Antifungal Drugs

Question 1

type of yeast that can infect the brain and cause high mortality

Answer 1

cryptococcus

Question 2

which fungi are unicellular?

Answer 2

yeast

Question 3

which fungi are multicellular?

Answer 3

moulds

Question 4

which moulds are difficult to tx?

Answer 4

aspergillus

Question 5

what does primary fungal infection mean?

Answer 5

species can proliferate in the absence of opportunity

Question 6

which primary fungal infections are more common in the US?

Answer 6

blastomycosis

histoplasmosis

Question 7

which primary fungal infections are not as common in the US?

Answer 7

coccidiomycosis

paracoccidioiomycosis

Question 8

what is the trend of death d/t fungal infection?

Answer 8

increased since the 1950s/70s to now

30-40% of pts hospitalized die d/t fungal infections today

Question 9

why have deaths d/t fungal infections increased over the years?

Answer 9

• advances in diseases

- advances in medicine (newly immunosuppressed populations and antibiotics create environment for proliferation)

Question 10

polyene drugs:

Answer 10

nystatin

amphotericin B

Question 11

nucleoside analog:

Answer 11

flucytosine

Question 12

azole drugs:

Answer 12

topical: clotrimazole
systemic: fluconazole

Question 13

allylamine drug:

Answer 13

terbinafine

Question 14

echinocandin drug:

Answer 14

micafungin

Question 15

antifungal targets:

Answer 15

• cell membrane
• DNA/RNA synthesis
• cell wall

Question 16

polyenes MOA:

Answer 16

inhibit cell membrane synthesis

Question 17

flucystine MOA:

Answer 17

interrupt DNA/RNA synthesis
converted to fluorouracil and incorporated into RNA
targets thymidylate synthase

Question 18

azoles MOA:

Answer 18

interrupt sterol biosynthesis (cell and mito membrane)

Question 19

micafungin MOA:

Answer 19

inhibit cell wall synthesis

Question 20

which antifungals target the cell membrane?

Answer 20

polyenes
azoles
allylamines

Question 21

what is a suspension dosage?

Answer 21

nystatin liquid, swish and spit or swallow

can be used to tx thrush

Question 22

where does the name Nystatin come from?

Answer 22

two ladies in NY State who discovered it

Question 23

topical polyene absorption

Answer 23

poor oral absorption

used as cream, ointment, and suspensions/powders/tablets

Question 24

SE of amphoTERRIBLE:

Answer 24

infusion related (given IV)
nephrotoxicity (dose and duration related)
electrolyte wasting (chills and rigors)
anemia (Epo production from kidney impaired)

Question 25

ways to mitigate SE with amphotericin?

Answer 25

- give with meperidine (demerol) to reduce chills/rigors - dilute and give with saline (increase perfusion) - combine in lipids (reduce nephrotoxicity)

Question 26

Flucytosine is commonly used with which other antifungal?

Answer 26

amphotericin (can tx cryptococcal)

Question 27

Flucytosine AE:

Answer 27

effects cells that rapidly turnover bone marrow suppression skin GI intolerances

Question 28

Which enzyme converts flucytosine into 5fu?

Answer 28

cytosine deaminase

Question 29

what makes up a fungal cell membrane:

Answer 29

squalene and ergosterol

Question 30

what ratio of cells promotes fungal cell membrane integrity?

Answer 30

ergosterol>>squalene

Question 31

which enzyme converts lenosterol to ergosterol?

Answer 31

demethylase enzyme (aka CYP450 51A1)

Question 32

which enzyme degrades squalene?

Answer 32

squalene epoxidase

Question 33

which enzyme do azoles target?

Answer 33

demethylase (CYP450 51A1)

Question 34

Effect of azoles on other medications?

Answer 34

can impair clearance d/t the inhibition of CYP450 enzymes

Question 35

what type of environment is required for optimal azole absorption?

Answer 35

acidic

Question 36

uses for azole meds?

Answer 36

vulvovaginal candidiasis oropharyngeal candidiasis tinea infections

Question 37

what may be an indication to use allylamines orally?

Answer 37

severe onychomycosis

Question 38

Terbinafine (Lamisil) MOA:

Answer 38

interfere with squalene epoxidase activity (makes membrane unstable)

Question 39

Where does lamisil concentrate?

Answer 39

skin, nails, hair (ONLY really good for nail bed infections)

Question 40

which drug, azoles or allylamines, have more CYP450 interactions?

Answer 40

azoles

Question 41

which drug may be a good alternative to azoles/ampho d/t fewer SE and drug interactions?

Answer 41

echinocandins (micafungin, not a first line therapy)

Question 42

what are mechanisms of resistance?

Answer 42

alteration of binding site develop efflux transporter develop enzyme that destroys drug therapy

Question 43

Griseofulvin (other) MOA:

Answer 43

inhibit mitosis via spindle structure

Question 44

Micafungin MOA:

Answer 44

inhibit beta glucan synthase to halt cell wall synthesis

Question 45

How is tavaborole (kerydin) applied?

Answer 45

nail polish for onychomycosis

Question 46

things to be cautious of with systemic azoles:

Answer 46

- liver function tests - cytochrome interactions - pH absorption