Antifungal Pharmacology

Front 1

What are the 4 major classes of antifungal drugs?

Back 1

alter cell membrane permeability
block nucleic acid snthesis
disrupt microtubule function
disrupt fungal cell wall

Front 2

what are the major drugs that affect fungal cell membrane permeability?

Back 2

polyenes
azoles
allylamine and benzylamine

Front 3

what are the major drugs that block fungal nucleic acid synthesis?

Back 3

flucytosine

Front 4

what are the drugs that disrupt fungal microtubule function?

Back 4

griseofulvin

Front 5

what are the drugs that disrupt fungal cell wall?

Back 5

echinocandins

Front 6

which antifungals can be used for subcutaneous and systemic mycoses?

Back 6

amphotericin B
flucytosine
azoles
echinocandins

Front 7

what is amphotericin B?

Back 7

polyene antibioitic
first choice for systemic mycoses

Front 8

what is the MOA of amphotericin B?

Back 8

bind to ergosterol in fungal cell membranes to form pores --> electrolytes and small molecules leak --> DEATH

Front 9

what are the pharmokinetics of amphotericin b?

Back 9

highly insoluble, poorly absorbed
must be given IV
low penetration into CSF

Front 10

when is amphotericin B used?

Back 10

doc for systemic mycoses
widest spectrum
aspergillus, candida albicans, cryptococcus, histoplasma, mucor

Front 11

what are the infusion related adverse effects of amphotericin B?

Back 11

fever, chills, muscle spasms, vomiting, headache, hypotension

Front 12

how can the infusion related adverse effects of amphotericin B be attenuated?

Back 12

slowing infusion rate or decreasing daily dose
pre-medication w/ antihistamines, glucocorticoids, antipyretics, meperidine

Front 13

what are the adverse effects of amphotericin b?

Back 13

renal impairment
anemia due to damaged tubular cells

Front 14

what can intrathecal admin of amphotericin B cause?

Back 14

seizures and neurological damage

Front 15

what is the advantage of lipid formulations of amphotericin b?

Back 15

less nephrotoxicity

Front 16

what is flucytosine?

Back 16

synthetic pyrimidine antimetabolite

Front 17

when is flucytosine used?

Back 17

only in combination w/ amphotericin for treatment of systemic mycoses and meningitis

cryptococcus neoformans and candida

Front 18

what is the moa of flucytosine?

Back 18

taken up in fungal cells via enzyme cytosine permease
converted to f-FdUMP which inhibits thymidylate synthetase - blocks synth of dTMP

Front 19

what are the adverse effects of flucytosine?

Back 19

result from metabolism to 5-flurouracil (affects intestinal flora)
bone marrow suppresion

Front 20

how are azoles classified?

Back 20

imidazoles
triazoles

Front 21

what are the imidazoles?

Back 21

ketoconazole
miconazole
clotrimazole

Front 22

what are the triazoles?

Back 22

itraconazole
fluconazole
voriconazole
posaconazole

Front 23

what is the moa of azoles?

Back 23

inhibits enzyme that converts laosterol to ergosterol = disrupts membrane function and increases permeability

Front 24

what is the difference between imidazoles and triazoles?

Back 24

imidazoles are less specific than triazoles

Front 25

what are the adverse effects of azoles?

Back 25

minor GI upset

Front 26

what are adverse effects of ketoconazole?

Back 26

decrease plasma testosterone levels --> gynecomastia, decreased libido, loss of potency in men, menstrual irregularities in women
high doses inhibit adrenal steroid synthesis and decrease plasma cortisole

Front 27

what is the moa of ketoconazole

Back 27

inhibits mammalian cytochrome P450 enzymes, CYP3A4

Front 28

what are the PK of ketoconazole?

Back 28

best absorbed at low gastric pH
poor penetration into CSF

Front 29

when is ketoconazole used?

Back 29

superficial mycoses

Front 30

what are the PK of fluconazole?

Back 30

good csf penetration
high oral bioavailability

Front 31

what liver enzymes does fluconazole interact with?

