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.

Polyenes specifically target fungal membranes. They bind ergosterol, which is the principal sterol in fungal membranes as opposed to cholesterol found in host membranes. This interference creates a transmembrane channel and the resultant change in permeability allows leakage of intracellular components

Well absorbed orally (except miconazole)

only administered IV

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

Poor tissue penetration. Negligable CSF or urine penetration.

Itra, Keto – 99% PB

Highly protein bound

Fluc not metabolized well
Itra, Keto – metabolized by liver

Metabolised by the liver

Fluc – Urine unchanged
Itra, Keto – Excreted bile

poorly characterized but does not accumulate in renal failure

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)

Dose related nephrotoxicity
Infusion related reactions (hypotension, fever, rigors)

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

Broad antifungal cover including candida, Cryptococcus, aspergillus and zygomyces

Antifungal

Antifungal

Antifungal

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

Polyene

Level 3

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)