Anti-fungal Agents

Question 1

Patients that are a higher risk of developing a nosocomial systemic mycoses

Answer 1

Surgical and intensive care; prosthetics; immunosuppressed

Question 2

What is the primary target in anti-fungal drugs?

Answer 2

Ergosterol biosynthesis

Question 3

Squalene is converted to lanosterol by

Answer 3

squalene epoxidase

Question 4

Lanosterol is converted to ergosterol by

Answer 4

14-alpha-sterol demethylase

Question 5

Allylamines block which enzyme?

Answer 5

Squalene epoxidase

Question 6

Azoles inhibit which enzyme

Answer 6

14-alpha-sterol demethylase

Question 7

What does a fungal cell wall contain?

Answer 7

Chitin, Beta-D-glucans, glycoproteins

Question 8

What is the structure of amphotericin B?

Answer 8

Amphoteric polyene macrolide

Question 9

How does the structure of amphotericin affect its PKs?

Answer 9

low solubility and poor oral absorption

Question 10

How does the MOA of amphotericin affect the fungal pathogens?

Answer 10

Binds to ergosterol and disrupts the membrane stability by forming pores

Question 11

When is amphotericin used?

Answer 11

life-threatening mycoses due to toxicity

Question 12

What are the toxic effects of amphotericin?

Answer 12

Cytokine storm; renal toxicity (renal ischemia and proximal tubular injury); hematologic toxicity (myelosuppression)

Question 13

Which anti-fungal inhibits DNA/RNA synthesis?

Answer 13

Flucytosine

Question 14

How is flucytosine selective for fungal cells?

Answer 14

Cytosine permease and cytosine deaminase aren’t expressed in mammals

Question 15

What is the end goal of flucytosine?

Answer 15

Inhibition of thymidylate synthase

Question 16

How does resistance against flucytosine develop?

Answer 16

mutations of permease and deaminase which lower the binding affinity

Question 17

Which drug is used to treat cryptococcal meningitis and systemic candidiasis?

Answer 17

Flucytosine

Question 18

in what patients is the use of flucytosine contraindicated?

Answer 18

Renal insufficiency

Question 19

The adverse affects of flucytosine include

Answer 19

hematologic and hepatotoxicity

Question 20

what is the MOA of griseofulvin?

Answer 20

Binding to tubulin which disrupts the assembly of the mitotic spindle

Question 21

When is griseofulvin commonly used?

Answer 21

Scalp ringworm in children

Question 22

Which drug inhibits squalene epoxidase?

Answer 22

Terbinafine

Question 23

What are the uses of terbinafine?

Answer 23

Ringworm (topical or oral); onychomycosis (oral)

Question 24

When is the use of terbinafine contraindicated?

Answer 24

liver disease

Question 25

Which drug inhibits 14-alpha-sterol demethylase?

Answer 25

Fluconazole

Question 26

How does the selectivity work for fluconazole?

Answer 26

greater affinity for the fungal CYPs than the hosts

Question 27

what is the superficial use of fluconazole?

Answer 27

vaginal yeast infections

Question 28

What is the drug interaction to be aware of when using fluconazole?

Answer 28

Fluconazole inhibits CYPs that metabolize other drugs = development of toxicities

Question 29

Which anti-fungal drug belongs to the cell wall inhibitors group?

Answer 29

Caspofungin

Question 30

What is the MOA of caspofungin?

Answer 30

Non-competitive inhibition of B-(1,3)-D-glucan synthase complex which disrupts cross-linking of the cell wall

Question 31

When would caspofungin be used?

Answer 31

severe systemic candidiasis or candidemia