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54 Cards in this Set

  • Front
  • Back
inhibitor of microtubules (mitotic poison)

administered orally and localizes in stratum corneum epidermidis

effective against dermatophytes, but may worsen yeast infections
Amphotericin B (AMBd)
IV polyene antifungal

combines w/ membrane sterols to alter permeability -> leak

ineffective against: pseudallescheria boydii, trichosporon beigelli, scedosporium inflatum, candidia lustianiae

causes cardiac arrhythmias w/ rapid infusion

causes nephrotoxiciy (enhanced w/ salt depletion or dehydration)

causes hypokalemia
What are the advantages of liposomal AMB products?
decreased toxicity due to slow release

improved uptake by macrophages

selective uptake by the reticuloendothelial system in liver, spleen, lung, and lymph nodes

decreased serum half-life but increased extracellular penetration

renal concentration saturable w/ little increases as dose increases
Amphotericin B (ABLC)
complex of AMP w/ 2 lipids in a 1:1 drug to lipid molar ratio -> ribbon-like structures

1000x less hemolytic than AMBd

AMB locally released by fungal phospholipases -> effective dose 4-5x higher than AMB

very high AMB concentrations achieved in RE system, though equal renal concentrations
Amphotericin B Cholesteryl Sulfate (ABCD)
1:1 complex of AMB and cholesteryl sulfate -> forms colloidal dispersion of microscopic disc shaped particles

decreased nephrotoxicity compared to AMBd, however it has increased infusion related toxicity
true liposomal product

lyphilized form of unilamellar liposomal AMB (<100 microns)

much slower uptake by RE system -> higher peak plasma levels than other AMB products

lowest rates of infusion related and nephrotoxic side effects
Flucytosine (5-FU)
oral antimetabolite

limited spectrum: candidia albicans + other candidia, cryptococcus neoformans, candidia glabrata

used primarily in combination w/ AMB in treatment of cryptoccus meningitis or alone at high strength to irrigate the bladder in treatment of yeast infections

almost never used as a single agentdue to development of resistance
oral triazole

absorption requires gastric acidity

broad spectrum antifungal
mainly used to treat aspergillus

DOC for aspergillus, sporothrix, histoplasma, blastomyces
PO and IV triazole
(usually PO b/c serum levels are equal to IV levels)

gastric acidity not required

effective in candidia septicemia, cryptococcal meningitis, coccidioidal meningitis in AIDS pts.

therapeutic indications: oral and esophageal candidiasis, candida UTI, prevention of relapse of cryptococcal meningitis, coccidioidal meningitis, durgical and nosocomial candidiasis, hepatosplenic candidiasis

resistant: candidia krusei, candidia glabrata
PO and IV broad spectrum triazole

effective against: aspergillus, scedosporium, fusarium, candida krusei, candidia glabrata
only for compassionate use
What is the mechanism of of echinocandins drugs?
inhibits (1,3)-beta-D-glucan formation

potent activity against: candidia, aspergillus, pneumocystis

synergistic w/ AMB against aspergillus and fusarium
What is the mechanism of the azol drugs?
binding of azole q/ P450 cytochrome -> complex that blocks the transformation of lanosterol to ergosterol -> decreased incorporation of ergosterol into membrane
has become one of the DOCs for treatment of dermatophyte infections, esp. finger and toenail infections
What is the mechanism of allyamine drugs?
inhibits squalene epoxidase -> decreased ergosterol synthesis

very active against dermatophytes, but poor activity against yeast
topical allyamine

active against dermatophytes, but poor against yeast
oral allyamine

active against dermatophytes, but poor against yeast
Griseofulvin is a grisan derivative produced by what fungus?
penicillum griseofulvin
What is the mechanism of griseofulvin?
inhibitor of microtubules (mitotic poision)
How is griseofulvin administered?
What is gresiofulvin mainly used for?
treatment of dermatophytes infections
Griseofulvin cannot be used to treat what?
systemic mycoses
What is responsible for AMB's toxicity?
interaction w/ cholesterol
What is responsible for AMB's therapeutic effect?
interation w/ ergosterol
What fungi are resistant to AMB?
pseudallescheria boydii
trichosporon beigelli
scedosporium inflatum
candidia lusitaniae
How is AMB administered?
What is the major adverse effect of AMB?
What accounts of the selectivity of flucytosine?
mammalian cells do not contain cytosine deaminase
(thus cannot deaminate 5-FC -> 5-FU)
What is flucytosine effective against?
candidia albicans and some other candidia sp.

cryptococcus neoformans

candidia glabrata
Why is flucytosine almost never used as a single agent?
b/c of rapid development of resistance
What is flucytosine almost always used in combination with?
AMB b/c of synergistic effect
Name the imidazoles
Name the triazoles?
What is the DOC for non-life threatening infections caused by aspergillus, sporothrix, histoplasma, and blastomyces?
How is itraconazole administered?
Absorption of ketoconizol and itraconazole requires what?
gastric acidity
How is fluconazole administered?
PO and IV
What are the CNS levels of fluconazole?
good drug for Tx of meningitis
Why is fluconazole preferentially given PO?
b/c serum levels are equivalent w/ PO or IV routes
(only give IV if problems w/ absorption)
Does itraconazole require gastric acidity for absorption?
Does ketoconazole require gastric acidity for absorption?
Does fluconazole require gastric acidity for absorption?
What is fluconazole used for?
oral and esophageal candidiasis
candidia UTI
prevention of relapse of cryptococcal meningitis
coccidioidal meningitis
surgical and nosocomial candidiasis
hepatosplenic candidiasis
What fungi are resistant to fluconazole?
candidia krusei
candidia glabrata - can be overcome w/ higher doses
How is voriconazole administered?
PO and IV
What is voriconazole effective against?
candidia krusei
candidia glabrata
What drug is only available for compassionate use?
What antifungal inhibits (1,3)-beta-D-glucan formation?
caspofungin (an echinocandin)
What are echinocandidins effective against?
What is the DOC for treatment of dermatophyte infections, esp. finger and toeneail?
Which allyamine is oral only?
Which allyamine is topical only?
What are allyamines effective against?