Azoles disrupt ergosterol production by interacting with 14-alpha demthylase, a cytochrome P450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of fungal cell membranes, inhibition of its synthesis leads to increased cell permeability causing leakage of contents.

Well absorbed orally (except miconazole)

Fluc – good CSF penetration
Itra, Keto – no CSF penetration

Itra, Keto – 99% PB

Fluc not metabolized well
Itra, Keto – metabolized by liver

Fluc – Urine unchanged
Itra, Keto – Excreted bile

Fluc: N/V/D, Abdominal pain
Headache
Skin rash
Reversible alopecia
Rare: Hepatic failure, SJS
Should be avoided in Pregnancy
Drug interactions: (inhibitor of CYP3A4, CYP2C9)

Fluc: Candida
Cryptococcus
Coccidia
(No activity against histoplasma, blasto, sporotrichosis, Aspergillus, mucormycosis)

Antifungal

Antifungal

Triazoles: Fluconazole, Itraconazole, Voriconazole, Posaconazole
Imidazoles: Clotrimazole, Ketoconazole

Level 3

Level 3

Fluc: Some candida species,

Decreased drug concentration
Target site alteration
Up-regulation of target enzyme
Development of bypass pathways

potent CYP inhibitors with a wide range of drug interactions (including warfarin)