Antifungals

Question 1

All fungi are ____ organisms

Answer 1

eukaryotic

Question 2

2 types of fungal infections

Answer 2

systemic

superficial (cutaneous, subcutaneous)

Question 3

Fungal infections are the __ most common nosocomial infection

Answer 3

4th

Question 4

Patients at greatest risk for mycoses

Answer 4

• surgical intensive patients
• prosthetics
• immunosuppressed

Question 5

Fungi use _____ for cell membrane

Answer 5

ergosterol

Question 6

Squalene is converted to ______ by _______

Answer 6

lanosterol

squalene epoxidase

Question 7

Lanosterol is converted to _______ and catalyzed by _____

Answer 7

ergosterol

CYP450 (14a-sterol demethylase)

Question 8

Amphotericin B/nystatin MOA

Answer 8

bind ergosterol
disrupt membrane stability
- pores, leakage
500x greater affinity for ergosterol

Question 9

Amphotericin B fungistatic or fungicidal?

Answer 9

both!

depends on concentration and fungal sensitivity

Question 10

Amphotericin B use

Answer 10

• broad spectrum

- life threatening systemic mycoses

Question 11

BBW amphotericin B

Answer 11

for proper use

Question 12

Nystatin

Answer 12

swish and swallow

oral thrush

Question 13

Adverse reactions of amp b/nystatin

Answer 13

• infusion related effects (cytokine storm)
• renal toxicity (proximal tube)
• hematologic toxicity (myelosuppression in anemia –> decreased erythropoietin secretion)

Question 14

cytokine storm

Answer 14

fever
chills
rigors
hypotension

** pretreat with APAP

Question 15

Flucytosine MOA

Answer 15

• Transported into fungal cells by cytosine permeate
• Converted to 5FU by cytosine deaminase
• 5FU converted to 5FdUMP and FUTP

Question 16

Flucytosine fungistatic or fungicidal?

Answer 16

fungistatic

Question 17

Flucytosine resistance

Answer 17

during mono therapy, so restricted use

- due to mutations of permeate and deaminase

Question 18

Flucytosine use

Answer 18

• cryptococcal pneumonia and meningitis

- systemic candidiasis

Question 19

What drug is usually administered in combo with Amp B?

Answer 19

flucytosine

- synergistic

Question 20

BBW flucytosine

Answer 20

for dose reduction in patients with renal insufficiency

Question 21

Flucytosine adverse reactions

Answer 21

• hematologic (BM suppression)

- hepatotoxicity

Question 22

DDI between flucytosine and Amp B

Answer 22

• Amp B kidney damage, may suppress flucytosine excretion

- drugs that cause hematological toxicities

Question 23

Griseofulvin MOA

Answer 23

• mitosis inhibitor
• binds tubulin
• drug accumulates in keratin precursor and binds tightly to keratin

Question 24

Griseofulvin fungistatic or fungicidal?

Answer 24

fungistatic

Question 25

Griseofulvin use

Answer 25

- oral, dermatophytic infections of hair, skin, nails - ringworm - may take 6 months of treatment!

Question 26

Griseofulvin adverse reaction

Answer 26

- headache in children - acute intermittent porphyria - photosensitive

Question 27

Terbinafine MOA

Answer 27

inhibit squalene epoxidase

Question 28

Terbinafine fungistatic or fungicidal?

Answer 28

fungicidal

Question 29

Terbinafine use

Answer 29

- ringworm - onychomycosis (cannot penetrate into cuticle) - takes 3 months

Question 30

Terbinafine adverse reactions

Answer 30

- well tolerated topically - skin reaction - dysgeusia - heapatotoxicity

Question 31

DDI terbinafine

Answer 31

- inhibit CYP2D6, induces 3A4

Question 32

Fluconazole MOA

Answer 32

inhibit 14a sterol demtheylase

Question 33

Fluconazole fungistatic or fungicidal?

Answer 33

fungistatic

Question 34

Fluconazole triazole or imidazole?

Answer 34

triazole

Question 35

Triazoles or imidazole more selective for fungal CYP?

Answer 35

triazole

Question 36

Generalization of all 14a sterol demethylase inhibitors

Answer 36

- important difference in anti fungal spectrum, PK and side effects - check susceptibility of organism - all equally effective against candida - oral BA varies

Question 37

Fluconazole use

Answer 37

- crytpcoccal meningitis | - superficial mycoses

Question 38

Fluconazole adverse reaction

Answer 38

- generally well tolerated - GI upset - hepatoxocitiy - NO pregnancy

Question 39

DDI fluconazole

Answer 39

- inhibit CYPS

Question 40

Caspofungin MOA

Answer 40

- non-competitive inhibitors of B1,3 D gluten synthesis

Question 41

Caspofungin fungistatic or fungicidal?

Answer 41

fungicidal

Question 42

Caspofungin use

Answer 42

- aspergillosis - febrile neutropenia - severe candidiasis

Question 43

caspofungin adverse reactions

Answer 43

Almost none

Question 44

Which drugs are fungistatic?

Answer 44

Fluconazole Griseofulvin Flucytosine Amp B

Question 45

Which drugs are fungicidal?

Answer 45

Terbinafine Caspofungin Amp B