Block 4: Anti-Fungals

Front 1

name five classes of drugs that work on fungal cell membranes

Back 1

1. polyenes
2. azoles
3. allylamines
4. pyridones
5. echinocandins

Front 2

almost every polyene contains a __ moiety

Back 2

mycosamine

Front 3

name six fungi susceptible to the polyenes

Back 3

histo
crypto
blasto
coccidiodies
candida
sporothrix

Front 4

polyene MOA

Back 4

bind sterols in both serum and cell membranes -> membrane structure perturbed -> leakage of cell components and altered membrane transport

Front 5

polyene method of selectivity

Back 5

principal fungal membrane sterol is ergosterol, in us it is cholesterol

Front 6

name the two most frequently used polyenes

Back 6

Nystatin
Amphotericin B

Front 7

if nystatin is virtually insoluble, what do we use it for?

Back 7

superficial infections and infections of GI tract (GI fungi? how on earth do you diagnose that?)

Front 8

which is more potent, amphotericin B or Nystatin,

Back 8

amphotericin B- soluble enough for IV admin

Front 9

what are liposomal preparations of amphotericin B

Back 9

combine liposomal amphotericin B with amphotericin B lipid complex - give larger volumes of distribution and decreased renal toxicity (good but expensive)

Front 10

clotrimazole
fluconazole
itraconazole
ketoconazole
miconazole
sertaconazole
ticonazole
voriconazole
gluconazole

Back 10

the azoles- imidazole and triazole antifungals

Front 11

azole MOA

Back 11

inhibits 14-alpha-demethylase (a P450 involved in ergosterol biosynthesis) -> makes membranes w/ altered permeability

Front 12

azole method of selectivity

Back 12

fungal sterol biosynthesis is more sensitive to inhibition than mammalian synthesis

Front 13

miconazole is given ...
ketoconazole, fluconazole, itraconazole are given...

Back 13

topical
orally

Front 14

___ can be used for oral treatment of infections of nails and is the azole drug of choice for tx of dermatophytoses and onychomycosis

Back 14

itraconazole

Front 15

___ is drug of chice for treatment of invasive aspergillosis

Back 15

voriconazole

Front 16

___ has good CNS penetration and is superior for the tx of AIDS associated cryptococcal meningitis

Back 16

gluconazole

Front 17

what is the advantage of using the azoles over amphotericin B

Back 17

they are metabolized primarily by liver- can be given to patients w/ impaired renal function

Front 18

do azoles induce or inhibit CYP3A4

Back 18

inhibit, just like the polyenes

Front 19

___ inhibits other mammalian P450s and reduces adrenal and gonadal steroid biosynthesis

Back 19

ketoconazole

Front 20

___ can precipitate CHF in some patients

Back 20

itraconazole

Front 21

method of resistance to azoles

Back 21

1. overproductions of 14-alpha-demethylase
2. overexpression of MDR-like efflux pump

Front 22

name three allylamines

Back 22

naftafine
terbinafine
butenafine

Front 23

allylamine MOA

Back 23

inhibits fungal squalene epoxidase

Front 24

allylamines when used topically are effective in tx of...
when used orally...

Back 24

tinea infection

cutaneous tinea infections, cutaneous candidiasis

Front 25

___ is a pyridone antifungal agent that inhbits uptake of essential extracellular nutrients

Back 25

ciclopirox olamine

Front 26

only approved drug for topical tx of dermatophyte infection of hair and nails

Back 26

ciclopirox olamine

Front 27

___ is an echinocandin noncompetititve inhibitor of beta-(1,3)-glucan synthase

Back 27

caspofungin

Front 28

___ is used for treatment of invasive aspergillosis in patients refractory to amphotericin B and for esophageal candidiasis

Back 28

caspofungin

Front 29

___ is a cytosine analogue substituted in the 5-position of the pyrimidine ring with fluorine and inhibits fungal nucleic acid synthesis

Back 29

flucytosine

Front 30

when is flucytosine used

Back 30

only in combo w/ amphotericin B because resistance occurs frequently

Front 31

flucytosine MOA

Back 31

metabolized by cytosine deaminase ->
5-fluorouracil ->
incorporated into fungal RNA

also, FdUMP inhibits thymidylate synthetase -> blocks de novo synthesis of dTMP

Front 32

flucytosine method of selectivity

Back 32

compared to fungal deaminase activity, mammalian activity is very low

Front 33

flucytosine route of admin

Back 33

orally

Front 34

name a fungal mitotic inhibitor

Back 34

griseofulvin

Front 35

___ is an insolube compound effective in tx of fungal infection of skin, hair, nails caused by epidermophyton, micosprum and trichophyton

Back 35

griseofulvin

Front 36

griseofulvin is ineffective against...

Back 36

candida

Front 37

griseofulvin MOA

Back 37

disrupts microtubule formation

Front 38

griseofulvin method of selectivity

Back 38

unknown

Front 39

external infections are most responsive to __ therapy with griseofulvin, but...

Back 39

oral
but...it isn't a major metabolite- it must be converted to 6-demethylgriseofulvin and is more absorbed if taken with a fatty meal
(take griseofulvin and eat some Greasy pizza)

Front 40

griseofulvin absorption is inhibited from the gut by...

Back 40

barbituates