Antifungal Agents

Question 1

What type of drug is 5-Flucytosine

Answer 1

Fluorinated Pyrimidine Analogue

Question 2

How do Fluorinated Pyrimidine Analogues work?

Answer 2

Pose as DNA or RNA base and are mis-incorporated into the DNA or RNA of a fungus.
Cannot be transcribed or translated => vital proteins cannot be produced.

Question 3

What type of drug are Nystatin and Amphotericin B

Answer 3

Polyenes

Question 4

How do Polyenes work?

Answer 4

Bind to ergosterol (major component of the fungal cell membrane). This increases the permeability of the plasma membrane and causes oxidative damage.

Question 5

What type of drug are Terbinafine and Naftifine?

Answer 5

Allylamine

Question 6

What type of drug is Terbinafine?

Answer 6

Allylamine

Question 7

What type of drug is Tolnaftate?

Answer 7

Thiocarbamate

Question 8

How do Allylmines and Thiocarbamates work?

Answer 8

They prevent ergosterol synthesis by non-competitively inhibiting squalene epoxidase (erg1p).
Squalene epoxidase converts squalene to lanosterol (which is required for ergosterol biosynthesis).

Question 9

Will the inhibition of the squalene epoxidase (erg1p) affect humans?

Answer 9

No. They produce lanosterol via a different enzyme

Question 10

Are Allylmines and Thiocarbamates fungistatic or fungicidal?

Answer 10

Fungistatic

Question 11

Name some Triazoles

Answer 11

Fluconazole, Itraconazole

Posaconazole, Terconazole, Voriconazole

Question 12

Name some Imidazoles

Answer 12

Clotrimazole, Ketoconazole, Tioconazole

Butoconazole, Miconazole

Question 13

Are Azoles fungistatic or fungicidal?

Answer 13

Fungistatic

Question 14

How do Azoles work?

Answer 14

They inhibit the enzymes lanosterol 14a-demethylase (Erg11p) and CD-demethylase.
This leads to inhibition of ergosterol biosynthesis.

Azoles bind to the Iron of heme of the p450 enzyme.
The halogenated phenyl group of the azole fits into the hydrophobic binding pocket of the 17-alkyl chain of the endogenous steroid substrate.
A pi-pi stacking interaction may occur, between this halogenated phenyl group and the aromatic tyrosine residue (132) of the enzyme.

Question 15

How do Azoles work?

Answer 15

They inhibit the enzymes lanosterol 14a-demethylase (Erg11p) and CD-demethylase.
This leads to inhibition of ergosterol biosynthesis.

Question 16

What type of drug are Caspofungin, Micofungin and Anidulofungin?

Answer 16

Echinocandins

Question 17

How do Echinocandins work?

Answer 17

They inhibit 1,3-B-D-glucan synthase (Fks1/2p).
This leads to inhibition of fungal cell wall biosynthesis, as fungal cell walls are made from sugars, specifically 1,3-B-D-glucans.

Question 18

Are Azoles fungistatic or fungicidal?

Answer 18

Fungistatic

Question 19

Are Echinocandins fungistatic or fungicidal?

Answer 19

Can be either

Question 20

How does Griseofulvin work?

Answer 20

It accumulates in precursor keratin cells in the epidermis and prevents spread of fungal infections to unexfoliated skin cells.

It also interferes with tubulin at a molecular level. Griseofulvin prevents the assembly of microtubules (changes the shape of the tubule proteins and prevents their reassembly).

Tubulin is involved in mitosis and so Griseofulvin prevents fungal mitosis.

Question 21

Which Azoles are systemic?

Answer 21

Fluconazole and Itraconazole (Triazoles)

Question 22

Which Azoles are topical?

Answer 22

Clotrimazole, Econazole and Tioconazole