Antifungal Agents

Question 1

What are the different groups of anti-fungal drugs?

Answer 1

1. Polyenes
2. Azoles
3. Allylamines
4. Echinocandins
5. 5-flucytosine

Question 2

Which 3 groups work by their effect on ergosterol?

Answer 2

Polyenes
Azoles
Allylamines

Question 3

How do polyene drugs work? Give an example.

Answer 3

• polyenes bind directly to ergosterol.
• acts to destabilise the fungal cell membrane

examples:

1. Nystatin
2. Amphotericin B

Question 4

How do azoles work?

Answer 4

• azoles inhibit an enzyme (c14-demeythylase) involved in ergosterol synthesis (synthesis of one of the precursors)
• leads to a depletion of ergosterol

e. g.
1. Clotrimazole

Question 5

How do allylamines work?

Answer 5

• bind to another enzyme (squalene epoxide) involved in the synthesis of the ergosterol precursor squalene
• squalene is also toxic to fungal cells and accumulates and leads to rapid cell death

e. g.
1. Terbinafine

Question 6

How do echinocandins work?

Answer 6

• some fungi also have cell walls
• cell walls: consist of glucan
• echinocandins target and block glucan synthase

Question 7

How is selective toxicity avoided?

Answer 7

1. topical application
2. target specificity
   - delivery preparation as lipid formulations

Question 8

example of selective toxicity?

Answer 8

Amphotericin B toxicity

acute reaction 30 mins post infusion

Question 9

How do fungal cells develop resistance? give examples.

Answer 9

polyenes (AmB) - can have alteration of ergosterol (but reduces fungal fitness)

azoles - proteins (enzymes) can mutate

Question 10

Echinocandins oral or IV?

Answer 10

can’t take oral - as they are lipopeptides - gastric acid might break down

Question 11

tinea pedis?

Answer 11

athletes foot

Question 12

tinea corporis?

Answer 12

ring worm

Question 13

deeper mycoses?

Answer 13

candidiasis, aspergillosis, cryptococcosis