Wednesday, March 13, 2013

Antifungal Drugs

Both ergosterol and cholesterol synthesis go from squalene to lanosterol to zymosterol, which is their final common precursor.

Amphotericin B

  • This has a special hydrophobic polyene unit that binds ergosterol in the membrane.  Forms pores.  Selectivity is poor – Amphotericin B also binds cholesterol. 
  • Toxicity is Shake ‘n’ Bake.
  • Used against deep fungal infections like invasive Aspergillosis or disseminated Candidiasis.

Nystatin is a topical preparation of Amphotericin B that treats cutaneous/mucosal Candidiasis.
It is often referred to as “swish and swallow.”


  • Block lanosterol  ergosterol by inhibiting 14-α-demethylase.  Cell membranes increase in permeability.
  • Side effects: include severe hepatotoxicity.

Orally available, degraded in the liver.  Good alternative to Amphotericin B.


  • Good penetration into CSF and the eye.  Half-life of two days. 
  • This fungicide will kill Cryptococcus and prevent Candida infections. 
  • Often used in HIV-positive patients

These block an earlier step in ergosterol synthesis (squalene  lanosterol), but doesn’t seem to have any effect on cholesterol synthesis.

Flucytosine (5FC):

  • 5FC is converted to 5-FU, so it is a uracil analog. It is converted either to 5-FUMP which is incorporated into fungal mRNA, or to 5-F-dUMP which inhibits thymidylate synthase.
  • *This is an excellent example of selective toxicity, because our cytosine deaminase can’t convert it to 5-FU but fungi can!  Toxicity may arise by metabolism of 5FC to 5-FU by normal GI flora.
  • Resistance is common, so it is used with Amphotericin B.  
  • Treats Candida and Cryptococcus.


  • Disrupts all microtubules, but it’s only actively transported into fungal cells, so that’s the selective toxicity. 
  • Unique distribution to keratin, so it is used to treat hair/nail/skin infections.


  • Blocks formation of glucan polymers, so cell walls cannot form.
  • Broad spectrum, very high specificity.
  • Fights invasive Aspergillus and Candidiasis infections.

No comments:

Post a Comment