53: Antifungal Chemotherapy

Question 1

drug of choice aspergillosis

Answer 1

voriconazole

Question 2

drug of choice mild to moderate blastomycosis

Answer 2

itraconazole

Question 3

drug of choice moderate to sever blastomycosis

Answer 3

amphotericin followed by itraconazole

Question 4

drug of choice vaginal candidiasis

Answer 4

intravaginal azole (clotrimazole, miconazole) OR intravaginal nystatin OR fluconazole (oral)

Question 5

drug of choice oropharyngeal candidiasis

Answer 5

clotrimazole ro miconazole lozanges O”r nystatin oral suspension OR fluconazole

Question 6

drug of choice esophageal candidiasis

Answer 6

fluconazoe

Question 7

drug of choice invasive or blood stream candidiasis

Answer 7

fluconazole or echinocandin

Question 8

drug of choice coccidiomycosis

Answer 8

fuconazole ro itraconazole

Question 9

drug of choice cryptococcosis

Answer 9

amp B plus flucytosine followed by fluconazole

Question 10

drug of choice cryptococcosis suppression in HIV pts

Answer 10

fluconazole

Question 11

drug of choice histoplasmosis

Answer 11

ammphB followed by itraconazole

Question 12

drug of choice histoplasmosis suppression in HIV pts

Answer 12

itraconazole

Question 13

drug of choice murcomycosis

Answer 13

amp B

Question 14

drug of choice cutaneous sporotrichosis

Answer 14

itraconazole

Question 15

drug of choice extracutaneous sporotrichosis

Answer 15

ampB followed by itraconazole

Question 16

drug of choice dermatomycosis

Answer 16

topical azole (clotrimazole, micronazole) or topical terbinafine

Question 17

drug of choice onychomycosis

Answer 17

terbinafine (oral) or itraconazole (oral)

Question 18

MOA amphotericin B

Answer 18

binds to ergosterol in fungal cell membrane

forms amp b containing pores –> alter membrane permeability

fungicidal

Question 19

most common and most serious long-term toxicity of amp B

Answer 19

nephrotoxicity

also see infusion related general reactions in nearly all patients

Question 20

liposomal packaged formulations of amp B are _______-

Answer 20

less toxic

formulations result in less interaction of drug with mammalian cell membranes –> decreases toxicity

Question 21

azoles w 2N v. 3N

Answer 21

imiadazoles

triazoles

Question 22

MOA azoles

Answer 22

bind to enzyme responsible for converting lanosterol to ergosterol

reduction of ergosterol in fungal cell membrane results in damaged and leaky cell membranes

Question 23

how do fungi become resistant to azoles?

Answer 23

• efflux pumps
• mutations in the target enzyme
• decreased ergosterol content in cell membrane

Question 24

highest therapeutic index of all azoles

Answer 24

fluconazole

also lowest level of interaction with p450s of all azoles

Question 25

agent of choice in treating candidiasis, cryptococcis, and coccidiomycosis?

Answer 25

fulconazole

second line agent for other systemic infections including hisoplasmosis, blastomycosis, and sporotrichosis

Question 26

_______ broader spectrum of activity than fluconazole but poorer pharmacology and therapeutic index

Answer 26

itraconazole

Question 27

special precautions for itraconazole

Answer 27

requires low gastric H for absorptions (impaired by antacids, PPIs and H2 blockers)

penetration to the CSF is absent

Question 28

drug of choice for treating blastomycosis, cocidiomycosis, histoplasmosis, sporotrichosis, and onychomycosis?

Answer 28

itraconazole

Question 29

*treatment of choice for aspergillosis

Answer 29

voriconazole

Question 30

adverse voriconazole

Answer 30

transient visual distrubances, hallucinations, blurred vision, altered perception of collor

*liver enzyme abnormalities and rash are common

Question 31

_______ broadest spectrum of activity of all azoles

Answer 31

posaconazole

demonstrated effectivenss in treating most species of candida, aspergillus and agents of mucormycoses

Question 32

how is flucytosine, an anti-neoplastic agent, used in antifungal applications?

Answer 32

used as part of a combination therapy for some systemic infections

*combo therapy in cryptococal infection (into the CNS)

Question 33

MOA flucytosine

Answer 33

transported by cytosine permease into the fungal cell where is it converted to 5FU and incorporated into RNA - messing stuff up, etc.

Question 34

adverse reactions flucytosine

Answer 34

bone marrow toxicity

Question 35

MOA echinocandins

Answer 35

inhibit synthesis of beta-glucans (essential component of fungal cell walls not found in mammalian cells)

Question 36

use for echinocandins

Answer 36

invasive infections caused by candida and aspergillus – $$ if others don’t work

Question 37

oral systemic drugs for cutaneous and mucocutaneous infections

Answer 37

griseofulvin

terbinafine

Question 38

second-line oral agent used in treatment of dermatophyte infections

Answer 38

griseofulvin

concentrates in keratin precursor cells

Question 39

drug interactions for griseofulvin

Answer 39

increases warfarin metabolism and decreases effectiveness of oral contraceptives

Question 40

MOA allylamines (terbinafine, naftifine)

Answer 40

inhibit squalene epoxidase to stop ergosterol synthesis

Question 41

first line drug in treatment of onychomycosis

Answer 41

oral terbinafine

keratophilic concentrating in skin, hair, and nails

Question 42

topical antifungal agents

Answer 42

nystatin
clotirimazle
miconazole
terbinafine
naftifine

Question 43

treatment for candida cystis

Answer 43

oral fluconazole

Question 44

septae hyphae br= anching at 45 degree angle

Answer 44

aspergillosis

Question 45

treatment of choice for invasive aspergillosis

Answer 45

voriconazole