Antifungals Flashcards
Why are fungi difficult to target?
Because they are eukaryotic so similar to human cells
Give two possible drug targets for antifungals
Cell wall as human cells do not have cell walls, ergosterol because humans have cholesterol instead
Give an example of a polyene antifungal
Amphotericin B
What is the mechanism of action of amphotericin B?
It binds to ergosterol in the cell membrane and an amphotericin-ergosterol complex forms which creates pores in the cell causing it to burst due to osmotic lysis
What is nystatin used to treat?
Candida albicans infections of the skin
How is nystatin formulated?
As creams and ointments
What is the mechanism of terbinafine?
It inhibits squalene epoxidase which is the rate limiting step in ergosterol synthesis
Which step in ergosterol biosynthesis do the ‘azole’ antifungals inhibit?
Cytochrome P450 14-alpha-demethylase
Give 3 examples of ‘azole’ antifungals
Ketoconazole, miconazole, fluconazole
Why was ketoconazole recently withdrawn from systemic use?
Due to hepatotoxicity
Why is fluconazole useful for treating cryptococcal meningitis?
Because it can be absorbed into the brain
What is the mechanism of action of echinocandin antifungals?
They target 1,3-beta-glucan synthesis to prevent carbohydrate cross links being formed in the cell walls of fungi
How do antimetabolite antifungals inhibit fungal DNA and RNA synthesis?
Flucytosine is transported into fungus by fungal cytosine permease where it is converted to 5-flourouracil (an anti cancer agent) by cytosine deaminase.
