Antifungals

Question 1

2 groups of fungal infections

Answer 1

Systemic
Superficial

Question 2

What do fungi use to maintain plasma membrane structure/function?

Answer 2

Ergosterol

Question 3

How is ergosterol made by fungi?

Answer 3

Squalene —> lanosterol —> ergosterol

Question 4

Fungal cell wall components

Answer 4

Chitin
B-D-glucans
Glycoproteins

Question 5

Inhibitor of fungal membrane stability

Answer 5

Amphotericin B

Question 6

Amphotericin B MOA

Answer 6

Binds ergosterol and forms pores in the membrane

Question 7

Clinical uses of Amphotericin B

Answer 7

Broad spectrum, LIFE-THREATENING systemic fungal infections
(Boxed warning for appropriate.use only)

Question 8

How should Amphotericin B be administered

Answer 8

IV infusion over 4-6 hours (cytokine storm if not given slowly)

Question 9

Amphotericin B adverse effects

Answer 9

Renal toxicity
Myelosuppression resulting in anemia (less EPO released from kidneys)

Question 10

Fungal nucleic acid synthesis inhibitor

Answer 10

Flucytosine

Question 11

Flucytosine MOA

Answer 11

Inhibits DNA/RNA synthesis
is converted to 5-FU then 5-FdUMP which inhibits thymidylate synthase

Question 12

Clinical uses of flucytosine

Answer 12

Narrow spectrum used for cryptococcal meningitis and systemic candidiasis
Used in combination with Amphotericin B

Question 13

Boxed warning for flucytosine

Answer 13

Dose reduction in patients with renal insufficiency

Question 14

Adverse reactions of flucytosine

Answer 14

Direct myelosuppression (monitor CBC)
Hepatotoxicity

Question 15

Fungal mitotic inhibitor

Answer 15

Griseofulvin

Question 16

Griseofulvin MOA

Answer 16

Binds tubulin to disrupt assembly of mitotic spindle

Question 17

Griseofulvin accumulates in ____ precursor cells to allow new growth of skin, hair, and nails to be free of fungal infection

Answer 17

Keratin

Question 18

Griseofulvin is not effective against ___ or ____

Answer 18

Candida
Systemic fungal infections

Question 19

Clinical uses of griseofulvin

Answer 19

Oral administration to treat dermatophyte infections of hair, skin and nails, including scalp ringworm

Question 20

How long does griseofulvin take to work?

Answer 20

Up to 6 months

Question 21

Griseofulvin adverse effects

Answer 21

Headaches
Photosensitivity

Question 22

Fungal squalene epoxidase inhibitor

Answer 22

Terbinafine

Question 23

Terbinafine MOA

Answer 23

Prevents conversion of squalene to lanosterol by inhibiting squalene epoxidase
Causes toxic accumulation of squalene

Question 24

Clinical uses of Terbinafine

Answer 24

Topical use for ringworm/tinea
Oral use for onychomycosis

Question 25

Adverse effects of Terbinafine

Answer 25

Dermal irritation Taste disturbance (dysgeusia) Hepatotoxicity

Question 26

Fluconazole MOA

Answer 26

Blocks conversion of lanosterol to ergosterol by inhibiting 14a-sterol demethylase

Question 27

Fluconazole clinical uses

Answer 27

Broad spectrum Cryptococcal meningitis Superficial mycoses Candida yeast infections

Question 28

Fluconazole adverse effects

Answer 28

GI upset Inhibits CYP (drug interactions) Hepatotoxicity

Question 29

When is fluconazole contraindicated?

Answer 29

Pregnancy

Question 30

Inhibitor of fungal cell wall synthesis

Answer 30

Caspofungin

Question 31

Caspofungin MOA

Answer 31

Disrupts cross-linking of cell wall causing osmotic stress and cell lysis (fungicidal)

Question 32

Clinical uses of caspofungin

Answer 32

Severe systemic candida infections Empiric therapy for persistent febrile neutropenia