The actual antifungal treatments Flashcards
what does caspofungin do?
caspofungin is a cell wall synthesis inhibitor which stops the production of glucans usually UDP-glucan is added on to an chain of glucans using glucan synthetase the caspofungin is a type of echinocandin which stops this. this kills the fungi when they try and septate at places like the hyphal tips as well as making the fungal cells vulnerable to osmotic lysis
which two drugs are an example of a chitin synthetase inhibitor?
Nikkomycin and polyoxin
NP
No problem killing the fungi
what does amphotericin B and Nystatin do and what kind of drugs are they?
Amphotericin B and Nyastin are polyenes. they are used to disrupt the plasma membrane of the fungal cell. its produced by streptomyces it has a hydrophobicand a hydrophilic side the hydrophilic side has hydroxyl groups the side of the molecule that has a large amount of double bonds is hydrophobic. the molecule inserts itself into the membrane by interacting with the sterols in the membrane. this leads to the formation of a pore in the plasma membrane. ions can then pass through the pore which disrupts the ionic control in fungal cells (K+, H+) and damages the metabolism of the fungal cells and kills the fungus
what is amphotericin B used to treat?
serious infections - you would only use this when absolutely necessary because this drug does damage the kidneys and the liver
what is Nystatin used to treat?
superficial infections
why is ergosterol different to cholestrol?
the fungal sterols are different because they are demethylated.
what does ketonazole do and what kind of drug is it?
this is a type of azole.
it binds to cytochrome p450 which is needed for the functioning of sterol demethylaseThis disrupts the fungal plasma membrane
what does 5 Fluorocytosine do?
this is a nucleoside analogue. the 5FU gets through the membrane using cytosine permease and then when it gets into the cell it gets converted into 5FU this can become two things 5Fdeoxyuridinemonophosphate which inhibits thymidylate synthase and therefore thymidine formation which blocks DNA synthesis of the 5FU gets made into 5fluoruridine triphosphate when this gets incorportated into DNA this disrupts protein synthesis.
why does the 5FU not harm eukaryotic cells?
this does not get taken up as quickly by our cells so it does not reach harmful concentrations in our cells and mammalian cells cannot make the 5FC into 5FU
how does resistance to azoles arise?
if sterol demethylase is upregulated or if there is a change in the sequence of the target enzyme or if there is a upregulation of efflux pumps
how may resistance to the polyenes arise?
if there is a mutant with low ergosterol in their membrane or if there is a sterol other than ergosterol in the membrane.
how may resistance to 5FU happen?
loss of cytosine permease.
what does griseofulvin do?
this is used to treat ringworm and fungal infections of the skin and nails when antifungal creams have not worked. The drug works by binding to tubulin which makes up the microtubules of living cells. this interferes with microtubule formation and therefore mitosis. or it binds to keratin in keratin precursor cells which makes them resistant to fungal infection . when the keratin griseofulvin complex reaches the skin or the hair the complex is able to then enter the dermatophyte and disrupt its microtubules.
