Antifungals Flashcards
Which two opportunistic fungal infections will be molds in the body?
Aspergillosis and Mucormycosis (there are no butterflies in either Sketch)
Although Aspergillus is found predominately in immunocompromised people, it is not found in those with HIV. Why?
Neutrophils can kill Aspergillus, so typically it occurs in people who are granulocytopenic.
Describe the structure of the fungal cell wall from outside to inside.
Outer surface • Mannoproteins •Beta-1,3-glucan •Chitin •Phospholipid bilayer with ergosterol Inner surface
The name amphotericin can help you remember its chemical properties: _______________.
it is amphipathic, with a nonpolar and polar section
How exactly does amphotericin work?
It binds to the hydrophobic portion of ergosterol and then the hydrophilic portion of amphotericin makes a pore that destroys the membrane gradient.
Why can’t amphotericin be orally absorbed?
It has a large hydrophobic region and will not dissolve well.
Amphotericin can be administered two ways: ________________.
intravenously or intrathecally
Patients are often premedicated with _______________ to eliminate the adverse infusion reactions.
acetaminophen or hydrocortisone
Although amphotericin is occasionally used for ____________, there are newer drugs that are more effective.
Candida
True or false: amphotericin works synergistically with the azoles.
False. Azoles inhibit the synthesis of ergosterol and amphotericin relies on ergosterol to be fungicidal, so it wouldn’t make sense to co-administer them.
The newer azoles are of the _____________ type.
triazole
How do fungi become resistant to the azoles?
They can develop efflux pumps or point mutations in CYP.
Think of a bike pump on the road to Oz.
The azoles are good for _____________ because they are orally available.
outpatient treatment
Which azole can reach the CSF?
Fluconazole (like the flying monkey with the helmet)
Ketoconazole has what two side effects?
Gynecomastia and GI upset
Fluconazole has what side effects?
GI upset, teratogen, and drug interactions
How is fluconazole metabolized?
Renally (with a long half-life of 25 hours)
Note: all other azoles are hepatically metabolized.
Voriconazole has what unique side effects?
Visual changes: loss of color vision; flashes of light
______________ are now used as empiric therapy for fungal septicemia in the immunosuppressed.
The echinocandins
The echinocandins must be given _________________.
intravenously
The dose of echinocandins must be altered in those with _____________ insufficiency.
hepatic
Echinocandins cause what side effects?
GI upset, skin rashes, and headache (relatively safe overall)
What antifungal is given as a prodrug that requires intracellular activation?
Flucytosine, which must be activated by cytosine deaminase
How is flucytosine administered?
Orally
______________, in addition to fluconazole, also distributes to the CSF.
Flucytosine
Just remember that the FLUs FLY to the CSF.
True or false: amphotericin B is commonly given to pregnant women.
True! It’s one of the only antifungals shown to be safe in pregnancy.
Describe the distribution of griseofulvin.
It is not absorbed well orally because it requires lots of fat, but because it accumulates in keratin-containing tissues it can be given orally for skin and nail infections.
What are the side effects of griseofulvin?
Headache and CYP induction
Which antifungals are fungicidal and fungistatic?
•Fungicidal:
- Amphotericin
- Terbinafine
- Echinocandins
- Nystatin
•Fungistatic:
- Griseofulvin
- Azoles
Flucytosine –not stated in the handout
Amphotericin must be dose-limited in patients with _____________.
renal impairment
True or false: IV nystatin can treat esophageal candidiasis.
False. Because of its toxicity, nystatin is limited to topical and oral treatment. It is poorly absorbed, so oral use does not lead to toxicity.
Sketchy left an important side effect out of the azoles scene: ________________.
they are teratogens
The echinocandins cannot be used to treat ______________.
CSF infections
Which is absorbed better, terbinafine or griseofulvin?
Terbinafine
Newer azoles can be used for ______________.
mucormycosis
