Amphotericin B

MOA: interact w/ ergosterol (fungal component) to form "artificial pores" which disrupt the membrane permeability of the fungus

Spectrum: DOC for Aspergillus, Candida, Cryptococcus, Histoplasma, Mucor & Sporothrix 

Synergistic w/ Flucytosine in Candida & Cryptococcus infxns

SE: fever, chills, muscle rigor, hypotension (d/t histamine release so pretreat w/ antihistamine)

Dose-dependent nephrotoxicity (dec. GFR, tubular acidosis, dec. K+, Mg2+)

Nystatin

topical antifungal, too toxic for systemic use

-Azoles

ketoconazole, fluconazole, itraconazole

MOA: interfere w/ synthesis of ergosterol by inhibiting a fungal P450 enzyme (14-a-demethylase) that converts lanosterol to ergosterol

Ketoconazole

Co-DOC: for Paracoccidiodes, back up for Blastomyces & Histoplasma

Oral use in mucocutaneous candidiasis or dermatophytoses

Absorption is dec. w/ antacids

Metabolized by liver enzymes can get inhibition of P450s

SE: dec. synthesis of steroids, including cortisol & testosterone --> dec. libido, gynecomastia, menstrual irregularities

Fluconazole

DOC for esophageal/invassive candidiasis & coccidioidomycoses

Prophylazis and suppression in cryptococcal meningitis

Only one that penetrates into the CSF, eliminated via urine largely unchanged

SE: dec synthesis of steroids, including cortisol and testosterone --> dec. libido, gynecomastic, menstrual irregularities

Itraconazole

DOC in blastomycoses and sporotrichoses

Absorption is increased w/ food intake

Metabolized by liver enzymes so can inhibit P450

SE: dec. synthesis of steroids including cortisol and testosterone --> dec. libido, gynecomastia, menstrual irregularities

Clotrimazole & Miconazole

Flucytosine

MOA: Activated by fungal cytosine deaminase to 5-fluorouracil which is incorporated into fungal RNA

5-FU also forms another cmpd that inhibits thymidylate synthase --> dec. thymine

Used in combo w/ amphotericin B in severe candidal and cryptococcal infxns that enter CSF

SE: toxic to bone marrow

Griseofulvin

Active orally against dermatophytes by disrupting microtubule structure in newly formed keratin

SE: HA, thrush, peripheral neuritis, phototoxicity, potentiates EtOH

Microtubule inhibitors

1. Griseofulvin

2. Colchicine

3. Vincristine

4. Vinblastine

5. Paclitaxel

Terbinafine

Active only against dermatophytes by inhibiting squalene epoxidase --> dec. ergosterol

May be superior to griseofulvin in onychomycoses (toe/fingernail infxn)

SE: GI distress, rash, HA, inc. liver function tests