Fungal Drugs

Question 1

Terbinafine

Answer 1

• Class: “fine” drug, also Allylamines and Benzylamines
• MOA: Inhibits fungal lanosterol biosynthesis (and ∴ ergosterol synthesis) by preventing the conversion of squalene to squalene epoxide (squalene → squalene epoxide → lanosterol →→ ergosterol)

Question 2

Amphotercin B

Answer 2

• Class: Polyenes
• MOA:
  
  • Binds ergosterol and creates holes in the fungal cell membrane (intercalation) → leakage of intracellular cations and proteins
• AEs:
  
  • Systemic drug so has many side effects (called “Amphoterrible” by patients)
  • Cytokine storm → fevers, chills, etc.
  • Anemia
  • Renal toxicity

Question 3

Nystatin

Answer 3

• Class: Polyenes
• MOA:
  
  • Binds ergosterol and creates holes in the fungal cell membrane (intercalation) → leakage of intracellular cations and proteins
• AEs: is only topical and ∴ has little to no toxicity

Question 4

Ketoconazole

Answer 4

• Class: Azoles
  
  • Imidazoles and Triazoles
  • Other type in this class: Fluconazole
• MOA: blocks fungal ergosterol synthesis by inhibiting 14-α-demethylase (a fungal P450), which prevents lanosterol → ergosterol

Question 5

Nikkomycins

Answer 5

• MOA:
  
  • Inhibition of chitin synthase → depletion of chitin synthase in fungal cell wall

Question 6

Echinocandins

Answer 6

• Class: “Fungins”
  
  • Examples: capsofungin
• MOA:
  
  • Inhibit β-glucan synthase → depletion of β(1,3)-glucans (zymosan) in fungal cell wall

Question 7

Flucytosine

Answer 7

• Uses:
  
  • Effective against yeasts, but not molds
  • May be used with Amphotercin B, especially to treat Cryptoccocal meningitis
  • Not used as monotherapy because otherwise the fungi develop resistance
• MOA: results in 5-FdUMP, which inhibits fungal DNA and protein synthesis

Question 8

Griseofulvin

Answer 8

• Uses: skin and nail infections
• MOA: inhibits fungal mitosis

Question 9

Fungal Cell Envelope

Answer 9

= Cell wall plus cell membrane (phospholipid bilayer with ergosterol)

• Cell wall components:
  
  • Mannoproteins
  • Zymosans (fungal sugars)
    
    • β(1,3)-glucans
    • β(1,6)-glucans
  • Chitin (= polymer of N-acetylglucosamine)
• Cell membrane components:
  
  • Ergosterol