Antifungal Agents Flashcards
What do the “fungins” or eichinocandin drugs target? MOA?
Beta glucan which is component of the cell wall of
What is the MOA of azole drugs?
14-a- demethylase
Lanosterol cannot be converted into ergosterol which is needed to maintain cell membrane integrity of the fungus
What is the purpose of 14-a-demethylase?
to convert lanosterol into ergosterol
MOA of terbinafine?
inhibits squalene epoxidase
What is the purpose of squalene epoxidase?
to convert squalene to squalene epoxide and ultimately forming ergosterol to become a part of the fungal cell membrane
MOA Amphotericin B?
binds ergosterol and interacts to form artificial pores which disrupt the membrane permeability?
What are the polyene drugs for antifungals?
amphotericin B, Nystatin
What does amphotericin B remain the DOC for?
severe infection caused by cryptococcus and Mucor
What other drug does amphotericin B have synergistic action with?
flucytosine
Can Nystatin be used systemically?
no too toxic for systemic use
How is Nystatin used?
used topically for localized infections (e.g. candidiasis)
How is Amp B given to a patient?
given by slow IV infusion: poor penetration into the CNS (intrathecal possible)
What are the S/E of Amp B use?
fever chills, muscle rigor, hypotension (histamine release) occur during IV infusion (test dose advisable)
nephrotoxic
How can the S/E of administering Amp B be alleviated?
partly by pretreatment with NSAIDs antihistamines, meperidine, and adrenal steroids
Amphotericin nephrotoxicity can be diminished with what other methods?
protect by Na+ loading, use of liposomal amp B, or by drug combinations (e.g flucytosine) permitting a dec in the amp B dose
Ketoconazole indications.
DOC for paracoccidioides and backup for blastomyces and Histoplasma
Indications for fluconazole?
DOC for esophageal and invasive candidiasis and coccidioidomycosis
Prophylaxis and supression in cryptococcal meningitis
Indications for itraconazole and voriconazole?
DOC in blastomycoses, sporotrichoses, aspergillosis
Indication for clotrimazole and miconazole?
used topically for candidal and dermatophytic infection
Which “azole” is the only one that can penetrate the CSF?
fluconazole
S/E of some azole drugs?
- ketoconazole is a P450 inhibitor can decrease synthesis of steroids because P450 is needed in their production including cortisol > dec. libido, gynecomastia, menstrual irregularities; inc.
- LFTs and rare heptotoxicity
MOA flucytosine?
activated by fungal cytosine deaminase to 5-fluorouracil (5-FU) which after triphosphorylation is incorporated into fungal RNA
5-FU then form 5 fluorodeoxyuridine monophosphate (5-Fd-UMP) which inhibits thymidylate synthase > dec thymine
Toxicity associated with flucytosine associated with what?
toxic to bone marrow
MOA griseofulvin? Indications?
active only against dermatophytes (orally, not topically) by depositing newly formed keratin and disrupting microbtuble structure
Terbinafine MOA? What are the indications?
active only against dermatophytes by inhibiting squalene epoxidase > dec ergosterol
Eichinocandins MOA?
inhibit synthesis of beta-1, 2 glucan, a critical component of fungal cell walls
Indication for echinocandins?
back-up drugs give IV for disseminated and mucocutaneous Candida infection or invasive aspergillosis
