Antifungal agents

Question 1

What is a main target for selective therapy against fungus

Answer 1

ergosterol, which is used in membranes instead of cholesterol

Question 2

What is the nucleic acid synthesis inhibitors

Answer 2

flucytosine

Question 3

Flucytosine MOA

Answer 3

selective active transport (cytosine permease), converted to 5-FU then 5FdUMP, fungistatic

Question 4

Resistance to Flucytosine

Answer 4

must be used in combination due to development of resistance in individual patient

Question 5

Therapeutic uses of flucytosine

Answer 5

1) yeast infections
2) fungal meningitis
3) Aspergillus
w/ amphotericin B

Question 6

Adverse effects of flucytosine

Answer 6

hematologic, hepatotoxic, w/ amphotericine B can cause kidney damage, CYP3A4 inhibitor

Question 7

Mitosis inhibitor antifungal drug

Answer 7

Griseofulvin

Question 8

MOA of griseofulvin

Answer 8

interupts mitotic spindle, fungistatic. Accumulates in keratin

Question 9

Therapeutic use of griseofulvin

Answer 9

Oral, hair, skin, and nail fungal infections may take 2-6 weeks, commonly used for scalp ringworm. Replaced by faster acting drugs

Question 10

Adverse reactions to griseofulvin

Answer 10

headaches, AIP, photosensitivity

Question 11

What is AIP

Answer 11

acute intermittent porpyria, due to induction of CYPs that increase demand for heme.

Question 12

Squalene epoxidase inhibitors

Answer 12

terbinafine (lamisil)

Question 13

MOA of terminafine

Answer 13

inhibits squalene epoxidase, squalene acumulation is fungicidal

Question 14

Therapeutic uses of terminafine

Answer 14

topical for ringworm, oral use for to and fingernails

Question 15

Adverse reactions to terminafine (4)

Answer 15

inhibits CYP 2D6, induces 3A4
skin reactions
disturbance of taste
hepatotoxicity

Question 16

Azole prototype

Answer 16

fluconazole

Question 17

MOA of fluconazole

Answer 17

inhibits ergosterol formation, fungistatic (CYP mediated)

Question 18

What are the two classes of azole

Answer 18

imidazoles and triazoles, triazoles more selective

Question 19

Therapeutic use of fluconazole

Answer 19

broad spectrum, topicaly or orally

Question 20

Adverse reactions to fluconazole

Answer 20

generally well tolerated

1) GI upset
2) inhibition of CYPs
3) hepatotoxicity
4) avoid during pregnancy

Question 21

What is the “swish and swallow” treatment for thrush

Answer 21

nystatin

Question 22

Inhibitors of fungal membrane stability

Answer 22

amphotericin B, nystatin

Question 23

Amphotericin B MOA

Answer 23

binds ergosterol and disrupts membrane stability

Question 24

Therapeutic uses of amphotericin B

Answer 24

IV, for systemic life threatening fungal infections, including meningitis

Question 25

Adverse reactions to amphotericin B

Answer 25

Well-tolerated topically and orally
IV infusion can cause cytokine storm, renal toxicity, hematologic toxicity
lipid formulation less toxic, more expensive

Question 26

Inhibitors of fungal cell wall synthesis

Answer 26

caspofungin

Question 27

MOA of caspofungin

Answer 27

disrupts cell wall integrity resulting in osmotic stress and lysis, fungicidal

Question 28

Adverse effects of caspofungin

Answer 28

none, histamine w/ infusion