Antifungals Flashcards
superficial fungal infections
- skin, hair, nails
- bugs: trycophyton, microsporum, epidermophyton
- scalp= tinea capitis
- beard= tinea barbae
- foot= tinea pedis
opportunistc fungal infections
- aspergillosis (mold)
- mucormycosis (mold)
- cyptococcosis (yeast)
- candidiasis (yeast) –> 4th most common nosocomial
amphotericin B (mech, resistance(
- broad spectrum antifungal –> used in SEVERE, immunocomp
- MOA= holes in ergosterol containing membranes
- MOR= produce less ergosterol, or have thicker membranes
- give IV (poor oral)
- intrathecal for CSF
adverse reaction of amphotericin B
- infusion related toxicity –> fever, phlebitis, HA, hypotension
- IV saline/ hydrocortisone before infusion
- type I RTA
- anemia (effects kidneys, EPO)
- hypomagnesemia
uses of amphotericin B
- rapidly progressing fungal infections
- cryptococcus –> combine with flucytosine, follow with fluconazole
name some azoles
imidazole= ketoconazle triazole= itra, vori, posa, isavu
MOA/ MOR of azoles
MOA= inhibit ergosterol biosynth by blcok conversion of lanosterol
MOR= efflux pumps, target mutation
absorption/dist/metab of ketoconazole and itraconazole
good oral —> antacids hinder absoprtion
- dist to keratinocytes and vag secretions
- hepatic metabolism
what is itraconazole generally used for?
dimorphic fungi
-broader spectrum triazole
keto/itraconazole toxicity
- p540 inhibitor
- gynocomastia
- GI disturbance
fluconazole
-good oral absorption
-CSF!!
-renal excretion –> loooooong t1/2 (25h)
-generally well tolerated
but TERATOGENIC
-p450 inhib
two big uses of fluconazole?
cryptococcal meningitis (AIDS) cociidiodal meningitis
newer azoles….
- vori, posacon, isavuc
- good oral availability + good dist
- hepatic excretion
- long t1/2
use: voriconazole, isavuconazole
Vori= aspergillosis
-visual disturbances
isavuc= mucormycosis
caspofungin (echinochandin)
- MOA= inhibits formation of b-1-3-D-glucan (part of cell wall)
- MOR= mutation in large subunit of FKS1 gene (13bDgluc)
- uses: invasive aspergillosis (static), candidiasis (cidal)
NOT crypto
echinocandin absorp/dist/metab/tox
-IV
-good dist
-Hepatic metab, fecal excretion
-tox= GI upset, HA, ***skin rash
CAT C pregnancy
flucytosine
inhibits DNA synth: C–> U
- mammals lack cytosine deaminase
- combine with ampho B in severe infx
- good CSF dist –> CNS infx
- renal excretion
- can cause bone marrow depression in AIDS patients
griseofulvin
- disrupt mitotic spindle by binding to MT/ tubulin
- static against DERMOPHYTES (not deep infx)
- poor oral absorption –> accum in kertin precursor cells
terbinafine
- blocks ergosterol synth by inhibiting squalene epoxidase
- cidal
- dermatophytes
