Antifungals

Question 1

Are fungi prokaryotic or eukaryotic?

Answer 1

Eukaryotic

Question 2

What is a mycoses infection?

Answer 2

Fungal infection

Question 3

Main difference in the membrane of mammalian cells vs fungi cells?

Answer 3

The main sterol in the membrane is ergosterol (in fungi) rather than cholesterol

Question 4

Role of ergosterol in the fungi membrane?

Answer 4

Provides structure and rigidity

Question 5

Name two polyene drugs

Answer 5

Amphotericin and nystatin

Question 6

MOA of amphotericin?

Answer 6

Binds to ergosterol in the membrane and forms an ion channel. Allows for efflux of K and Mg which results in cell death

Question 7

Which antifungal drugs are poorly absorbed orally so commonly given by IV?

Answer 7

The Polyenes

Question 8

Why should the polyenes be given by SLOW IV infusion?

Answer 8

Because if fast, the concentration will be higher which may cause the drug to bind to cholesterol as well as ergosterol

Question 9

Name 2 classes of drugs that inhibit ergosterol synthesis

Answer 9

Allylamines and azoles

Question 10

Name an allylamine

Answer 10

Terbinafine

Question 11

Terbinafine MOA?

Answer 11

Inhibits squalene epoxidase = an enzyme in the synthesis pathway for ergosterol

Question 12

Terbinafine’s MOA has 2 main effects. What are they

Answer 12

1. Accumulation of intracellular squalene = toxic

2. Prevention of ergosterol synthesis = prevents new fungi cells from being made

Question 13

Name an imidazole

Answer 13

Miconazole

Question 14

Name a triazole

Answer 14

Fluconazole

Question 15

MOA of azole’s?

Answer 15

Prevents ergosterol synthesis by inhibiting the fungal 14-alpha-sterol demethylase enzyme

Question 16

Which antifungal drugs interact with CYP enzymes?

Answer 16

Azoles

Question 17

Active form of flucytosine?

Answer 17

5-FU = 5- fluorouracil

Question 18

MOA of 5-FU?

Answer 18

Inhibits thymidylate synthetase which inhibits DNA synthesis

Question 19

Difference between flucytosine being used as an antifungal vs cancer drug?

Answer 19

Administered as the prodrug form (flucytosine) when an antifungal. Gets converted into active form inside the fungi cell. As a cancer drug, it is administered as the 5-fu active form

Question 20

Which drug is commonly combined with amphotericin and why?

Answer 20

Flucytosine.
This is because resistance is very common and involves preventing flutocytosine from entering the cell. Amphotericin disrupts the membrane, allowing the drug to enter the cell