Binds to ergosterol and forms pores in the cell membrane, leaking intracellular ions & macromolecules, leading to cell

death.

Exploits the difference in lipid composition of fungal (ergosterol) and mammalian (cholesterol) cell membranes.

Immediate: fever, chills, muscle

spasms, vomiting, headache,

hypotension

Cumulative: renal damage,renal failure (irreversible component from renal tubular injury and subsequent dysfunction)

Broadest action: localized and systemic candidemia, Cryptococcus, Histoplasma, Blastomyces, Coccidioides, Aspergillus

Often used as initial regimen to rapidly ↓ fungal burden (then replaced by an azole for chronic therapy or prevention of relapse).

Converted intracellularly to FdUMP (inhibits DNA synthesis) and FUTP (inhibits RNA synthesis).

Human cells can't convert the drug into its active metabolites.

Metabolized to a toxic

compound - fluorouracil

Bone marrow toxicity (anemia,

leukopenia, thrombocytopenia),

enterocolitis

Use w. amphotericin B

(cryptococcal meningitis) or

Itraconazole (chromoblastomycosis)

Pores from amphotericin B

enhance flucytosine cell access!

Blocks fungal P450 enzymes and interferes with ergosterol synthesis

Poorly selective, interferes with mammalian P450 function;

Inhibits P450

Minor GI upset, abnormal liver

enzymes

1^st oral azole = poor selectivity.  Broad spectrum but toxicity restricts use to topical therapy.

Interferes with steroid hormone synthesis

Blocks fungal P450 enzymes and interferes with ergosterol synthesis

Much more selective

Low toxicity

Broad spectrum: Candida, Cryptococcus, blastomycosis, coccidioidomycosis, histoplasmosis

Blocks β-glucan synthase. Inhibits synthesis of β(1-3)-glucan,

resulting in disruption of the fungal cell wall and cell death.

Minor GI effects, flushing

Elevated liver enzymes when

taken w. cyclosporine

Candida, empiric antifungal

therapy during febrile neutropenia

Fungistatic

Must be administered for 2–6 weeks for skin and hair infections to allow the replacement of infected keratin by the resistant structures.

Allergic syndrome (like serum

sickness), hepatitis

Drug interactions w. warfarin &

phenobarbital

Rx: dermatophytosis (ringworm)

Fungicidal

Interferes w. ergosterol biosynthesis by inhibiting squalene epoxidase, leading

to accumulation of squalene (a sterol), which is toxic to the organism.

GI upset, headache

Rx: dermatophytoses, esp.

onychomycosis

Polyene macrolide like amphotericin B, but too toxic for parenteral administration and is only used topically.

Not absorbed significantly from skin, mucous membranes, or GI = little toxicity.

Unpleasant taste

Rx: candida (oropharyngeal

thrush, vaginal candidiasis)