Antifungals Flashcards
Which route of antifungal administration is most suited to the treatment of a minor fungal infection of the toenail?
topical
what is the mechanism for Amphotericin?
binding ergosterol and forming pores in the cell wall
Normal saline is infused in a patient receiving amphotericin B why?
diminish renal damage
which antifungal can produce bone marrow supression?
flucytosine
Blurring and changes in color vision or brightness (i.e., photosensitivity and photopsia) is associated with which antifungal?
voriconazole
think: voricon ~ VISION
Which organ system(s) is are likely to be affected by flucytosine?
GI
hepatic
The imidazole drug, ketoconazole, is distinguished from the triazoles, like fluconazole, by its:
lower selectivity for fungal CYPs
Which antifungal possess the broadest spectrum of anti fungal activity?
*with grain of salt
amphotericin B
Amphotericin liposomal formulations provide for what? why?
diminished renal toxicity
decreased binding of the drug to renal cells
Clinical use of which of the following antifungals would most likely give rise to gynecomastia and impotence in males?
ketoconazole
Which of the following inhibits the production of ergosterol through a non-CYP mediated event?
terbinafine
which antifungals are polyenes?
amphotericin B
nystatin (not used systemically - toxic)
whatever happened to amphotericin A?
not in clinical use
which antifungal is a flucytosine?
5-fluorocytosine
which antifungals are in the -azole//conazole family?
ketoconazole
fluconazole
itraconazole
voriconazole
name drugs that you would administer for a ifungal systemic infection
amphotericin B (polyene)
flucytosine
azoles
name systemic drugs that you would administer for a superficial fungal infection
griseofulvin
terbafine
azole (except voriconazole)
what are some topical antifungals?
nystatin (polyene)
miconazole
clotrimazole
what organ system is amphotericin B not delivered to?
CNS
which drug could build up in a pt relying on dialysis or with extreme real dysfunction? why?
amphotericin B
- not dialyzable :: would become toxic
- slow hepatic metabolism
are polyenes hydrophillic or phobic? why is this important?
they are ampiphatic
important because it allows them to bind to ergosterol and insert into fungal memb to form pore
what is the mechanism of amphotericin B (or other polyenes)?
binds to ergotserol
inserts in membrane
creates a pore
what is the reason for dose-limiting amphotericin B?
nephrotoxic effects:
- decreases GFR
- causes renal tubular acidosis
- magnesium, potassium wasting
what antifungal drug may cause anemia? why?
amphotericin B
decreases in renal formation of erythropoietin
what is the mechanism for flucytosine?
blocks nucleic acid (thus, DNA) synthesis
what are the two enzymes involved in flucytosine mechanism? why is this important?
- permease: gets drug across membrane
- cytosine deaminase: converts to 5-FU
important bc “selective toxicity” occurs; mammalian cells have low levels of these
what enzyme is blocked in the mechanism of flucytosine?
production of 5-FU inhibits
thymidylate synthase
what are the toxic effects from prolonged high plasma levels of flucytosine?
- bone marrow depression
- alopecia
- liver dysfunction
what is required for oral absorption of an azole drug?
normal gastric acidity
which azole is not distributed to the CNS?
fluconazole
which azole is eliminated by the kidneys? in what form?
fluconazole
mostly unchanged form
what is the mechanism for the azoles?
inhibit the synthesis of ergosterol :: altering fungal cell membrane permeability
what catalyzes the reaction that azoles interrupt? what kind of reaction is it?
4-alpha demethylation, a fungal CYP450
a demethylation to lanosterol
what anti-fungal is a notorious inhibitor of CYP450? this results in _____ levels of some other drugs.
ketoconazole
increased
what antifungal results in adrenal and gonadal steroids? how?
ketoconazole
inhibits CYP450 :: production of androsterone from cortisol
what conditions (from toxicity) can ketoconazole cause?
gynecomastia
menstrual irregularities
infertility
do the non-ketoconazole azos inhbit CYP450?
yes, just are more selective
what antifungal carries some potential pregnacy risk? what class is it?
voriconazole
class D (animal studies)
mechanism of action for caspofungin/echinocandins
inhibit synthesis of beta(1-3)D-glycan :: inhibit cell wall
mechanism of action for griseofulvin
interference of microtubule function :: inhibit mitosis
possibly inhibit nucleic acid synthesis
how can resistance be built up to griseofulvin?
decrease in the energy-dependent transport that the drug uses to get in fungal cell
how can resistance develop to flucytosine?
decreased activity of the target enzymes (permease and deaminase)
how can resistance develop in azoles?
changes in sensitivity of the target enzymes (14-alpha-demethylase)
how can resistance develop in amphotericin B?
decreased level of structural change
uncommon
what anti-fungal absorption is aided by high-fat foods?
griseofulvin
what antifungal drug relies on biliary excretion?
griseofulvin
what drug does griseofulvin decrease availability of? what is the consequence?
warfarin
decreased anti-coagulant effect
3 negative issues with voriconazole?
- mental confusion/CNS problems
- pregnancy risk (class D)
- photopsia (flashes of light)
what is the mechanism for terbafine/allylamines?
interrupts cell wall component ergosterol
inhibits fungal enzyme squalene monooxygenase, which causes toxic levels of squalene, which interferes with ergosterol synthesis
three major mechanisms to antifungals
- cell wall
- cell membrane (ergosterol)
- intracellular (genome replication)
which two antifungals can cause infusion reactions?
amphotericin B
echinocandins
what is a common side effect of all antifungals?
rash
which antifungal carries a risk of photosensitivity? what does this then put the pt at risk for?
voriconazole
malignancy (melanoma)
what antifungal toxicity is associated with cardiomyopathy?
itraconazole
what antifungal class is associated with QT prolongation? especially under what circumstances?
azoles
especially with drug interactions
three antifungals that can cause GI toxicity
itraconazole
posaconazole
5-FC
which antifungal has variable toxicity? what is this due to?**
vericonazole
variable toxicity due to genetic polymorphism of CYP enzyme
what CYP enzyme does vericonazole inhibit?
CYP2C19
do the (lack of) androgen side effects abate when ketoconazole is discontinued, or are the permanent?
discontinue
which antifungal is hepatotoxic at high doses?
ketoconazole
which azoles can cause QT prolongation?
fluconazole
posaconazole
voriconazole
which fungal drug has renal excretion?**
fluconazole
which antifungal drug can have high concentrations in the CSF?**
fluconazole
