Infectious Diseases - Antifungals

Question 1

Give the four main classes of antifungals and example of antifungal

Answer 1

1. Polyenes (amphotericin B)
2. Pyrimidine analogues (5-fluorocytosine)
3. Azoles (ketoconoazole, clotrimazole)
4. Echinocandins (caspofungin, anidulafungin)

Question 2

Mechanism of action and side effects of polyenes (amphotericin B)

Answer 2

Bind to cell membrane ergosterol forming artificial pores which allow potassium efflux and cell death. Side effects include renal toxicity up to 30%, hepatotoxicty, electrolytebdisturbance. Combination with immunosuppressants such as tacrolimus can cause additive nephrotoxicity.

Question 3

Give the mechanism of action of pyrimidine analogues (5 fluorocytosine) (antifungal class) and potential side effects

Answer 3

Binds to fungal cytosine permease which imports it into the cell where cytosine deaminase converts it to fluoroutacil which impairs nucleic acid synthesis. Side effects: marrow suppressiob and liver toxicity.

Question 4

Give the mechanism of azoles and side effects.

Answer 4

Azoles inhibit c14 alpha sterol demethylase which leads to increase sterol precursors and reduction of ergosterol. Risk of hepatotoxicity, qt prolongation, drug drug interaction as inhibitors if cyp450. Voriconazole has photosensitivity, reversible photopsia, bone marrow toxicity.

Question 5

How does echinocandins work and the side effecfs

Answer 5

Inhibit fungal wall polysaccharide B-1,3 glucan synthesis which results in fungacidal activity, aspergillus is fungalstatic. Caspofungin uses OATP-1B1 transporter requires dose reduction when used with (rifampicin, phenytoin, dexamethasone).