Antifungals

Question 1

Which two opportunistic fungal infections will be molds in the body?

Answer 1

Aspergillosis and Mucormycosis (there are no butterflies in either Sketch)

Question 2

Although Aspergillus is found predominately in immunocompromised people, it is not found in those with HIV. Why?

Answer 2

Neutrophils can kill Aspergillus, so typically it occurs in people who are granulocytopenic.

Question 3

Describe the structure of the fungal cell wall from outside to inside.

Answer 3

Outer surface 
• Mannoproteins
•Beta-1,3-glucan 
•Chitin
•Phospholipid bilayer with ergosterol
Inner surface

Question 4

The name amphotericin can help you remember its chemical properties: _______________.

Answer 4

it is amphipathic, with a nonpolar and polar section

Question 5

How exactly does amphotericin work?

Answer 5

It binds to the hydrophobic portion of ergosterol and then the hydrophilic portion of amphotericin makes a pore that destroys the membrane gradient.

Question 6

Why can’t amphotericin be orally absorbed?

Answer 6

It has a large hydrophobic region and will not dissolve well.

Question 7

Amphotericin can be administered two ways: ________________.

Answer 7

intravenously or intrathecally

Question 8

Patients are often premedicated with _______________ to eliminate the adverse infusion reactions.

Answer 8

acetaminophen or hydrocortisone

Question 9

Although amphotericin is occasionally used for ____________, there are newer drugs that are more effective.

Answer 9

Candida

Question 10

True or false: amphotericin works synergistically with the azoles.

Answer 10

False. Azoles inhibit the synthesis of ergosterol and amphotericin relies on ergosterol to be fungicidal, so it wouldn’t make sense to co-administer them.

Question 11

The newer azoles are of the _____________ type.

Answer 11

triazole

Question 12

How do fungi become resistant to the azoles?

Answer 12

They can develop efflux pumps or point mutations in CYP.

Think of a bike pump on the road to Oz.

Question 13

The azoles are good for _____________ because they are orally available.

Answer 13

outpatient treatment

Question 14

Which azole can reach the CSF?

Answer 14

Fluconazole (like the flying monkey with the helmet)

Question 15

Ketoconazole has what two side effects?

Answer 15

Gynecomastia and GI upset

Question 16

Fluconazole has what side effects?

Answer 16

GI upset, teratogen, and drug interactions

Question 17

How is fluconazole metabolized?

Answer 17

Renally (with a long half-life of 25 hours)

Note: all other azoles are hepatically metabolized.

Question 18

Voriconazole has what unique side effects?

Answer 18

Visual changes: loss of color vision; flashes of light

Question 19

______________ are now used as empiric therapy for fungal septicemia in the immunosuppressed.

Answer 19

The echinocandins

Question 20

The echinocandins must be given _________________.

Answer 20

intravenously

Question 21

The dose of echinocandins must be altered in those with _____________ insufficiency.

Answer 21

hepatic

Question 22

Echinocandins cause what side effects?

Answer 22

GI upset, skin rashes, and headache (relatively safe overall)

Question 23

What antifungal is given as a prodrug that requires intracellular activation?

Answer 23

Flucytosine, which must be activated by cytosine deaminase

Question 24

How is flucytosine administered?

Answer 24

Orally

Question 25

______________, in addition to fluconazole, also distributes to the CSF.

Answer 25

Flucytosine

Just remember that the FLUs FLY to the CSF.

Question 26

True or false: amphotericin B is commonly given to pregnant women.

Answer 26

True! It’s one of the only antifungals shown to be safe in pregnancy.

Question 27

Describe the distribution of griseofulvin.

Answer 27

It is not absorbed well orally because it requires lots of fat, but because it accumulates in keratin-containing tissues it can be given orally for skin and nail infections.

Question 28

What are the side effects of griseofulvin?

Answer 28

Headache and CYP induction

Question 29

Which antifungals are fungicidal and fungistatic?

Answer 29

•Fungicidal:

• Amphotericin
• Terbinafine
• Echinocandins
• Nystatin

•Fungistatic:

• Griseofulvin
• Azoles

Flucytosine –not stated in the handout

Question 30

Amphotericin must be dose-limited in patients with _____________.

Answer 30

renal impairment

Question 31

True or false: IV nystatin can treat esophageal candidiasis.

Answer 31

False. Because of its toxicity, nystatin is limited to topical and oral treatment. It is poorly absorbed, so oral use does not lead to toxicity.

Question 32

Sketchy left an important side effect out of the azoles scene: ________________.

Answer 32

they are teratogens

Question 33

The echinocandins cannot be used to treat ______________.

Answer 33

CSF infections

Question 34

Which is absorbed better, terbinafine or griseofulvin?

Answer 34

Terbinafine

Question 35

Newer azoles can be used for ______________.

Answer 35

mucormycosis