Flucytosine (5-Fluorocytosine/5-FU) – Antifungals

00:00 Let's move on to flucytosine.

00:03 Now flucytosine is a different class of medication.

00:07 It also an antimetabolite that's used in cancer chemotherapy.

00:11 It's eliminated in the urine.

00:13 So dose adjustments going to be necessary in patients who are, who have renal disease.

00:20 It is relatively narrow spectrum agent.

00:22 And it's used almost exclusively in cryptococcus neoformans infections.

00:28 The mechanism of action, it's actually included into the -- through the cell wall by a membrane permease.

00:39 And then that concentration inside the cell is actually increasing and accumulative.

00:44 It's converted by cytosine deaminase from flucytosine to 5-FU.

00:49 So 5-FU is 5 flourocytosine.

00:52 5-FU then blocks the production of thymidine through inhibiting thymidylate synthase.

00:59 So now you're starting to interfere with actual production of DNA fragments and RNA fragments.

01:06 When combined with amphotericin B or itraconazole, synergy occurs.

01:11 So you actually get a very strong combination effect with these two agents together.

01:16 In terms of toxicity there is a reversible bone marrow depression that you sometimes see, you can sometimes see alopecia as well.

01:26 So hair loss and of course liver dysfunction.