Classification of Antifungal Agents

Study Notes

Polyenes:
- Bind to ergosterol in fungal cell membranes, creating pores and disrupting membrane function
- Examples: Amphotericin B, Nystatin
Azoles:
- Inhibit lanosterol 14α-demethylase, blocking ergosterol synthesis
- Examples: Fluconazole, Itraconazole, Voriconazole
Allylamines:
- Inhibit squalene epoxidase, blocking ergosterol synthesis
- Examples: Terbinafine
Echinocandins:
- Inhibit β-(1,3)-glucan synthase, blocking fungal cell wall synthesis
- Examples: Caspofungin, Micafungin, Anidulafungin
Fluoropyrimidines:
- Inhibit thymidylate synthase, blocking DNA synthesis
- Examples: Flucytosine

Fungal cell membrane disruption:
- Polyenes and Azoles disrupt fungal cell membranes, leading to cell death
Inhibition of ergosterol synthesis:
- Azoles, Allylamines, and Fluoropyrimidines inhibit ergosterol synthesis, disrupting fungal cell membrane function
Inhibition of fungal cell wall synthesis:
- Echinocandins inhibit β-(1,3)-glucan synthase, blocking fungal cell wall synthesis

Broad-spectrum antifungals:
- Effective against a wide range of fungi, including Candida, Aspergillus, and Histoplasma
- Examples: Amphotericin B, Voriconazole
Narrow-spectrum antifungals:
- Effective against specific types of fungi, such as dermatophytes
- Examples: Terbinafine

Common adverse effects:
- Nausea, vomiting, diarrhea, headache
Severe adverse effects:
- Hepatotoxicity, nephrotoxicity, allergic reactions
Interactions:
- CYP450 inhibitors or inducers may affect antifungal pharmacokinetics
- Antifungals may interact with other medications, such as warfarin and statins

Polyenes bind to ergosterol in fungal cell membranes, creating pores and disrupting membrane function, with examples including Amphotericin B and Nystatin.
Azoles inhibit lanosterol 14α-demethylase, blocking ergosterol synthesis, and include Fluconazole, Itraconazole, and Voriconazole.
Allylamines inhibit squalene epoxidase, blocking ergosterol synthesis, with Terbinafine as an example.
Echinocandins inhibit β-(1,3)-glucan synthase, blocking fungal cell wall synthesis, including Caspofungin, Micafungin, and Anidulafungin.
Fluoropyrimidines inhibit thymidylate synthase, blocking DNA synthesis, with Flucytosine as an example.

Polyenes and Azoles disrupt fungal cell membranes, leading to cell death through fungal cell membrane disruption.
Azoles, Allylamines, and Fluoropyrimidines inhibit ergosterol synthesis, disrupting fungal cell membrane function.
Echinocandins inhibit β-(1,3)-glucan synthase, blocking fungal cell wall synthesis.

Broad-spectrum antifungals, including Amphotericin B and Voriconazole, are effective against a wide range of fungi, such as Candida, Aspergillus, and Histoplasma.
Narrow-spectrum antifungals, such as Terbinafine, are effective against specific types of fungi, like dermatophytes.

Common adverse effects of antifungal agents include nausea, vomiting, diarrhea, and headache.
Severe adverse effects include hepatotoxicity, nephrotoxicity, and allergic reactions.
Interactions with antifungal agents can occur with CYP450 inhibitors or inducers, affecting pharmacokinetics, and with other medications, such as warfarin and statins.