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
Indications for amphotericin B?
serious systemic mycoses
- cryptococcus
- blastomyces
- coccidiodes
- histoplasma
- candida
- mucormycosis
- fungal meningitis (intrathecal)
ADRs of amphotericin B? What is cool about these particular symptoms?
ampho“terrible”: fever, chills/rigors “shake & bake” hypotension nephrotoxicity** anemia (due to decr. EPO) iv phlebitis
most of these symptoms can be prevented with prophylactic treatments (ie aspirin, diphenhydramine, hydrocortisone, slow infusion)
MoA for nystatin?
same mxn as amphotericin b - tears holes in the membrane
how is nystatin administered?
topic administration - too toxic for systemic use!
nystatin indications?
“swish and swallow”
oral candidiasis
diaper rash
vaginal candidiasis
antifungals that inhibits cell wall synthesis? What class do they fall under?
caspofungin
micafungin
all fall under the echinocandins class
MoA for caspofungin?
inhibit cell wall synthesis by inhibiting synthesis of ß1,3-d-glucan
Indications for caspofungin?
- invasive aspergillosis (3rd line rx)
- candida resistant to azoles or azole-allergic patients
ADR for caspofungin?
gi upset flushing (due to histamine release)fever, rash, n/vphlebitis,hepatits
nucleic acid synthesis inhibitors used as a anti-fungal therapy?
5-flucytosine*
MoA of 5-flucytosine?
inhibit DNA/RNA biosynthesis via conversion to 5-FU by cytosine deaminase
5-flucytosine is often used in combination with..?
amphotericin b
Indications of 5-flucytosine?
systemic fungal infections (cryptococcus meningitis)
ADR of 5-flucytosine
bone marrow suppression