dose dependent decrease in QT interval

Question 24

spectrum for posaconazole

Answer 24

aspergillus and candida

Question 25

toxicities of posaconazole

Answer 25

CYP3A4, other toxicities are not well known due to the drug being very new

Question 26

MOA of echinocandins

Answer 26

inhibits synthesis of B(1,3)-D-glucan, which is a major fungal cell wall component

Question 27

what makes caspofungin a good drug?

Answer 27

lack of nephrotoxicity and few drug interactions

Question 28

caspofungin for aspergillosis?

Answer 28

yes, in refractory patients that are resistant to azoles or amp B

Question 29

griseofulvin MOA

Answer 29

static | binds to microtubules of certain fungi and destroys mitotic spindle structure

Question 30

DOC for onychomycosis

Answer 30

griseofulvin

Question 31

route for griseofulvin

Answer 31

ORAL only

Question 32

what is griseofulvin mostly used for

Answer 32

dermatophytosis infections of skin, hair, nails

Question 33

griseofulvin toxicities

Answer 33

headache, disulfuram-like effects, photosensitivity

Question 34

griseofulvin contraindications

Answer 34

acute intermittent porphyria, hepatocellular failure, pregnancy and men 6 months prior to fathering a child

Question 35

terbinafine MOA

Answer 35

cidal | interferes with sterol biosynthesis, squalene monooxygenase

Question 36

route for terbinafine

Answer 36

oral or topical

Question 37

spectrum for nystatin

Answer 37

primarily used for candida infections

Question 38

what are the two polyene antibiotics we learned

Answer 38

amp B and nystatin