Exam 8: Antifungal Agents

Question 1

What are 5 drugs used for systemic mycosis?

Answer 1

Amphoteracin B
Ketoconazole
Miconazole
Fluconazole
Itraconazole

Question 2

When is empiric anti fungal therapy used? What are two drugs that are used?

Answer 2

In seriously ill, neutropenic patients.

Amphoteracin B or Miconazole

Question 3

What are drugs used to treat Candidiasis?

Answer 3

Amphoteracin B
-Azoles
Nystatin
Terbinafine

Question 4

What are 4 mechanisms of anti fungal drugs?

Answer 4

1. Affect Membrane function (amphoteracin B)
2. Affect Cell wall synthesis
3. Affect Ergosterol synthesis
4. Affect nuclear division (Griseofulvin)

Question 5

describe the synthesis of Ergosterol

Answer 5

Squalene is converted to Lanosterol by Squalene monooxygenase
lanosterol is converted to ergosterol by c14 alpha demethylase (p450)

Question 6

Amphoteracin B formulation challenge

Answer 6

It is insoluble, but i administered parenterally somehow

Question 7

What is the mechanism of amphoteracin B?

Answer 7

Affects membrane function

Binds to ergosterol in the cell membrane, which causes pores to form and loss of membrane integrity.

Question 8

What are 2 adverse effects of Amphoteracin B?

Answer 8

1. Can also interact with human sterols, causing nephrotoxicity
2. It can cause anemia by decreasing erythropoietin production
   These are both due to affects of sterols in the kidney

Question 9

What are two non fungal infections that are treated with amphoteracin?

Answer 9

Leishmaniasis
Amebic meningoencephalitis (Naegleria fowler)

Question 10

What are two types of -azoles? Which has a longer half life?

Answer 10

Imidazoles (2 nitrogens in the ring)
Triazoles (3 nitrogens in the ring)
Triazoles have a longer half-life

Question 11

What are two triconazoles?

Answer 11

Itraconazole
Fluconazole
they have a longer half life (easier dosing)

Question 12

What is the mechanism of -azoles?

Answer 12

Inhibition of 14 alpha demethylase that converts Lanosterol to Ergosterol
Disrupts the cell membrane

Question 13

What are adverse effects of Ketoconazole?

Answer 13

Endocrine abnormalities (decreased androgen production)
They shut down steroid synthesis
they also inhibit p450 enzymes

Question 14

How is fluconazole dosed?

Answer 14

once per day due to a pretty long half life

Question 15

Griseofulvin mehcnaism

Answer 15

Disrupts mitotic spindle structure, arresting the cell in metaphase

Question 16

how fast does griseofulvin work?

Answer 16

slowly, take weeks to months to work.

Question 17

What is the mechanism of Nystatin?

Answer 17

Binds to sterols in the cell membrane (similar to amphoteracin B)
Disrupts cell membrane

Question 18

How is nystatin used?

Answer 18

Topically, orally

Too toxic for parental use (as opposed to amphoteracin B)

Question 19

Tolnaftate, Terbinafine mechanism

Answer 19

Inhibits squalene monooxygenase, inhibiting of Lanosterol…Ergosterol.

Question 20

Caspofugin Mechanism

Answer 20

Inhibits B 1,3 glucansynthase (synthesis of glucans)

Question 21

What is the use of Caspofugin?

Answer 21

Invasive cases of aspergillosis and esophageal candidiasis in patients who are refractory to other anti fungals
*** This is going to be on the test

Question 22

What is the only specific use we have to know when it comes to anti fungals?

Answer 22

Caspofugin’s