Anti-Fungals

Question 1

Systemic Fungi (4)

Answer 1

Histoplasma
Blastomyces
Coccidioides
Sporothrix

Question 2

Opportunistic (3)

Answer 2

Candida
Aspergillus
Cryptococcus - india ink stain

Question 3

Cutaneous/Subcutaneous (2)

Answer 3

Sporthrix

Dermatophytes - ringworm, athletes foot, onychomycosis

Question 4

Unique Targets of Fungi

Answer 4

Fungal cell membrane - ERGOSTEROL

Fungal cell wall - GLUCANS

Question 5

Shared targets of humans and fungi

Answer 5

DNA/RNA Synthesis

Cell division

Question 6

Systemically Active Drugs

Answer 6

Polyenes - AMPHO B
Azoles - most of them
FLUCYTOSINE
ECHINOCANDINS

Question 7

Amphotericin B MOA

Answer 7

BINDS ERGOSTEROL - can also bind cholesterol (toxicity)

Forms PORES - alters membrane permeability

poor CNS penetration, but otherwise widely distributed

Question 8

Amphotericin B resistance

Answer 8

REDUCED ERGOSTEROL LEVELS - reduces affinity for ampho B

Question 9

Amphotericin B adverse reactions

Answer 9

infusion related - fever, chills, muscle spasms, vomiting, headache, HTN

NEPHROTOXICITY

Question 10

Mechanism used to decrease ampho B toxicity?

Answer 10

LIPOSOMAL PACKAGED - reduces non-specific binding to human cell membranes

Question 11

Azoles MOA

Answer 11

bind enzyme responsible for CONVERTING LANOSTEROL TO ERGOSTEROL

causes leaky, damaged cell membranes to form

Question 12

Imidazoles (3)

Answer 12

ketoconazole
miconazole
clotrimazole

Question 13

Triazoles (4)

Answer 13

fluconazole
itraconazole
voriconazole
posaconazole

Question 14

Resistance to Azoles

Answer 14

EFFLUX PUMPS
target enzyme mutations
decreased ergosterol content

Question 15

Ketoconazole drastically inhibits what?

Answer 15

CYTOCHROME P450

Question 16

What azole has widest therapeutic index?

Answer 16

FLUCONAZOLE

90% absorption from GI tract
widely distributed
water soluble

Question 17

Itraconazole vs Fluconazole

Answer 17

itraconazole has BROADER SPECTRUM OF ACTIVITY

POORER THERAPEUTIC INDEX

Question 18

Voriconazole treatment of choice for?

Also an inhibitor of what?

Answer 18

ASPERGILLOSIS - decreased toxicity to ampho B

cytochrome P450

Question 19

Posaconazole has what?

Answer 19

BROADEST SPECTRUM OF ACTIVITY

Question 20

Flucytosine never used?

typically used for?

Answer 20

by itself

SEVERE CRYPTOCOCCAL MENINGITIS

Question 21

Flucytosine adverse reaction?

Answer 21

BONE MARROW TOXICITY

Question 22

Echinocandins MOA

3 drugs

Answer 22

LIPOPEPTIDES - INHIBIT SYNTHESIS OF BETA-GLUCANS (essential component of most fungal cell walls)

caspofungin
micafungin
anidulafungin

Question 23

Echinocandins work well against (2)?

Answer 23

Candida

Aspergillus

Question 24

Drugs administered orally but for skin infection?

Answer 24

Griseofulvin

Allylamines - terbinafine

Question 25

Griseofulvin used for?

Concentrates in?

Answer 25

DERMATOPHYTE INFECTIONS

Keratin pre-cursor cells

Question 26

Terbinafine (allylamine) MOA

First line tx for?

Answer 26

INHIBIT SQUALENE EPOXIDASE

ONYCHOMYCOSIS

Question 27

Topical Antifungals (3)

Answer 27

Polyenes - nystatin

Azoles - clotrimazole, miconazole

Allylamines - terbinafine, naftifine

Question 28

Nystatin most commonly used for?

Answer 28

local infections

oropharyngeal and vaginal candidiasis