Antifungals

Question 1

What are the five classes of antifungals?

Answer 1

1) Polyenes
2) Flucytosine
3) Azoles
4) Echinocandins
5) Allylamine

Question 2

What are the two Polyenes?

Answer 2

Amphotericin B and Nystatin

Question 3

What are the two drug categories for Azoles?

Answer 3

Imidazoles and Triazoles

Question 4

What drugs are Imidazoles?

Answer 4

1) Ketonconazole
2) Miconazole
3) Clotrimazole

Question 5

What drugs are Triazoles?

Answer 5

1) Itraconazole
2) Fluconazole
3) Voriconazole
4) Posaconazole
5) Isavuconazole

Question 6

What differentiates Triazoles from Imidazoles?

Answer 6

Triazoles have two nitrogens in their azole ring while imidazoles only have one nitrogen in their azole ring

Question 7

What drug is an allylamine?

Answer 7

Terbinafine

Question 8

What is the activity of the Polyenes?

Answer 8

Broad, fungicidal, and they are active in yeast infections

Question 9

What is the activity of Flucytosine?

Answer 9

Narrow and fungistatic

Question 10

What is the activity of the Azoles?

Answer 10

Broad and fungistatic

Question 11

What is the activity of the Echinocandins?

Answer 11

Broad, fungicidal, and active against fungal and yeast infections

Question 12

What is the activity of the drug Griseofulvin?

Answer 12

Narrow and fungistatic

Question 13

What is the activity of the Allylamines?

Answer 13

Fungicidal against dermatophytes and fungistatic against yeast infections

Question 14

How do Amphotericin B and Nystatin work against infections?

Answer 14

They bind to ergosterol in the fungal cell membrane forming pores, known as death rings, which disrupts cell membrane permeability and kills the cell

Question 15

Why is resistance to the Polyenes rare?

Answer 15

Ergosterol is essential to certain functions in the fungal cell; therefore, if the cell modifies ergosterol, it could hurt its ability to function and launch infections

Question 16

If a fungal infection were to try and become resistant to the polyenes, how would it do so?

Answer 16

It decreases the concentration of ergosterol or changes its structure to decrease affinity (target modification)

Question 17

What is the most prominent toxicity associated with Amphotericin B?

Answer 17

Dose-dependent nephrotoxicity

Question 18

What are the routes of administration for Nystatin?

Answer 18

Oral and topically because it is too toxic for parenteral use

Question 19

Why is Amphotericin B less toxic than Nystatin?

Answer 19

Because Amphotericin B has a higher affinity for ergosterol rather than cholesterol and it is more selective

Question 20

Mechanism of action for 5-FC (Flucytosine)

Answer 20

5-FC is converted to 5-FU by cytosine deaminase. 5-FU is then converted to F-dUMP and F-UTP. F-dUMP inhibits DNA synthesis and F-UTP inhibits RNA synthesis.

Question 21

Mechanism of resistance to 5-FC

Answer 21

Altered metabolism of 5-FC which happens faster in monotherapy

Question 22

Toxicity to 5-FC

Answer 22

Occurs when 5-FC is converted to toxic 5-FU by intestinal microflora. Can cause Thrombocytopenia, Leukopenia, Anemia, and Bone marrow toxicity

Question 23

In regards to Polyenes, which one is stronger with less toxicity and why?

Answer 23

Amphotericin B because it has more double bonds than Nystatin

Question 24

What happens when Polyenes interact with UV light?

Answer 24

Their double bonds become locked in the cis position and they are inactivated

Question 25

What is 5-FC combined with to create a synergistic reaction?

Answer 25

Azoles and Amphotericin B because they compromise the cell membrane and increase intracellular concentrations of 5-FC

Question 26

Mechanism of action for Azoles

Answer 26

They inhibit the biosynthesis of ergosterol by inhibiting the p450 14alpha-demethylase enzyme

Question 27

Mechanism of resistance to Azoles

Answer 27

Altered p450 14alpha-demethylase enzyme and active efflux

Question 28

Toxicity associated with Azoles

Answer 28

GI upset, liver enzyme abnormalities, rarely but sometimes hepatitis, and they all inhibit cytochrome p450 (especially CYP3A4)

Question 29

Which types of Azoles are more effective and less toxic?

Answer 29

Triazoles because they are more selective

Question 30

Which imidazole is a more potent inhibitor of human cyt. p450 meaning it is less selective and causes more adverse effects?

Answer 30

Ketoconazole

Question 31

What has the widest therapeutic index of all the Azoles?

Answer 31

Fluconazole

Question 32

What three drugs are Echinocandins?

Answer 32

Caspofungin, Micafungin, and Anidulafungin

Question 33

Mechanism of action for Echinocandins

Answer 33

They inhibit the biosynthesis of the fungal cell wall by inhibiting Beta(1, 3)-glucan synthase

Question 34

Mechanism of action for Griseofulvin

Answer 34

Not clearly understood but it binds to and protects newly formed keratin from fungal infection

Question 35

Toxicity of Griseofulvin

Answer 35

Inducer of cytochrome p450

Question 36

What is the route of administration for Griseofulvin?

Answer 36

Oral to treat systemic infections caused by dermatophytes

Question 37

Mechanism of action for Terbinafine

Answer 37

Inhibits the biosynthesis of ergosterol by inhibiting the squalene epoxidase enzyme. This also leads to an accumulation of sterol squalene which is toxic to fungal cells

Question 38

Toxicity for Terbinafine

Answer 38

Gi upset and headache. Inhibitor of cytochrome p450 2D6 enzyme