Antifungals

Question 1

What antifungal class does amphotericin B belong to?

Answer 1

polyene antifungal

Question 2

How does amphotericin B achieve its cidal activity?

Answer 2

binds to ergosterol to form pores

Question 3

What is the DOC for most systemic antifungal infections?

Answer 3

amphotericin B

Question 4

Does amphotericin B have CNS activity?

Answer 4

No

Question 5

If a patient is receiving an amphotericin B infusion, what immediate side effects would you expect to see?

Answer 5

Shake and bake sxs

Question 6

does the presence of acute side effects during amphotericin B infusion warrant a dose change?

Answer 6

no, you can lower the rate

Question 7

how long is the course of tx for amphotericin B?

Answer 7

6wks to 4 months

Question 8

describe the long-term side effects of amphotericin b…

Answer 8

extremely nephrotoxic

elevated BUN and serum creatinine (azotemia)

Question 9

What is flucytosine converted to in the body, and what does it act against?

Answer 9

converted to 5-F-U, acts against DNA/RNA synthesis

Question 10

What is the DOC for cryptococcus infections?

Answer 10

Flucytosine + amphotericin B

Question 11

Flucytosine acts against cryptococcus neoformans. What else is it active against?

Answer 11

candida, aspergillus fumigatus, sporotrichum

Question 12

What is a serious side effect of flucytosine?

Answer 12

depression of bone marrow

Question 13

What labs could be elevated during flucytosine tx? Are they concerning? Why?

Answer 13

ALT, AST elevation

Reversible upon discontinuation of drug

Question 14

What do Azole drugs inhibit? does this lead to static or cidal activity?

Answer 14

inhibit ergosterol

static

Question 15

describe the tissue distribution of ketoconazole

Answer 15

widely distributed

Question 16

describe the spectrum of ketoconazole…

Answer 16

broad spectrum antifungal

Question 17

what does ketoconazole inhibit, leading to what adverse effects?

Answer 17

P450 inhibitor, has many drug interactions

Question 18

what are 2 major adverse effects of ketoconazole?

Answer 18

1. gynecomastia and impotence due to inhibited adrenal and testicular fx
2. prolonged QT

Question 19

What contraindicates the administration of ketoconazole?

Answer 19

acute or chronic hepatic disease

Question 20

under what circumstances should oral ketoconazole administration be considered?

Answer 20

only when no other antifungal therapy can be used

Question 21

does fluconazole have good CNS penetration?

Answer 21

yes

Question 22

Which azole antifungal makes a good suppressive or prophylactic therapy for HIV/AIDS patients?

Answer 22

fluconazole

Question 23

which CYP does fluconazole inhibit, and should that concern you?

Answer 23

CYP2C9. not concerning due to limited nature of CYP2C9 activity compared to ketoconazole’s CYP450 activity

Question 24

Can amphotericin B be administered w/ aminoglycosides? why?

Answer 24

with caution due to synergistic nephrotoxicity

Question 25

when giving fluconazole for suppresive therapy, describe the duration of tx.

Answer 25

lifelong or until CD4 count elevates

Question 26

what is the most common side effect of fluconazole?

Answer 26

headache

Question 27

what is the DOC for aspergillus infection?

Answer 27

Voriconazole + ampho B "VORacious AMPHOtite for asparagus"

Question 28

voriconazole + ampho B is the DOC for aspergillosis. what else does voriconazole treat?

Answer 28

esophageal candidiasis salvage tx of scedosporium and fusarium sp.

Question 29

Voriconazole is metabolized greatest by CYP2C19. But Voriconazole also inhibits P450s. explain how it can still be metabolized by P450 enzymes...

Answer 29

CYP2C19 has the greatest action against voriconazole, least inhibited by voriconazole

Question 30

What is a major adverse effect of voriconazole?

Answer 30

Can cause reversible visual impairment

Question 31

Describe the spectrum of itraconazole

Answer 31

similar spectrum to ketoconazole and fluconazole but with greater activity against aspergillus

Question 32

what are the adverse reactions of itraconazole?

Answer 32

GI upset, NV... CYP3A4 inhibition

Question 33

Describe the bioavailability of itraconazole as capsules...

Answer 33

40-55% on empty stomach, 90-100% w/ meal or cola

Question 34

describe the bioavailability of itraconazole as an oral solution

Answer 34

55% w/ meal, and 72% under fasting conditions

Question 35

What 3 species of | fungus does isavuconazonium tx?

Answer 35

aspergillus, mucor, rhizopus

Question 36

Does isavuconazonium have drug interations?

Answer 36

yes, substrate for and moderate 3A4 inhibition

Question 37

What 2 adverse effects can occur w/ isavuconazonium administration...

Answer 37

Nephro decrease QT

Question 38

When is isavuconazonium contraindicated?

Answer 38

pt. c family hx of short QT syndrome

Question 39

describe the sprectrum of posaconazole...

Answer 39

tx of aspergillus and candida

Question 40

does posaconazole interact w/ other drugs?

Answer 40

yes--3A4 substrate and inhibitor

Question 41

what antibiotic can echinocandins be compared to?

Answer 41

these drugs are the "fungal PCN"

Question 42

why is caspofungin known as a "penicillin of antifungals"

Answer 42

because it is cidal and inhibits cell wall synthesis

Question 43

does caspofungin come w/ drug interactions or nephrotoxicity?

Answer 43

no

Question 44

when should you consider caspofungin in refractory patients?

Answer 44

for invasive aspergillosis w/ azole/ampho b resistant fungi

Question 45

what side effects should you educate pts on w/ caspofungin administration?

Answer 45

elevated AST/ALT, histamine release/flushing, HA, Chills, GI

Question 46

how do echino candins work?

Answer 46

inhibit cell wall synthesis of b(1,3)-D-glucan

Question 47

What are the topical antifungals?

Answer 47

grisofulvin, terbinafine, nystatin

Question 48

What diseases do topical antifungals like griseofulvin, terbinafine and nystatin treat?

Answer 48

dermatophytosis, onychomycosis

Question 49

what is the DOC for onychomycosis and why?

Answer 49

griseofulvin--binds to keratin

Question 50

what are major adverse effects of griseofulvin?

Answer 50

Disulfiram-like effects, ohotosensitivity, GI sxs, headache, CNS

Question 51

what contraindicates the use of griseofulvin?

Answer 51

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

Question 52

what is the moa of terbinafine?

Answer 52

inhibits ergosterol synthesis by inhibiting squalene epoxidase

Question 53

where does terbinafine tend to concentrate?

Answer 53

the nail

Question 54

what other drug can nystatin be compared to and why?

Answer 54

ampho b, both polyenes

Question 55

what is the most common use for nystatin?

Answer 55

candidal infx

Question 56

nystatin is not absorbed where?

Answer 56

GI tract, skin, or mucous membranes

Question 57

Because nystatin has poor GI and skin absorption, what can it be used for?

Answer 57

PO adminstration for GI and skin candida infx

Question 58

which antifungals are cidal?

Answer 58

ampho b nystatin terbinafine caspofungin