Antimicrobials: antifungals Flashcards
What fungus is most frequently associated with oral lesions?
- Candida albicans
[mucocutaneous mycoses, thrush, denture stomatitis]
Is candida albicans the 1st most common organism isolated from US blood cultures?
NO, 4TH
HARD TO TELL IF IT IS COMMENSAL COLONIZATION OR PATHOGEN/INFECTION
What are the 2 categories of anti fungal drugs?
a. oral and parenteral drugs for systemic therapy of systemic infections b. topical drugs for local therapy, and oral drugs (for local or systemic therapy) of mucocutaneous infections
What type of anifungals bind to ergosterol ?
polyene antibiotics
What type of anifungals associates with polymerized microtubules?
griseofulvin
What type of antifungals block ergosterol synthesis? 2
- Azoles- bind fungal cytochrome P450 enzyme lanosterol 14-alpha-demethylase
- allylamine
What structure is found in amphotericin B and nystatin?
lactone ring–(macrolide) polyene antibiotics
What anti-fungal has the broadest spectrum of anti fungal activity? when is it drug of choice? fungicidal?
- Amphotericin
- most life threatening systemic fungal infections
- yes but may be static depending on environment etc.
What causes amphotericin adverse effects?
binding cholesterols [much less than ergosterol, but it does happen]
When is resistance to amphotericin B found? Is it rare?
- when ergosterol concentration is low (azole treatment etc.)
- if ergosterol affinity for amphotericin B is reduced
YES BUT MAY BE OBSERVED WITH CANDIDA SPECIES OTHER THAN C. CLBICANS
Is amphotericin absorbed well?
No- oral administration is only topical for GI
Must be parenteral for systemic infections. Not soluble
How are amphotericin metabolites excreted
renal
T-F–broad distribution of deoxycholate formulation of amphotericin B is a significant factor in toxicity?
True
What adverse effect is almost always seen to some degree with IV?
nephrotoxicity- slower with IV infusion as opposed to allergic/immediate
What 3 types of drugs have bad interactions with amphotericin B?
- digitalis
- azoles
- nephrotoxic agents [aminoglycosides and cyclosporine]
What is critical for patients with renal dysfunction or requiring long-term amphotericin B therapy?
Liposomal preparations
Can nystatin be used parenterally?
No- too toxic
No absorbed through membranes so can be used topically everywhere
What does nystatin taste like?
bitter and very unpleasant taste
Is griseofulvin static or cidal?
statis
T-F–griseofulvin induces various CYP isoforms?
True–> alters effectiveness of various drugs including warfarin and oral contraceptives
is flucytosine static or tidal? oral or parenteral?
- static
2. oral
What converts flu cytosine to 5-FU? What does 5-FU inhibit?
- cytosine deaminase
2. Nothing–> 5-FdUMP which competitively inhibits thymidylate synthetase
What do we use flu cytosine in combination with to yield a synergistic effect? what disease?
- amphotericin B -
2. Cryptococcus meningitis and severe candida
How do we get resistance to flucytosine?
mutations in cytosine permease or
cytosine deaminase
With flucytosine is oral bioavailability good? CNS penetration? hepatic excretions?
- 90%
- good CNS penetration
- Renal excretion
Are azoles static or tidal? Oral or parenteral?
- Static
2. both
T-F–triazoles are much less specific for fungal CYPs than imidazoles? T-f— numerous drug interactions overall for this class?
- False- other way around
2. True
What class of azoles is ketoconazole, miconazole, clotrimazole? Which azole has the greatest propensity to inhibit mammalian CYPS?
- Imidazoles
2. Ketoconazole- may cause symptomatic hepatitis that can be fatal and dose independent
Is micronazole often used systemically?
no- thrombophlebitis after IV
What drug class is itraconazole, fluconazole, voriconazole, posaconazole, efinazonazole?
Triazoles
Is itraconazole absorbed well in the GI?
Yes
What are 3 key resistance facts of fluconazole
- intrinsic resistance to C. krusei
- Common in C. glabrata
- Not active against mols like aspergillus
T-F– voriconazole is less potent in vitro against yeast and molds than itraconazole? Is vori oral biovailability high? Which CYP is largely effected?
- False- more potent in vitro
- yes
- CYP3A4
Does posaconazole have good oral bioavailability? what is it largely effective against?
- Yes
2. zygomycoses
Is efinaconazole safe?
YES!! mono therapy for fungal toenail infections
What anti fungal class has a terbinafine structure? are they cidal or static?
- allyamines
2. cidal
T-F– allylamines and griseofulvins have the same dermatophyte target?
True
Where does terbinafine accumulate?
in the skin, nails, and fatty tissues
Co administration of terbinafine with what doubles its clearance? decreases its clearance?
- Rifampicin
2. cimetidine
T-F–besides skin and nail infections, terbinafine is used for unusual refractory yeast infections?
False- mold infections
WHAT IS the newest class of antifungals? what does it cause to the cell wall? oral or parenteral?
- glucan synthesis inhibitors
- osmotic shock and lysis
- parenteral IV
