Antifungals

Question 1

Cause of increased incidence and severity of fungal infections

Answer 1

1. surgery in deeper parts of the body
2. nonspecific cancer treatment knocking out immune system
3. intubation
4. increased use of broad-spectrum antibiotics
5. HIV -> immunocompromised

Question 2

Usual fungal infection location

Answer 2

skin and mucous membranes, local or superficial mycosis

Question 3

infection with pneumonia which spreads to heart, lungs, brain, kidneys via bloodstream

Answer 3

Invasive Aspergillosis

Question 4

deep fungal infection that may affect the brain, orbit and cheekbones

Answer 4

Mucomycosis

Question 5

Ideal Antifungal Properties

Answer 5

1. selectively eliminates funal pathogens from a host with minimal toxicity
2. fungistatic/cidal
3. affects funal cell wall/membrane

Question 6

Antifungal classification due to use

Answer 6

Systemic: systemic infections

Oral or Topical: mucocutaneous

Question 7

Antifungal classification due to chemical structure

Answer 7

Polyenes
Azoles (imidazoles, triazoles)
Anti-metabolites
Allylamines
Echinocandins
Morpholines

Question 8

Polyene MOA

Answer 8

interacts with sterols in cell membrane, forming channels through which small molecules and ions leak from the inside to outside of fungal cell; FUNGICIDAL

Question 9

Sterol in fungal cell wall

Answer 9

ergosterol

Question 10

Polyene examples

Answer 10

Amphotericin B
Nystatin
Natamycin

Question 11

Azole MOA

Answer 11

inhibit cytochrome P450-dependent enzymes (C14-demethylase) involved in biosynthesis of ergosterol

Question 12

most common type of anti-fungal in practice

Answer 12

Azole

Question 13

Azole examples

Answer 13

Fluconazole
Itraconazole
Ketoconazole

Question 14

Azole general clincial use

Answer 14

for systemic fungi (dermatophytes)
fungistatic
broad spectrum

Question 15

resistance to azole may develop by

Answer 15

• alteration of demethylase

- enhanced removal from the fungal cell

Question 16

most common adverse effect of azoles

Answer 16

gastrointestinal upset (minor)

Question 17

(imid)azole prototype

Answer 17

Ketoconazole

Question 18

Ketoconazole mode of administration

Answer 18

orally

topically (mainly)

Question 19

prereq of Ketoconazole to effect

Answer 19

acidic environment; doesn’t enter CNS well

Question 20

how is Ketoconazole distinguished from Triazoles

Answer 20

greater propensity to inhibit mammalian cytochrome p450; less selective for fungal P450

Question 21

more currently used for system fungal infections

Answer 21

triazoles

• fluconazole
• itraconazole

Question 22

T/F fluconazole is not metabolized

Answer 22

T; excreted unchanged

Question 23

Fluconazole is mainly used for treatment of ______

Answer 23

mucocutaneous candidiasis

Question 24

Itraconazole is the choice of treatment for diseases due to:

Answer 24

1. dimorphic fungi histoplasma
2. Blastomyces
3. sporothrix
   dermatophytoses, onychomycosis

Question 25

Azole of choice for Blastomycoses

Answer 25

Itraconazole

Question 26

Itraconazole modes of administration

Answer 26

oral and IV

Question 27

important drug interaction with itraconazole

Answer 27

Rifampicin! reduces bioavailablity of itraconazole

Question 28

azole of choice for aspergillosis and mode of administrations

Answer 28

Voriconazole

IV, orally

Question 29

azole used for invasive candidiasis, aspegillosis and Zygomycetes

Answer 29

Posaconazole

Question 30

T/F Posaconazole can be given IV

Answer 30

F; only oral available

Question 31

Drug interaction possibility of Posaconazole

Answer 31

Inhibits CYP3A4

Question 32

Example of Anti-metabolite

Answer 32

Flucytosine (5-FC)