Antifungals

Question 1

Imidazoles (COMET-K)

Answer 1

Mech: Inhibition of cytochrome P450 14-alpha-demethylase, an enzyme that drives the production of ergosterol from lanosterol. Ergosterol is sterol that is essential in maintaining the fluidity and permeability of fungal cell membranes.

Drugs of this class display a lot of toxicity and drug interactions. For example, clotrimazole is metabolized by CYP 3A4 and can competitively inhibit the metabolism of other drugs using this CYP complex - benzodiazepines.

Miconazole (Oravig)
Clotrimazole (Mycelex)

Others Include: Oxiconazole, Econazole, Tioconazole, and Ketoconazole (COMET-K)

Question 2

Triazoles (FIT-VIP) “2nd Generation Imidazoles”

Answer 2

Mech: Inhibition of cytochrome P450 14-alpha-demethylase, an enzyme that drives the production of ergosterol from lanosterol. Ergosterol is sterol that is essential in maintaining the fluidity and permeability of fungal cell membranes.

Drugs of this class are preferred over imidazoles because they have fewer side effects and less resistance associated with them. They are considered FIRST LINE DRUGS AGAINST SYSTEMIC FUNGAL INFECTIONS. Caution with patients on benzodiazepines, warfarin, and other drugs metabolized by the cytochrome P450 system.

Dental Uses: Esophageal candidiasis, refectory/resistant candidiasis.

Fluconazole (Diflucan)
Itraconazole
Terconazole
Voriconazole (Vfend)
Isavuconazole
Posaconazole (Noxafil)

Question 3

Polyenes

Answer 3

Mech: Bind to ergosterol in fungal cell membranes causing intercalation and leakage of intracellular ions and proteins.

Fungicidal. Polyenes not effective against dermatophytes.

Amphotericin B (liposomal IV): broad spectrum for systemic use. 1st line drug for most systemic yeasts like aspergillosis, histoplasmosis, and cryptosporidium.

Nystatin: Topical only for mucocutaneous candidiasis.

Natamycin

Question 4

Allylamines (ANT)

Answer 4

Mech: Allylamines bind to and inhibit squalene epoxidase, an enzyme that catalyzes the production of precursors to lanosterol and eventually ergosterol.

Requires actively growing fungi. Fungicidal against dermatophytes only. Synergistic with -azoles.

Amorolfin
Naftifine (topical only)
Terbinafine (oral and topical)