Antibiotics Used in Systemic Fungal Infections Flashcards
Antifungal that acts on microtubules
Griseofuluin
Antifungal that acts on DNA
Flucytosine
Antifungal that acts on Squalene - Lanosterol
Terbinafine, Naftifine, Amorolfine
Antifiungal that acts on Lanosterol - Ergosterol
Azoles
Antifungal that acts on fungal cell wall
Echinocandins
Amphotericin B Spectrum
broad range of fungal organisms, 2nd line for Aspergillis
Amphotericin B ADE
Fever, Chills, Tachypnea, Nephrotoxicity (saline before/after), decreased K and MG, thrombophlebitis, normocytic anemia (decreased erythropoetin)
How does 5-FC enter the cell
cytosine-specific permease
MOA of 5-FC
converted to 5-FU, then to 5-dUMP, which inhibits thymidylate synthtase depriving the fungus of thymidylic acid
5-FC spectrum
a few yeasts, used mostly synergistically with amphotericin B
does 5-FC distribute in the CNS/CSF
Yes
5-FC ADE
Bone marrow suppression, hepatic dysfunction, N/V/D
Ketoconazole ADME & PK
Liver metabolized, t1/2 about 8 hrs
Fluconazole ADME & PK
Better bioavailability and CNS/CSF penetration vs ketoconazole, renal elimination
Itraconazole ADME & PK
Liver metabolised via 2C19, nonlinear PK, food decreases absorption
Posaconazole ADME & PK
Liver metabolized to gluceronide conjugates, only PO, high fat meal increases absorption & no acid effect; NO CYP INTERACTION
Itraconazole drug interactions
3A4 inhibitor
Fluconazole interactions
3A4 and 2C9 inhibitror, raises plasma levels of cyclosporine, phenytoin, tacrolimus, theophylline, warfarin
Voriconazole drug interactions
2C19, 2C9, 3A4 inhibitor
posaconazole interactions
no CYP interactions
azole ADE
hepatotoxicity, N/V/D, sin rash and alopecia, prolonged QT interval(itraconazole black box warning), visual disturbances and hallucinations (voriconazole), not used in pregnancy
echinocandin drugs
caspofungin, micafungin, anidulafungin
echinocandin MOA
inhibit synthesis of a key component of the cell wall of many filamentous fungi - beta (1,3)-D-glucan
Caspofungin antifungal activity
invasive aspergillus (2nd line after vori), systemic candida
andulafungin spectrum
systemic candida
can echinocandins be used on cry[ptococcus
NO. it has alpha1,3 and alpha 1,6 linkages in the glucan polymers and a different enzyme catalyzes the reaction.
echinocandin ADME & PK
IV only, does not cross BBB, highly protein bound, long half life (casp0 10hr, andula 26 hrs)
echinocandin ADE
generally good safefty profile, phlebitis, rash and swelling with rapid infusion, altered liver or renal lab tests, hypokalemia
