Antifungals Flashcards
Which vehicle of application for a topical drug is the best for drug delivery?
ointment
What is the typically therapy for widespread tinea infections?
In order of effectiveness: All oral
- Terbinafine
- Itraconazole
- Fluconazole
- Griseofulvin
What is the typical therapy for localized tinea infections?
Topical: Azoles Terbinafine Naftifine ciclopirox *Acronym: CANT
What is the typical therapy for Onychomycosis?
- Terbinafine
- Griseofulvin
- Itraconazole
- Fluconazole
(griseofulvin jumps from 4 to 2 for onychomycosis)
*Acronym: TGIF!
What topical therapy is used for onychomycosis?
Ciclopirox
Amorolfine
What is the MOA of ciclopirox?
Ciclopirox blocks fungal transmembrane transport, as a result important things cannot be taken into the cell by the fungus. Furthermore, high concentrations may destabilize the fungal membrane and lead to leakage
What ADEs should be considered with itraconazole?
- negative inotropic action
- hepatotoxicity (watch those LFTs)
- Cat C and breast milk (probably shouldn’t take
with babies)
What is the MOA of itraconazole?
Same as the other azoles it inhibits the synthesis of ergosterol (blocks fungal P450s).
T or F Itraconazole has relatively few drug-drug interactions?
F - Itraconazole is known to have CYP interactions therefore use with other drugs should be minimized. (CYP3A4)
Which 3 anti-fungal drugs are known to cause QT prolongation?
Fluconazole
Psoaconazole
Voriconazole
Which anti-fungal is associated with visual disturbances?
Voriconazole
Which 4 anti-fungals cause hepatotoxicity?
Fluconazole
Posaconazole
Voriconazole
Itraconazole
What makes taking Posaconazole inconvenient?
Posaconazole must be administered with full meal or acidic carbonated drink for adequate bioavailability
Can fluconazole, Posaconazole, and voriconazole be taken during pregnancy?
All three are contraindicated in pregnancy:
Fluconazole-Cat D
Voriconazole-Cat D
Posaconazole-Cat C
Which anti-fungal requires dose adjustment with renal failure?
Fluconazole
Which antifungals undergo hepatic elimination?
Posaconazole
Voriconazole
What factor is necessary for the azoles to enter the CSF?
P-gp
Which antifungals enter the CNS?
Fluconazole > voriconazole > Itraconazole
What is important to remember about the metabolism of Griseofulvin?
It undergoes extensive hepatic metabolism resulting in 4 effects:
- decreases effect of anticoagulants (warfarin)
- decreases contraceptive effect
- decreases cyclosporin serum levels
- increases alcohol effects
(Gets you drunk, gets you knocked up, then makes you bleed)
What is the MOA of terbinafine?
terbinafine inhibits ergosterol synthesis by inhibiting squalene epoxidase, an enzyme that is part of the fungal cell membrane synthesis pathway
What is special about terbinafine?
Typically well tolerated. Some neutropenia and lymphopenia may be noted especially in immunocompromised patients. Cat B
What is the MOA of Naftifine?
unknown
What is different about naftifine’s utility when compared with other antifungals?
naftifine is locally bactericidal
It is also anti-inflammatory
T or F: One should not mix Naftifine with the Azoles?
T: Naftifine inhibits sterol synthesis at an earlier stage thus causing pharmacodynamic interference and reducing the effectiveness of the azoles.
