Anti-Fungals

Question 1

Affect Cell Membrane:

• Polyenes - Amphotericin, Nystatin
• M.O.A
• Use
• Toxicity

Answer 1

Polyenes

• M.O.A - bind to ergosterol and form pores in membrane, which cause electrolytes to leak out
• Use - Nystatin used topically or like mouthwash for oral thrush, Amphotericin given IV for systemic infections esp Cryptococcus meningitis with Flucytosine
• Toxicity - fever with chills, nephrotoxicity, anaemia, IV phlebitis

Given with K+ and Mg because these will be excreted in urine
Amphotericin now available with lipids to prevent nephrotoxicity

Question 2

Affect Cell Membrane:

• Imidazoles and Triazoles
• M.O.A
• Use
• Toxicity

Answer 2

Imidazoles (ketoconazole + miconazole) - topical
Triazoles (fluconazole + itraconazole) - systemic

M.O.A (for both) - inhibit 14-alpha demethylase to inhibit the conversion of lanosterol to ergosterol, therefore inhibiting ergosterol synthesis
Use - local (Imidazoles) or less serious systemic infections (Triazoles)
Toxicity - inhibit testosterone synthesis, esp ketoconazole, causing gynaecomastia, inhibit CYP450

Question 3

Affect Cell Membrane:

• Allylamines and Morpholines
• M.O.A
• Use
• Toxicity

Answer 3

Allylamines - Terbinafine (topical)

• M.O.A - inhibit fungal enzyme squalene epoxidase, which interrupts ergosterol synthesis
• Use - dermatophytes (finger and toe nail infections)
• Toxicity - GI upset, taste disturbance, rarely hepatotoxic

Morpholines

• M.O.A - decrease ergosterol production and cause an accumulation of sterol
• nail lacquer for dermatophytes

Question 4

Affect Cell Wall:

• Echinocandins (caspofungin, anidulafungin, micafungin)
• M.O.A
• Use
• Toxicity

Answer 4

M.O.A - inhibit enzyme 1,3 B-glucan synthase, which inhibits synthesis of 1,3 B-glucan, which weakens cell wall and leads to death of fungus by osmotic lysis
Use - invasive aspergillosis, candida
Toxicity - GI upset and skin rash most common

Question 5

Affect Intracellular Processes:

• Flucytosine
• M.O.A
• Use
• Toxicity

Answer 5

M.O.A - enters cell, where it is converted to 5-FU by cytosine deaminase, where it is incorporated into DNA or RNA and prevents DNA or RNA synthesis
Use - systemic infection, esp with amphotericin for C. Meningitis
Toxicity - BM supression, N+V+Diarrhoea

Question 6

Affect Intracellular Processes:

• Griseofulvin
• M.O.A
• Use
• Toxicity

Answer 6

• M.O.A - interferes with microtubule function which interrupts mitosis
• Use - dermatophytes
• Toxicity - teratogenic, carcinogenic, induces CYP 3A4