Antifungal

Question 1

superficial mycoses

Answer 1

limited to outermost layers of skin and hair

Question 2

cutaneous mycoses

Answer 2

extend deeper into dermis and include invasive hair and nail diseases. Restricted to keratinized layers of skin, hair, and nails

Question 3

subcutaneous mycoses

Answer 3

involve dermis, subcutaneous tissue, muscle, and fascia

Question 4

systemic mycoses

Answer 4

originate primarily in lungs and may spread to other organ systems

Question 5

give two important examples of opportunistic mycoses

Answer 5

• aspergillosis - cryptococcosis

Question 6

all available antifungals target the cell membrane or cell wall except

Answer 6

• Griseofulvin
• Flucytosine

Question 7

MOA of Amphotericin B. static or cidal?

Answer 7

• interaction with sterol of fungal membrane, Ergosterol, that results in pore formation
• fungicidal

Question 8

spectrum of Amphotericin B

Answer 8

broad antifungal spectrum

Question 9

DOC: treatment of most systemic antifungal infections

Answer 9

Amphotericin B

Question 10

toxicities of Amphotericin B

Answer 10

• nephrotoxic
  
  • ​dose dependent - can lead to irreversible kidney damage
  • azotemia: BUN and serum creatinine levels are elevated
• binding to human membrane sterols does occur

Question 11

MOA of Flucytosine

Answer 11

• metabolic antagonism of fungal DNA and RNA
  
  • Flucytosine is converted to 5-fluorouracil which interferes with fungal DNA and RNA synthesis

Question 12

DOC: Cryptococcus infections

Answer 12

Flucytosine + amphotericin B

Question 13

spectrum of Flucytosine

Answer 13

• broad antifungal spectrum; less than amphotericin B

Question 14

important distribution of Flucytosine

Answer 14

enters CSF

Question 15

toxicities of Flucytosine

Answer 15

• depression of bone marrow
• may elevate ALT or AST
• renal impairment can lead to toxicity

Question 16

List the “Azoles.” Which is the prototype?

Answer 16

• Ketoconazole
• Fluconazole
• Voriconazole
• Itraconazole

Question 17

MOA of “Azoles.” Static or cidal

Answer 17

• inhibits the synthesis of ergosterol
• fungistatic

Question 18

spectrum of Ketoconazole

Answer 18

broad antifungal spectrum

Question 19

route of administration of Amphotericin B

Answer 19

IV

Question 20

route of administration of flucytosine

Answer 20

well absorbed orally

Question 21

route of administration of Ketoconazole

Answer 21

oral

Question 22

distribution of Ketoconazole

Answer 22

• widely distributed in the body, largely bound to plasma
• CNS penetration is low

Question 23

toxicity of Ketoconazole

Answer 23

• gyneocomastia
• inhibits P450 system, drug interactions

Question 24

route of administration of Fluconazole

Answer 24

oral and IV

Question 25

distribution of Fluconazole

Answer 25

**penetrates CSF - use for fungal meningitis**

Question 26

toxicity of Fluconazole

Answer 26

* less toxic than amphotericin B or flucytosine and better tolerated than ketoconazole * less drug interactions

Question 27

route of administration of Voriconazole

Answer 27

Oral and IV

Question 28

distribution of Voriconazole

Answer 28

Modest CSF penetration

Question 29

DOC: Aspergillus

Answer 29

Voriconazole + Amphotericin B

Question 30

toxicities of Voriconazole

Answer 30

* **drug interactions** * **visual impairment**: reversible

Question 31

toxicities of Itraconazole

Answer 31

potent inhibitor of CTP3A4 - drug interactions

Question 32

route of administration of Itraconazole

Answer 32

oral

Question 33

name the 3 Echinocandins. What is the prototype

Answer 33

* **Caspofungin** * Micafungin * Anidulafungin

Question 34

MOA of Echinocandins. static or cidal

Answer 34

inhibits synthesis of major fungal cell wall component **B(1,3)-D-glucan** * fungicidal

Question 35

route of administration of Caspofungin

Answer 35

IV

Question 36

toxicity of Caspofungin

Answer 36

lack of nephrotoxicity and few drug interactions = attractive treatment option

Question 37

uses of Caspofungin

Answer 37

* alternate treatement option: invasive Asperigillosis in refractory patients * esophageal candidiasis

Question 38

Name the three antifungals that are used for local/topical treatment

Answer 38

* **Griseofulvin** * Terbinafine * Nystatin

Question 39

dermatophytes

Answer 39

fungal infection that affects different parts of the body ex: tinea corporis

Question 40

MOA of Griseofulvin: static or cidal

Answer 40

* binds to microtubules and destroys mitotic spindle structure * binds to keratin and prevents infection in new skin * fungistatic

Question 41

DOC: Onychomycosis

Answer 41

Griseofulvin

Question 42

route of administration of Griseofulvin

Answer 42

only oral, not topical

Question 43

uses of Griseofulvin

Answer 43

treats dermatophytosis infections of skin, hair, and nails

Question 44

contraindications of Griseofulvin

Answer 44

* acute intermittent porphyria * hepatocellular failure

Question 45

route of administration of Terbinafine

Answer 45

oral or topical

Question 46

MOA of Terbinafine. static or cidal?

Answer 46

* interferes with sterol biosynthesis * fungicidal

Question 47

route of administration of Nystatin

Answer 47

* oral: GI candida infections * topical: other candida infections

Question 48

use of Nystatin

Answer 48

* polyene Abx * used for candidal infections

Question 49

What do Tioconazole, Clotrimazole, and Miconazole have in common

Answer 49

topical azoles used for skin and vaginal candidiasis

Question 50

Name the two polyene antifungal antibiotics

Answer 50

* amphotericin B * nystatin