Antifungals Flashcards
What are the 5 processes that that antifungals interfere with?
- direct cell membrane interaction
- cell membrane synthesis
- antimetabolite - DNA/RNA synthesis
- Fungal cell wall
- microtubule function
which drugs alter cell membrane permeability?
- azoles
- polyenes
-terbinafine
fungistatic definition
inhibits fungal growth
fungicidal definition
kills fungi
which drugs affect beta-glycan in cell wall synthesis?
echinocandin
what is beta glucan?
fungal cell wall polysaccharide in human fungal pathogens
adds to structural integrity
what is fungal cell wall made from?
chitin and polysaccharides
why are fungi hard to target pharmacologically?
more similar to human cells than bacteria
creates difficulty in drugs w selective toxicity to fungal cells
which anti-fungal blocks nucleic acid synthesis?
flucytosine
which anti-fungal disrupts microtubule function?
griseofulvin
what drug class does amphotericin B belong to?
polyene
amphotericin B
contains sterol A ring binding domain
binds to ergosterol in fungi membrane
disrupts cell membrane integrity
leakage of intracellular cations
cell death
How do azole drugs work?
inhibit lanosterol 14-alpha demethylase enzyme (part of ergosterol production pathway)
→ inhibits ergosterol production
→↑ accumulation of toxic sterols
→ ↑ membrane permeability
→ inhibits fungal growth + death
How does flucytosine work?
interferes with RNA Synthesis
- converts from 5-FC form (inactive) to 5-fluorouracil 5-FU (active)
- 5-fluorouracil is extensively incorporated into fungal RNA
- this causes uncontrolled growth and death of fungal organism
What do echinocandins interfere with and what is their moa?
- inhibits beta-glucan synthase enzymes
- this weakens cell wall structure
- interferes with fungal cell wall synthesis
- cell wall lysis
What drug class does amphotericin B belong to?
- contains polyene domain
amphotericin B moa?
- polyene sterol A ring binds to ergosterol in fungal membrane
- inserts itself into fungal membrane
- loss of membrane integrity
- leakage of intracellular cations
- cell death
What does ergosterol do in the fungal cell membrane?
type of sterol needed for membrane permeability and fluidity
How is griseofulvin involved affect microtubule function?
enter dermatophyte through energy-dependent transport processes
binds to the fungal microtubules
binds to and disrupts α and β tubulin subunits
interferes with microtubule function
prevents spindle formation → no mitosis in fungi
What is candidia auris?
fungi which colonises skin, medical equipment, abiotic surfaces
Why is candida auris difficult to treat?
only three classes of antifungal drugs are available to
treat severe Candida infections: azoles, echinocandins,
and amphotericin B.
C. auris can cause bloodstream infections and even death, particularly in hospital and nursing home patients with serious medical problems.
What are major risks from Candida auris opportunistic infections?
C. auris can cause a variety of infections from superficial (skin) infections to more severe, life-threatening infections. C. auris is the most dangerous when it causes invasive infections, such as bloodstream infections.
What is an opportunistic infection?
infections that occur more often or are more severe in people with weakened immune systems than in people with healthy immune systems
