Antifungals

Question 1

What are the types of antifungal drugs?

Answer 1

1. Natural antifungals
2. Synthetic antifungals

Question 2

What are the natural antifungal drugs (or classes of)?

Answer 2

• Polyenes
• Griseofluvin
• Echinocandins

Question 3

What is the mechanism of action of polyenes?

Answer 3

• Ionophore
• Integrates into fungal PM and forms large pores in the PM (interacts with ergosterol)
• Makes PM more permeable to certain ions (e.g. K⁺) and disrupts ionic gradients

Question 4

What are examples of polyenes?

Answer 4

• Amphotericin B
• Nystatin

Question 5

What is the mechanism of action og griseofluvin?

Answer 5

Interferes with mitosis of fungal cells by binding and disrupting microtubule assemblies

Question 6

What is the mechanism of action of echinocandins?

Answer 6

• Non-competitive inhibition of 1,3-β-glucan synthase
• Inhibits synthesis of 1,3-β-glucan which is very important component in fungal cell walls

Question 7

What are examples of echinocandins?

Answer 7

• Caspofungin
• Anidulafungin
• Micafungin

Question 8

What are the synthetic antifungal drugs (or classes)?

Answer 8

• Azoles
• Flucytosine
• Terbinafine

Question 9

What is the mechanism of action of azoles?

Answer 9

• Inhibits enzyme lanosine 14α-demethylase (converts lanosterol to ergosterol) and ergosterol synthesis
• Causes ergosterol depletion, resulting in increased fluidity of PM

Question 10

What is the mechanism of action of flucysteine?

Answer 10

• Prodrug that’s converted to 5-florouracil in fungi but not mammalian cells
• 5-florouracil inhibits thymidinate synthetase and thus DNA synthesis

Question 11

What is the mechanism of action of terbinafine?

Answer 11

• Inhibits squalene epoxidase, which is involved in synthesis of ergosterol from squalene
• Causes inhibition of ergosterol synthesis and depletion

Question 12

What are examples of azoles?

Answer 12

1. Fluconazole (systemic)
2. Clotrimazole (topical)