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19 Cards in this Set

  • Front
  • Back
What are the two ways fungi may grow?
Single cells-yeast and filamentous structures-mycelia.
What does a fungal cell wall consist of?
Chitin, 1,3 beta glucan, 1,6 beta glucan, mannan and proteins.
What do superficial mycoses normally involve? What are they usually caused by?
Skin, hair, nails or mucous membranes. Dermatophytes and yeasts.
How do most antifungal agents work?
Interfere with biosynthesis or integrity of ergosterol (cell membrane), others interfere with cell wall.
What are the five classes of anti-fungal agents?
Membrane disrupting agents (polyenes), ergosterol synthesis inhibitors (Azoles, Allylamines), glucan synthesis inhibitors (Echinocandins), nucleic acid inhibitor (Flucytosine) and anti-mitotic (spindle disruption-Griseofulvin.)
What is the main example of the polyene famiy? What is it similar to? Which is its use hindered? What is the mechanism of action?
Amphotericin B.
Nystatin.
Nephrotoxicity.
Associates with ergosterol causing disruption of membrane and formation of pore leaking cations-Membrane disrupting.
What is the spectrum of activity of the polyenes? What are its typical uses?
Broad, effective against most pathogenic fungal except dermatophytes.
Treatment of invasive fungal species including invasive aspergillosis, diseminated candidiasis and Cryptococcal meningitis.
What are the side effects of polyenes including Amphotericin B? By what mechanisms? How is it given?
Toxicity-particularly nephrotoxicity.
Vascular-decrease in renal blood flow leading to drop in GFR and uremina and Tubular-distal tubular ischemia, wasting of potassium, sodium and magnesium.
Via central vein.
What do lipid preparation of AMB do? How may resistance to polyenes occur?
Significantly reduce toxicity of drug and allow larger doses to be delivered.
Defects in ERG3 gene involved in ergosterol biosynthesis, deletion/mutation in ERG6 gene involved in ergosterol biosynthesis and increased catalse activity.
What are the most widely used antifungal drugs? What are the two groups of it in clinical use? Which is more safe?
Azoles.
Imidazoles and Triazoles.
Triazoles.
What is the mechanism of action for the Azoles? What is the spectrum of activity of the Azoles?
Primarily act by inhibiting te fungal cytochrome P450 enzyme C14 14alpha-demethylase in ergosterol biosynthesis pathway.
Fluconazole has good overall activity against Candida species and Cryptococcus neoformans, Itraconazole has more mould activity and less yeast, Voriconazole and posaconzaole have broader spectrum incuding against Aspergillus, Scedosporium and Fusarium.
What are the typical uses for:
fluconazole?
itraconazole?
voricinazole?
posaconazole?
Severe mucocutaneous candida infections, disseminated candidasis and Cryptococcal meningitis.
Candida vulvovaginitis, onychomycosis, "non-severe" IFIs.
IFIs including aspergillosis, severe candida infections.
Same as vorincinazole.
What are the adverse effects of azoles? What is the major drawback of using Azoles? Which drug decreases plasma triazole levels?
Relatively safe though can cause hepatotoxicity and visual symtpoms in voriconazole.
Metabloism by CYP 450. Triazole levels affected by other drugs metabolised by this pathway, plasma levels of other drugs increase.
Rifampicin.
How may resistance occur to Azoles?
Ergosterol biosynthesis defects, efflux pumps, decreased drug import and increased drug processing.
What is the newest class of antifungal drugs to be introduced into Australia? What is their mechanism of action? What is their spectrum of activity? What is its typical use? Resistance?
Echinocandins.
Inhibit formation of glucan, essential for cell walls, but not found in mammalian avoiding toxic side effects. Fungicidal against Candida spp and fungistatic against Aspergillus species.
Unstable pts with invasive or disseminated candidiases. Not usually, may be caused by mutations in genes expressing Glucan synthase and efflux pumps.
What is the mode of action of Flucytosine? What is its spectrum of activty? What is it typical used for? Resistance?
Inhibits fungal DNA synthesis.
Some activity against Candida and good activity against Cryptococcus spp.
In combination with AMB for Cryptococcal meningitis. Rapidly if used on own.
What are Allylamines used for? What are the adverse effects?
Onchymycosis.
Common and include gastrointestinal upset, taste disturbance and transient elevation of liver enzymes.
How does Griseofulvin work? Side effects?
Causes spindle disruption and inhibits dermatophyte invasion of keratin structures. Unpleasant, many drug interactions.
Which drug is the mainstay of anitfungal Rx? Which Azole is more effective against yeasts? Which has more mould activity? What is Posaconazole used for?
Amphotericin B.
Fluconazole.
Itraconazole.
Mould prophylaxis and Rx of zygomycoses