Test 3: antifungals

Question 1

Most antifungals are —

Answer 1

fungistatic
work better on actively growing organisms

need host immune system to clear out infection

Question 2

most antifungals target — in the cell membrane of fungi

Answer 2

ergosterol

(similar to cholesterol in vertebrates cells)

Question 3

what are some polyenes antifungals

Answer 3

amphotericin B (fungizone)

Question 4

amphotericin B works by

Answer 4

irreversibly binds to ergosterol in fungal plasma membrane

forms pore/channel that alter cell membrane permeability

polyenes antifungal
broad spectrum- can get into BBB if injected intrathecally

Question 5

can amphotericin B get into CNS

Answer 5

Does not efficiently penetrate CNS but yes if ingected intrathecally

broad spectrum antifungal that irreversibly binds to ergosterol in plasma membrane and forms pores

Question 6

adverse effects of amphotericin B

Answer 6

nephrotoxicity- binds to cholesterol accidently

fevers, chills, muscle spasms

Question 7

flucytosine works by

Answer 7

antifungal antimetabolite

prodrug activated by fungal cells by cytosine deaminase this leads to formation of F-dump which inhibits thymidylate synthase which will inhibit DNA synthesis (cells can’t divide)

water soluble, distributes throughout the body and brain

Question 8

Flucytosine is a prodrug activated by fungal cells by cytosine deaminase this leads to formation of — which inhibits — which will inhibit DNA synthesis (cells can’t divide)

Answer 8

F-dump
thymidylate synthase

antifungal- can get into brain easily

Question 9

adverse effects of flucytosine

Answer 9

toxic if drug is metabolized into toxic metabolites in the GI tract

Bone marrow toxicities, anemia,
leukopenia, thrombocytopenia

Question 10

what are some azoles

Answer 10

imidazole: ketoconazole

triazole: fluconazole, itraconazole

antifungals- inhibit fingal cytochrome P450 enzymes

Question 11

method of action for azole drugs

Answer 11

Reduce ergosterol synthesis by inhibiting fungal cytochrome P450 enzymes

imidazole: ketoconazole
Triazole: fluconazole

Question 12

ketoconazole

Answer 12

imidazole antifungals

Less selective for fungal cytochrome P450 than newer azoles (more side effects)

used for yeasts and dimorphic fungi

does not penetrate blood brain barrier

eliminated in the liver

Question 13

does ketoconazole get into CNS?

Answer 13

no- poor penetration

Less selective for fungal cytochrome
P450 than newer azoles (more side
effects)

imidazole antifungal: used to treat yeasts and dimorphic fungi

Question 14

adverse effects of ketocanzole

Answer 14

Inhibits mammalian Cytochrome P450 enzymes
– Suppresses adrenal and gonadal steroid synthesis
– infertility, menstrual irregularities

GI: anorexia, vomiting and nausea

imidazole antifungal
inhibit fungal P450
does NOT get into brain

Question 15

can fluconazole get into brain

Answer 15

yes- small and water soluble

antifungal- 100 x more potent then Ketoconazole

Question 16

adverse effects on fluconazole

Answer 16

can interact with other drugs

but few side effects

triazole antifungal: that can cross BBB

Question 17

which triazole antifungal works well against aspergillus

Answer 17

itrazonazole

fluconazole is not effective

Question 18

itrazonazole

Answer 18

triazole antifungal

poor penetration into CNS- lipid soluble
works for aspergillus

eliminated in the liver

Question 19

can itrazonazole get into brain

Answer 19

poor penetration

triazole antifungal- used for aspergillus

Question 20

how is ketoconazole eliminated

Answer 20

liver

Question 21

how is itrazonazole eliminated

Answer 21

liver

Question 22

how is fluconazole eliminated

Answer 22

kidney

Question 23

— are antifungals that can be given systemically to treat skin infections

Answer 23

Griseofulvin (Fulvicin, Grifulvan)

Terbinafine

Question 24

how does griseolfulvin work

Answer 24

disrupts fungal microtubules- inhibit mitosis

used for skin infection

Question 25

adverse effects of griseolfulvin

Answer 25

myelosupression, hepatitis
skin rash
vomiting, diarrhea, anorexia

antifungal that disrupts fungal microtubules and inhibits mitosis
used for skin infections- keratinized tissue

Question 26

Terbinafine works by

Answer 26

Interferes with ergosterol synthesis and prevents fungal growth

Inhibits fungal squalene monooxygenase- no effect on P450 system

persists in skin & adipose > 30 days

metabolized by liver and cleared in urine

Question 27

terbinafine works by inhibiting

Answer 27

yeast squalene monooxygenase

prevents formation of ergosterol synthesis