Anti-fungals Flashcards
difference btwn yeast, mold, and dimorphic fungi in terms of cellularity?
Yeast = Unicellular Mold = Multicellular Dimorphic = Yeast at BT, Mold at RT
examples of Dimorphic fungi?
Histoplasma, Blastomyces, Coccidioides (indigenous to specific areas and pt populations - ex: HIV)
How can you tell on a plate if it is growing yeast or mold?
yeast: Pasty colonies (resembles bacteria)
mold: Surface texture: Cottony/ woolly/ velvety/ granular…
Are cell membranes present in mammals? fungi?
cell wall: present only in fungicell membrane: present in both, but comprised of different compositions
What is the basic composition and function of the mammalian cell wall? is it antigenic or non-antigenic?
polysaccharide, proteins, and glycoproteins
fxn: shape, rigidity, strength and protection from osmotic shock
What is the basic composition and function of the cell membrane?
phospholipids, sterols
fxn: Protects cytoplasm, regulates intake/secretion of solutes, facilitates capsule and cell wall synthesis
How does the cell membrane composition differ btwn fungi and mammals?
fungi– contains ergosterol
mammals – contains cholesterol
knowing the compositional differences btwn the cell wall and cell membrane, what drugs can you use to target each one?
cell wall: Enchinocandins – glycan synthesis inhibitorcell membrane: Azoles or polyenes to inhibit cell membrane synthesis
- Terbinafine
MoA? Indications? Side effect?
MoA: blocks squalene epoxidase to prevent lansterol synthesis (for cell membrane)
Indication: Onychomycosis
ADR: GI upset, HA, hepatotoxicity, taste disturbance
name some ergosterol synthesis inhibitors
fluconazole
itraconazole
voriconazole
posconazole*
mechanism of “azoles”?
inhibits ergosterol synthesis by inhibiting the cytochrome p450 enzyme (14-a-demethylase) that converts lanosterol -> ergosterol (for cell membrane)
of all the azoles that we learned, which one has the poorest GI absorption/CNS penetration?
itraconazole
of all the azoles that we learned, which one has the least drug interactions?
fluconazole
indications for fluconazole?
suppression of
- cryptococcal neoforman meningitis in AIDs**
- candida albicans infections in all drug of choice
indication for itraconazole?
histoplasma
**blastomyces coccidioides
indication for voriconazole?
aspergillus
**prophylaxis during neutropenia and gvhd
indication for posconazole?
mainly zygomycosis (mucormycosis)
- *but also great activity against:
- candida albicans**
- cryptococcus**
- aspergillus- fusarium
general side effects of azoles?
- testosterone synthesis inhibitor
- liver dysfunction/hepatitis (inhibits cytochrome p450)
- increase drug conc. of drugs metabolized by cyp450
which azole is commonly associated with gynecomastia?
ketoconazole** and itraconazole (likely due displacement of steroid hormones from serum binding proteins, resulting in a net increasein free E)
which azole has a greater likelihood of hepatitis? What ADR also associated with this particular drug?
voriconazole; also associated with visual disturbances
name 2 drugs that commonly form membrane pores in fungi. What class of drugs do they fall under?
amphotericin b (deoxycolate or lipid formulations) nystatin
both fall under the polyene class
MoA for amphotericin B?
binds ergosterol (unique to fungi); forms membrane pores that allows leakage of electrolytes and proteins from the cell
“amphoTEARicin tears holes in the fungal membrane”
What must you administer with amphotericin B and why?
must give K supplements and Mg supplements because of electrolyte losses that occur as a result of altered renal tubule permeability
Why is the liposomal formulation preferred over the deoxycolate formulation of amphotericin B?
liposomal formulation decrease toxicity/adrs, but requires higher doses to achieve the same therapeutic effect
