Course: Opportunistic Fungi in the Immunocompromised Patient
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Therapeutic Approaches to Fungal Disease
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5-Fluorocytosine (flucytosine or 5-FC) is a pyrimidine analog closely related to the cancer chemotherapeutic agent 5-fluorouracil (5-FU). Flucytosine is unique, since its mode of action is intracellular, instead of affecting the cell membrane. It is deaminated within the fungal cell to 5-FU and metabolized to 5-fluorouridine triphosphate (5-FUTP) and 5-fluorodeoxyuridine monophosphate (5-FdUMP). 5-FUTP is incorporated into fungal RNA in place of uridylic acid and disturbs protein synthesis. Additionally, 5-FdUMP is a potent inhibitor of thymidylate synthase, a key element in DNA synthesis. One limitation of 5-FC is the development of drug resistance by loss or mutation of the enzymes that activate the drug. This can occur readily if flucytosine is used alone; consequently, it is used primarily in combination with AmB. This combination is widely accepted as the standard induction treatment for cryptococcal meningitis, and refractory, life-threatening Candida infections, especially with nonalbicans Candida species. Apart from these indications, the spectrum of activity is fairly limited, and the drug has significant potential for toxic side effects, including hepatotoxicity and bone-marrow suppression.

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Therapeutic Approaches to Fungal
   Amphotericin B
   Lipid Formulations of Amphotericin B
   Azole Antifungal Agents
   New Azoles Undergoing Clinical Trials
   Echinocandin/Pneumocandin Agents

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Course Number: V035B.043001

This CME Expires on July 1, 2003; no tests will be accepted after this date.

This course is accredited by The University of Pittsburgh School of Medicine, Center for Continuing Education

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