Back 31

moderate inhibitor of CYP3A4
strong inhibitor of CYP2C9 - can increase plasma levels of phenytoin, zidovudine and warfarin

Front 32

when is fluconazole used?

Back 32

doc in espophageal, oropharyngeal, vulvovaginal candidiases
doc for coccidoides

Front 33

when is fluconazole used prophylactically?

Back 33

in criptoccocal meningitis

Front 34

when is fluconazole ineffective?

Back 34

aspergillus or other filamentous fungi

Front 35

how is itraconazole metabolized?

Back 35

by CYP3A4
is strong inhibitor of

Front 36

what drug interactions should one be aware of when administering itraconazole?

Back 36

may cause fatal arrhythmias when given w/ cisapride or quinidine

Front 37

what are the PK of itrazonazole?

Back 37

poor bioavailability
poorly penetrates CSF
absorption reduced by antacids

Front 38

when is itraconazole used?

Back 38

blastomyces, sporothrix, histoplasma
effective against apsergillus
dermatophytoses and onychomycosis

Front 39

when is voriconazole used?

Back 39

blastomyces, sporothrix, histoplasma
effective against apsergillus
dermatophytoses and onychomycosis

Front 40

which is more effective against aspergillus - itraconazole or voriconaole?

Back 40

voriconazole

Front 41

what is voriconazole not effective against?

Back 41

zygomycetes

Front 42

what is the treatment of choice for invasive aspergillosis?

Back 42

voriconazole

Front 43

what are adverse effects of voriconazole?

Back 43

visual distrubances

Front 44

how is voriconazole metabolized?

Back 44

by CYP2C19
inhibits CYP2C9 and CYP3A4

Front 45

what is posazonazole active against?

Back 45

blastomyces, sporothrix, histoplasma
effective against apsergillus
dermatophytoses and onychomycosis

ZYGOMYCETES - Mucor

Front 46

how is fluconazole eliminated?

Back 46

renal

Front 47

which systemic azole penetrates the CNS?

Back 47

fluconazole

Front 48

what are the echinocandins active against?

Back 48

candida, aspergillus

Front 49

how are the echinocandins administered?

Back 49

IV

Front 50

what is the moa of the echinocandins?

Back 50

inhibit fungal cell wall synthesis

Front 51

what are the systemic antifungals used for superficial mycoses?

Back 51

griseofulvin
terbinafine
ketoconazole
fluconazole
itraconazole

Front 52

when is griseofulvin used?

Back 52

only dermatophytosis

Front 53

how is absoprtion of griseofulvin improved?

Back 53

when given w/ fatty foods

Front 54

what is the moa of griseofulvin?

Back 54

disrupts mitotic spindle and inhibits mitosis

Front 55

what is the moa of terbinafine?

Back 55

inhibits squalene epoxidase --> --> inhibition of ergosterol synthesis

Front 56

what are the adverse effects of terbinafine?

Back 56

gi upset
rash
headache
taste disturbances

Front 57

what are the topical antifungals?

Back 57

nystatin
clotrimazole
miconazole
ketoconazole
terbinafine
naftifine
butenafine
amphotericin B

Front 58

what is nystatin?

Back 58

a polyene antibiotic

Front 59

when is topical amphotericin b used?

Back 59

for cutaneous candidiasis

Front 60

what are the two most commonly used topical azoles used?

Back 60

clotrimazole and miconazole

Front 61

what is topical terbinafine effective against?

Back 61

tinea cruis and tinea corporis

Front 62

what is topical naftifine effective against?

Back 62

tinea cruis and tinea corporis

Front 63

what is butenafine?

Back 63

a benzylamine

Front 64

when is topical butenafine used?

Back 64

dermatophytes

Front 65

what is tonaftate used for?

Back 65

topically against dermatophyte

Front 66

how is pneumocystis jirovecii treated?

Back 66

co-trimoxazole (trimehoprim plus sulfamethoxazole

Front 67

what are some alternate therapies to p jirovecii?

Back 67

pentamidine
trimethoprim plus dapsone
primaquine plus clindamycin
atovaquone