Triazoles

Mechanism of action: inhibit fungal ergosterol biosynthesis

Itraconazole ***

Absorption: OK, low bioavailability (no CSF penetration)

- improved with food and low gastric pH

Uses: most potent of the azoles for systemic infections

drug of choice for persistent dermatophytic infections

effective against all types of Aspergillus infection

preferred agent for endemic mycoses (eg. Histoplasma)

Adverse effects:

- drug interactions (esp. non-sedating antihistamines)

(no effect on steroid biosynthesis; variable effect on mammalian P₄₅₀ system, less than with ketoconazole but still of potential concern)

Fluconazole

Absorption: good; used orally and IV (excellent CSF penetration)

Uses:

agent of choice for cryptococcal meningitis (unless life-threatening: use AmpB)

mucocutaneous candidiasis

prophylactically for bone marrow transplants and AIDS patients

Adverse effects: (widest therapeutic window) few and mild

concern for all azoles: newly observed emergence of resistant strains in AIDS

[resistance to azoles is otherwise fairly rare]

Voriconazole (most recently approved (2002) azole, derived from fluconazole)

Absorption: good; used orally and IV (good CSF penetration, however*)

Uses:

agent of choice for invasive Aspergillus

active against Candida (even those resistant to fluconazole), Cryptococcus and endemic mycoses, but ineffective against mucormycosis (soil saprophytes)

Adverse effects: sporadic visual disturbances* (~30%); hepatotoxicity (2-3%)

Category: Pharmacology Notes