Antifungals Flashcards
Name the polyenes
amphotericin B and Nystatin
MOA of polyenes
interact with ergosterol in fungal membranes to form artificial “pores” = FUNGICIDAL
Polyene resistance mech.
low ergosterol content in cell membrane
What is Amphotericin B used for?
Aspergillus, Candida, Cryptococcus, Histoplasma, Mucor, Sporothrix
What is the broadest spectrum antifungal on the market?
Amphotericin B
What antifungal is used in combo with flucytosine to treat candida and cryptococcus?
Amphotericin B
How is nystatin used?
TOPICALLY
too toxic for systemic use
How is Amphotericin B administered?
slow IV infusion
poor CNS penetration (requires intrathecal admin. in CNS infection)
slow clearance and t1/2=2 wks
How is Amphotericin B toxicity reduced?
liposomal preparation
Polyene S.E.?
dose-dependent nephrotoxicity
Most common SE of Amphotericin B?
severe fever and chills
tx with aspirin, or acetapminophen, or corticosteriods, or Meperidine
*also SE: rhinocerebral phycomycosis
What drug can cause oral candidiasis?
aerosolized beclomethasone (asthma)
MOA of azoles?
fungicidal: interfere with synthesis of ergosterol (aka 14alpha demethylase, a CYP450!)
Azole resistance?
decreased intracellular accumulation of azoles
Ketoconazole use?
co-DOC for paracoccidioides, backup for blastomycoses and histoplasma
Fluconazole use?
DOC for esophageal and invasive candidiasis and coccidioidomycoses
prophylaxis for cryptococcal meningitis
Itraconazole use?
DOC in blastomycoses, sporotrichoses, aspergillosis, backup for other mycoses
Voriconazole use?
same as Itraconazole
DOC in blastomycoses, sporotrichoses, aspergillosis, backup for other mycoses
Clotrimazole and miconazole use?
TOPICAL–> candida, dermatophytic infections
Azole admin?
oral (except clotrimazole and miconazole)
How does antacid use affect ketonazole absorption?
decreases
How does food intake affect itraconazole absorption?
increases
Drug interactions with azoles?
YES because it inhibits the P450s
SE of azoles?
decreased synthesis of steriods (cortisol, testosterone)–> decreased libido, gynecomastia, menstrual irregularities
increase LFTs
Rare hepatotoxicity
Flucytosine MOA?
activated by fungal cytosine –> 5FU –> triphosphorylation–> incorporated into fungal RNA
5FU–> 5-Fd-UMP–> inhib. thymidylate synthase–> decrease thymine (DNA)
Flucytosine resistance?
YES, if used alone
Flucytosine use?
USE WITH AMPHOTERICIN B
in severe cadidal and cryptococcal infections (enters CNS)
Flucytosine SE?
bone marrow suppression
Griseofulvin use?
active only against dermatophytes
ORAL
**distributes only where keratin is
Griseofulvin SE?
Disulfiram like rxn
Terbinafine use?
active only against dermatophytes
*may be superior to Griseofulvin in onychomyces
Terbinafine MOA?
inhib. squalene epoxidase–> decreases egosterol
Terbinafine SE?
GI distress, rash, headache, increased LFTs, hepatotox.
Caspofungins MOA?
block glucan synthesis (cell wall)
Name one Caspofungins
Micafungin
Micafungin use
invasive candidiasis and aspergillosis esp. in HIV pts
Caspofungin SE
GI distress, flushing
