Core pharmacology

Class Group

ANTIFUNGAL:
AZOLE

Legacy Cicm Level

Level 3

Introduction

Triazole

Mechanism of action

fluorinated bis-triazole
reduction of ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes (greater affinity for fungal than for human)

Antimicrobial Spectrum

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

Resistance Mechanism

Some candida species,

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

Adverse Effects Toxicity

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)

Absorption

Well absorbed orally

Distribution

good CSF penetration

Metabolism

not metabolized well

Excretion

Urine unchanged

Special Points

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