Disease control Flashcards
4 major anti-fungal classes + their targets
Azoles
- cell membrane integrity
5-flucytosine
- Nucleic acid (DNA/RNA) synthesis
Polyenes
- cell membrane integrity
Echinocandins
- cell wall synthesis
Why is it difficult to treat fungal infections?
Fungi are more closely related to animals than bacteria
Polyene
- mechanism of action
Targets cell membrane by disrupting stability
Intercalates with ergosterol in cell membrane
- > creates K+ channel
- > cell contents leak out
Polyene
- produced by
- type of anti-fungal
Streptomyces
Fungicidal
Polyene
- usage
Amphotecerin B
Used to treat Cryptococcosis
BUT has renal toxicity (kidneys)
Azoles
- mechanism of action
Inhibits ergosterol biosynthesis
Targets Cytochrome P450 enzyme (lanosterol 14-alpha-demethylase)
Accumulation of toxic sterol intermediates
Azoles
- anti-fungal type
Fungistatic
- requires functioning immune system to achieve max therapeutic effect
- needs to clear the infection
Azoles
- application
In Fluconazole
Used for yeast infections
Azoles
- Voriconazole
- mechanism of action
Synthetic derivative of fluconazole
Binds tighter to lanosterol demethylase
Inhibits a 2nd enzyme in same pathway
Azoles
- Voriconazole
- type of anti-fungal
Fungicidal
Azoles
- Voriconazole
- application
Fungicidal activity on par with Amphotericin B (polyene)
Active against opportunistic moulds (Aspergillus)
5- Flucytosine
- mechanism of action
Anti-metabolite
- fluorinated pyrimidine
Blocks DNA synthesis + protein translation
Taken into cell ->Metabolised by fungal cytosine deaminase
-> becomes toxic
5-Flucytosine
- type of anti-fungal
Fungicidal
5-Flucytosine
- why don’t humans accumulate the toxic intermediate?
Don’t have the enzyme
- cytosine deaminase
5-Flucytosine
- application
Fungicidal activity inferior to Amphotericin B (polyene)
Alternative mono-therapy fo patients with fluconazole-resistant Candida sp.
Echinocandins
e. g. Caspofungin
- mechanism of action
Lipopeptides
Non-competitive inhibition of B -1,3 - glucan synthase in cell wall required for production of cell wall polysaccharides
Blocks cell wall synthesis
Fungal cells lose shape
+ become osmotically fragile
Echinocandins
- why does it not affect human cells?
B-1,3-glucans not present in humans
Echinocandins
- type of anti-fungal
Fungicidal against yeast + C. albicans
Fungistatic against moulds (A. fumigatus)
Echinocandins
- not functional against
C. neoformans
= basidiomycete
- less B-1,3- glucans