Anti-Fungals

Question 1

What cellular structure do Echinocandins target?

Answer 1

Cell wall: glucan synthesis

Question 2

What cellular structure do Polyenes and Azoles target?

Answer 2

Cell membrane: ergosterol synthesis

Question 3

What cellular structure do Flucytosines target?

Answer 3

DNA/RNA synthesis: pyrimidine analogues

Question 4

What is the mechanism of action of polyenes?

Answer 4

Bind directly to ergosterol

Question 5

What are the polyenes?

Answer 5

Amp-B

Nystatin

Question 6

How would you treat cryptococcal meningitis?

Answer 6

1. Amp-B w/ Flucytosine

2. Fluconazole

Question 7

Which azole crosses the BBB?

Answer 7

Fluconazole

Question 8

What is the mechanism of action of Allylamines?

Answer 8

Inhibit fungal squalene epoxidase –> cannot convert squalene to lanosterol
Interfere with ergosterol synthesis

Question 9

What is ergosterol?

Answer 9

Sterol that is part of the fungal bilayered cell membrane

Question 10

What are fungal cell walls comprised of?

Answer 10

90% chitin, GLUCAN, mannan

10% proteins, glycoproteins

Question 11

What do anti-fungals target?

Answer 11

Proteins
Nucleus
Cell wall, especially glucan
Cell membrane, especially ergosterol

Question 12

Effective anti-fungals typically have a _____, which leads to ______.

Answer 12

High therapeutic index / many adverse side effects

Question 13

What was the first anti-fungal and when was it approved?

Answer 13

Nystatin – 1954

Question 14

What class of anti-fungals is Terbinafine?

Answer 14

Allylamine (targets squalene epoxidase)

Question 15

What is the mechanism of action of Azoles?

Answer 15

Bind to and inhibit cytochrome p450 and 14-alpha demethylase –> cannot convert lanosterol to ergosterol

Question 16

What class of anti-fungals is Flucytosine?

Answer 16

Antimetabolite (pyrimidine analogue)

Question 17

What are side effects of Amp-B?

Answer 17

Chronic: Dose-dependent severe nephrotoxicity (decrease in GFR); may require dialysis
Acute: chills, fever, vomiting

Question 18

What OTC drug can you NOT take with azoles?

Answer 18

Antacids. Azoles are weak acids, therefore an antacid would inhibit them.

Question 19

What are the imidazoles?

Answer 19

Ketoconazole

Miconazole

Question 20

What are the triazoles?

Answer 20

Itraconazole
Fluconazole

**these drugs are newer and less toxic

Question 21

Broad spectrum
PO administration
Mostly replaced by Fluconazole

Answer 21

Ketoconazole

Question 22

Side effects of Ketoconazole

Answer 22

Gynecomastia

Hepatic failure

Question 23

Topical and vaginal suppositories

Dermatophytes

Answer 23

Miconazole

Question 24

Topical and vaginal suppositories

Answer 24

Clotrimazole

Question 25

Oral, esophageal, and vaginal candidiasis Used for Cryptococcal meningitis (after initial treatment with Amp-B and Flucytosine) Oral and IV

Answer 25

Fluconazole **only azole to cross BBB

Question 26

Broad spectrum including tinea unguium Indicated for systemic fungal infections Also for oral and esophageal candidiasis

Answer 26

Itraconazole

Question 27

Oral and IV introduced in 2002 High bioavailability Indicated for invasive Aspergillosis

Answer 27

Voriconazole

Question 28

How would you treat superficial fungal infections?

Answer 28

Terbinafine

Question 29

What is Flucytosine used for?

Answer 29

Systemic Candida and Cryptococcus neoformans infections

Question 30

What is Flucytosine not effective against?

Answer 30

Aspergillus

Question 31

What is the mechanism of action of the Echinocandins?

Answer 31

Inhibit 1,3-beta-glucan synthase | Cell wall synthesis inhibitor

Question 32

What class of anti-fungal is Caspofungin?

Answer 32

Echinocandin

Question 33

What is Caspofungin used for?

Answer 33

Invasive Amp-B resistant Aspergillosis Esophageal Candidiasis Pneumocystis pneumonia

Question 34

How would you treat Coccidioides immitis?

Answer 34

1. Flucytosine 2. Fluconazole, Ketoconazole, Itraconazole 3. Amp-B

Question 35

How would you treat Pneumocystis jiroveci?

Answer 35

TMP/SMX

Question 36

How would you treat Mucor/Rhizopus?

Answer 36

Amphotericin B **this infection has a 50% mortality rate even with early diagnosis