Antifungals

Question 1

What are the 5 processes that that antifungals interfere with?

Answer 1

1. direct cell membrane interaction
2. cell membrane synthesis
3. antimetabolite - DNA/RNA synthesis
4. Fungal cell wall
5. microtubule function

Question 2

which drugs alter cell membrane permeability?

Answer 2

• azoles
• polyenes
  -terbinafine

Question 3

fungistatic definition

Answer 3

inhibits fungal growth

Question 4

fungicidal definition

Answer 4

kills fungi

Question 5

which drugs affect beta-glycan in cell wall synthesis?

Answer 5

echinocandin

Question 6

what is beta glucan?

Answer 6

fungal cell wall polysaccharide in human fungal pathogens

adds to structural integrity

Question 7

what is fungal cell wall made from?

Answer 7

chitin and polysaccharides

Question 8

why are fungi hard to target pharmacologically?

Answer 8

more similar to human cells than bacteria

creates difficulty in drugs w selective toxicity to fungal cells

Question 9

which anti-fungal blocks nucleic acid synthesis?

Answer 9

flucytosine

Question 10

which anti-fungal disrupts microtubule function?

Answer 10

griseofulvin

Question 11

what drug class does amphotericin B belong to?

Answer 11

polyene

Question 12

amphotericin B

Answer 12

contains sterol A ring binding domain

binds to ergosterol in fungi membrane

disrupts cell membrane integrity

leakage of intracellular cations

cell death

Question 13

How do azole drugs work?

Answer 13

inhibit lanosterol 14-alpha demethylase enzyme (part of ergosterol production pathway)

→ inhibits ergosterol production

→↑ accumulation of toxic sterols

→ ↑ membrane permeability

→ inhibits fungal growth + death

Question 14

How does flucytosine work?

Answer 14

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

Question 15

What do echinocandins interfere with and what is their moa?

Answer 15

• inhibits beta-glucan synthase enzymes
• this weakens cell wall structure
• interferes with fungal cell wall synthesis
• cell wall lysis

Question 16

What drug class does amphotericin B belong to?

Answer 16

• contains polyene domain

Question 17

amphotericin B moa?

Answer 17

• 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

Question 18

What does ergosterol do in the fungal cell membrane?

Answer 18

type of sterol needed for membrane permeability and fluidity

Question 20

How is griseofulvin involved affect microtubule function?

Answer 20

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

Question 21

What is candidia auris?

Answer 21

fungi which colonises skin, medical equipment, abiotic surfaces

Question 22

Why is candida auris difficult to treat?

Answer 22

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.

Question 23

What are major risks from Candida auris opportunistic infections?

Answer 23

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.

Question 24

What is an opportunistic infection?

Answer 24

infections that occur more often or are more severe in people with weakened immune systems than in people with healthy immune systems