Triazoles

Triazoles are a group of antifungals that work by inhibiting C-14 α-demethylase, which is used in the synthesis of lanosterol and ergosterol. Lanosterol and ergosterol are critical to the structure of the fungal membrane. Efflux pumps and alterations in the C-14 α-demethylase enzyme are resistance mechanisms. Drug-drug effects can occur as the medications are metabolized by the CYP450 system.  Additionally, triazoles are teratogenic so must be avoided in pregnancy. Despite their similarities, triazoles are preferred over imidazoles for systemic use due to a better side effect profile.

Class Drugs

• Fluconazole

• Itraconazole

• Posaconazole

• Voriconazole

Class Mechanism of Action

Inhibits C-14 α-demethylase, which is used in the synthesis of lanosterol and ergosterol. Lanosterol and ergosterol are critical to the structure of the fungal membrane

Class Applications

See individual drugs

Class Adverse Effects

Resistance

• Efflux pumps

• Mutations of C-14 α-demethylase gene, resulting in decreased affinity

 

Drug-drug effects

• Inhibits CYP450 system

Teratogenic

• Avoid in pregnancy

Drug Table

Drug Name	Application	Comments	Image
Fluconazole	Vulvovaginal candidiasis; Cryptococcus neoformans; Prophylaxis for systemic fungal infections for bone marrow transplant recipients	Adverse Effects; Hepatitis	"Flu Shot" "Cone" "Asshole"
Itraconazole	Blastomycosis; Sporotrichosis; Paracoccidioidomycosis; Histoplasmosis	Adverse Effects; Hepatitis; Hypokalemia; Edema; Headache; Negative inotrope (avoid in heart failure)	"Cousin It" "Rack" "Cone" "Asshole"
Posaconazole	Candida; Aspergillus; Zygomycetes; Scedosporium	Adverse Effects; -Hepatitis; -Not metabolized by CYP450; -Potent inhibitor of CYP3A4, cannot use other medications metabolized by CYP3A4 concomitantly	"Pose" "Cone" "Asshole"
Voriconazole	Invasive aspergillosis; Invasive candidiasis; Paracoccidioidomycosis; Histoplasmosis	Adverse Effects; -Hepatitis; -Visual and auditory hallucinations	"Vuori" "Cone" "Asshole"