Polyene Antifungals Mechanism Quiz

Echinocandin and Pneumocandin

• Echinocandin and Pneumocandin specifically inhibit the synthesis of beta-1,3-glucan in fungal cell walls.
• Their main target in fungal cells is the enzyme 1,3-beta-D-glucan synthase, crucial for cell wall integrity.

Squalene Epoxidase Inhibitors

• Squalene Epoxidase Inhibitors target the enzyme squalene epoxidase, which is involved in ergosterol biosynthesis in fungi.
• These inhibitors result in reduced levels of ergosterol, causing disruption in fungal cell membrane integrity.

Allylamines and Related Compounds

• Allylamines and related compounds primarily affect fungi by inhibiting the enzyme squalene epoxidase, which is essential for sterol synthesis.
• Their spectrum of activity is predominantly narrow, primarily targeting dermatophytes and certain yeasts.

Polyenes Antifungal Activity

• Polyenes, such as Amphotericin B and Nystatin, act on fungal cells by binding to ergosterol in the cell membrane, leading to the formation of pores.
• This pore formation causes increased cell permeability and ultimately results in cell death due to leakage of essential cellular components.

Nephrotoxicity and Immune Effects

• Amphotericin B is known to cause nephrotoxicity, which can lead to renal impairment in patients.
• It also has a toxic effect on host immune cells, potentially leading to an inflammatory response that further complicates treatment.

Mechanism of Action for Polyenes

• Upon binding to cell membranes, polyenes like Amphotericin B form transmembrane channels that disrupt homeostasis.
• Polyenes exhibit a higher binding preference for fungal membranes compared to mammalian membranes, which mitigates some toxicity.

Toxicity and Monitoring

• Key toxic effects associated with polyenes include renal toxicity and electrolyte imbalances.
• It is crucial to monitor renal function in patients on polyene therapy due to the risk of nephrotoxicity associated with these antifungals.

Common Characteristics of Polyene Toxicities

• Toxicities observed with polyenes such as Nystatin and Amphotericin B often include nausea, fever, chills, and renal impairment across patients.

Test your knowledge on the mechanism of action of polyene antifungal drugs such as Natamycin, Amphotericin B, and Nystatin. Learn how these drugs bind to ergosterol in fungal cell membranes, leading to pore formation and cell death. Prepared based on Dr. Ghaith Mansour's lecture at Al-Balqa Applied University.