Fungi include
- Molds, which form hyphae (Aspergillus, mucor)
- Yeasts, which remain unicellular (Candida albicans, other candida species, cryptococcus)
- Dimorphs, which change between yeast and fungus forms (histoplasma)
Fungal cells have a
- Cell wall, composed of \(\beta\)-glucans (polysaccarides) like plants
- Cell membrane, stabilized by ergosterol (rather than cholesterol)
Ergosterol and glucan represent the two pathways to selective toxicity.
Azoles (Fluconazole, posiconazole)
- Inhibit ergosterol synthesis \(\to\) loss of cell membrane integrity \(\to\) lysis
- Hepatotoxic
- Fluconazole \(\to\) yeasts (C Albicans and Cryptococcus)
- Posiconazole \(\to\) C albicans, other candida sp,, crytococcus, aspergillus, mucor
Polyenes (Amphotericin)
- Bind to ergosterol and open pores \(\to\) fluid influx \(\to\) lysis
- Active against everything except some candida species
- Hepto- and nephrotoxic, causes proximal renal tubular acidosis
Echinocadins (Anidulofungin)
- Prevent \(\beta\)-glucan synthesis \(\to\) weaken cell wall \(\to\) lysis
- Active against C albicans and other candida sp.
- Anidulofungin removed by organ-independent spontaneous degradation
- Minimal toxicity