Antifungal Agents Flashcards
What type of drug is 5-Flucytosine
Fluorinated Pyrimidine Analogue
How do Fluorinated Pyrimidine Analogues work?
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.
What type of drug are Nystatin and Amphotericin B
Polyenes
How do Polyenes work?
Bind to ergosterol (major component of the fungal cell membrane). This increases the permeability of the plasma membrane and causes oxidative damage.
What type of drug are Terbinafine and Naftifine?
Allylamine
What type of drug is Terbinafine?
Allylamine
What type of drug is Tolnaftate?
Thiocarbamate
How do Allylmines and Thiocarbamates work?
They prevent ergosterol synthesis by non-competitively inhibiting squalene epoxidase (erg1p).
Squalene epoxidase converts squalene to lanosterol (which is required for ergosterol biosynthesis).
Will the inhibition of the squalene epoxidase (erg1p) affect humans?
No. They produce lanosterol via a different enzyme
Are Allylmines and Thiocarbamates fungistatic or fungicidal?
Fungistatic
Name some Triazoles
Fluconazole, Itraconazole
Posaconazole, Terconazole, Voriconazole
Name some Imidazoles
Clotrimazole, Ketoconazole, Tioconazole
Butoconazole, Miconazole
Are Azoles fungistatic or fungicidal?
Fungistatic
How do Azoles work?
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.
How do Azoles work?
They inhibit the enzymes lanosterol 14a-demethylase (Erg11p) and CD-demethylase.
This leads to inhibition of ergosterol biosynthesis.
What type of drug are Caspofungin, Micofungin and Anidulofungin?
Echinocandins
How do Echinocandins work?
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.
Are Azoles fungistatic or fungicidal?
Fungistatic
Are Echinocandins fungistatic or fungicidal?
Can be either
How does Griseofulvin work?
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.
Which Azoles are systemic?
Fluconazole and Itraconazole (Triazoles)
Which Azoles are topical?
Clotrimazole, Econazole and Tioconazole
