Antifungal Drugs

Question 1

List the polyenes

Answer 1

Amphotericin B, Nystatin

Question 2

Polyene mechanism

Answer 2

Bind ergosterol, creating membrane holes. Fungicidal.

Question 3

Polyene spectrum

Answer 3

Broad, yeast and mold. Invasive systemic fungal infections in immunocomp. pts.

Question 4

Polyene distribution

Answer 4

Poor excretion, long half-life, liposomal form can cross BBB.

Question 5

Polyene toxicity

Answer 5

Toxic bc bind cholesterol; Nystatin-topical Candida. Amphotericin B decreases renal blood flow, nephrotoxicitiy.

Question 6

Polyene Resistance

Answer 6

Rare, decreased ergosterol in membrane

Question 7

List the azoles

Answer 7

fluconazolee, itraconazole, ketoconazole (not metronidazole)

Question 8

Azole mechanism

Answer 8

Binds fungal P-450 enzyme, block ergosterol production, accumulate precursor lanosterol, converts to toxic sterol. Fungistatic.

Question 9

Azole spectrum

Answer 9

most widely used antifungal

Question 10

Azole distribution

Answer 10

orally available with cola/acid to aid absorption (itraconazole, ketoconazole)

Question 11

Azole toxicity

Answer 11

drug-drug interactions, hepatotoxicity, neurotoxicity, altered hormone synthesis (pregnancy class C), can bind human CYP-450

Question 12

List the allylamines

Answer 12

Terbinafine (lamisil)

Question 13

Terbinafine mechanism

Answer 13

Inhibits squalene epoxidase–>toxic accumulation of squalene. Fungicidal.

Question 14

Terbinafine spectrum

Answer 14

Dermatophytes

Question 15

Terbinafine toxicity

Answer 15

Topical; drug interactions with CYP-2D6 substrates

Question 16

Terbinafine resistance

Answer 16

rare; decreased uptake, mutant binding site, efflux transporters.

Question 17

Flucytosine mechanism

Answer 17

antimetabolite selectively taken up/converted to fluorouracil in fungi; interfere with DNA/RNA synthesis. Fungistatic

Question 18

Flucytosine spectrum

Answer 18

Narrow-yeast Candida albicans, cryptococcus

Question 19

Flucytosine distribution

Answer 19

oral-good distribution, penetrates CNS

Question 20

Flucytosine toxicity

Answer 20

bone marrow suppression-monitor pt cell counts

Question 21

Flucytosine resistance

Answer 21

loss of converting enzyme or transporters; cotreat with amphtericin B to increase uptake

Question 22

Griseofulvin mechanism

Answer 22

binds microtubules inhibits spindle leading to multinucleate cells. Fungistatic

Question 23

Griseofulvin spectrum

Answer 23

dermatophytes

Question 24

Griseofulvin distribution

Answer 24

lipids increase oral absorption, long treatment (months) to allow concentration in dead keratinized layer of skin

Question 25

Griseofulvin toxicity

Answer 25

teratogenic-causes birth defects

Question 26

Griseofulvin resistance

Answer 26

change to beta-tubulin, resistance mutations likely to develop if pt stops taking oral treatment early

Question 27

List the echinocandins

Answer 27

caspofungin

Question 28

Caspofungin

Answer 28

cell wall inhibitor, blocks beta (1,3)-D-glucan polysaccharide synthesis. Fungicidal-candida, Fungistatic-aspergillus

Question 29

Caspofungin spectrum

Answer 29

candida albicans, systemic

Question 30

Caspofungin distribution

Answer 30

IV, large molecular wt. prohibits CNS penetration

Question 31

Caspofungin toxicity

Answer 31

limited; fever, hypersensitivity rash at injection site

Question 32

Caspofungin resistance

Answer 32

change in (1,3)-beta-D-glucan synthase gene