Microbiology: Antifungals Flashcards
What fungi is ‘ringworm?
Dermatophytes
Where are Superficial mycoses?
Affect the skin, hair and nails
Mucosal surfaces in upper respiratory tract
Where are Subcutaneous mycoses (Intermediate)?
Affect the muscle and connective tissue, below the skin
Where are Systemic (invasive) mycoses?
Often relate to immune suppression or other issues
Involve the internal organs
Primary versus opportunistic
Fungal cells are ……………..
Eukaryotic so unlike bacteria they have a lot more in common with the cells of the host they infect
What do fungal cell wall contain?
chitin and other polysaccharides
What is the difference in animal and fungal cell walls?
Animals have cholesterol as their sterols and fungi have ergosterol
Fungi also have glucans
What antifungals work on the membrane in general?
Polyenes (polyene macrolides) - bind and disrupt the membranes
What antifungals affect the membrane sterols?
Azoles and allylamines - interfere with ergosterol synthesis
What antifungals affect the glucans?
Echinocandins - inhibit gluten synthesis
What are the polyenes?
Nystatin and Amphotericin B
How do polyenes work?
Form pores
Preferentially bind sterols especially ergosterol.
This binding alters membrane osmotic regulation, leakage of intracellular potassium and other small molecules
Are azoles fungistatitic or fungicidal?
Azoles are only fungistatic.
What are the groups of Azoles?
Two distinct groups imidazoles and triazoles
Are azoles fast acting?
Slow rate of action - requires several generations to act
How do azoles work?
Inhibit 14-alpha-demethylase which;
o depletes ergosterol
o causes accumulation methyl-ergostadiene-diol
o methyl-ergostadiene-diol is toxic.
What do azoles work on?
Works on
o Dimorphic fungi
o Dermatophytes
Some do NOT work on:
o Aspergillus sp. (Triazoles active / azoles not)
How do allyamines work?
Inhibit squalene epoxidase
Effect:
» Reduces ergosterol production
» causes accumulation of squalene which is toxic
What are allyamines affective against?
Have board spectrum activity
Particular effective against dermatophytes
How do Echinocandins work?
Inhibits 1,3-beta gluten synthesis by non-competitive inhibition
Glucan depletion weakens the cell wall
Fungicidal and non-toxic
What do Echinocandins affect?
hyphae at their growing tips
Hyphae at branching points
In Yeasts:Buds fail to seperate from the mother cell
Also lead to osmotically sensitive fungal cells
Is there resistance to Echinocandins?
There is Intrinsic resistance in some fungal genera/species where other glucans predominate.
Cryptococcus sp. are intrinsically resistant as they have mainly 1,-3-alpha and 1,6-beta glucans
What are the nucleic acid and anti-mitotic antifungals?
Flucytosine and Griseofulvin
How does Flucytosine work?
It is degraded in. the fungal cell to
FdUMP - Inhibits DNA synthesis
FURTP - inhibits protein synthesis
