Anti-fungals

Amphotericin- Polyene macrolide- Broad-spectrum- 1st line treatment for systemic fungal infections due to Candida, Cryptococcus & Aspergillus- Adverse: Fever, Chills & Nausea- Long-term therapy: renal damage- Liposomal formulations (less toxic)- Selectively toxic to ergosterol- MOA:1) Binds to ergosterol of fungal cell membrane2) Pores form in membrane3) Membrane becomes unstable4) Fungal cell constituents escapeNystatin- Polyene macrolide- Treat skin & mucous membrane infection due to C. albicans - MOA:1) Binds to ergosterol of fungal cell membrane2) Pores form in membrane3) Membrane becomes unstable4) Fungal cell constituents escapeFlucytosine -Synthetic pyrimidine antimetabolite- Less toxic than amphotericin- Active against yeast- Treat systemic candidiasis or cryptococcal infections- MOA:1) Converted in fungal cells to fluorouracil2) Fluorouracil competes with uracil 3) RNA & protein synthesis is interfered4) Synthesis of nucleic acid in fungi is inhibited as a result.- Use is limited:i) Narrow-spectrumii) Resistance to drug can rapidly developiii) Synergistic antifungal activity when taken with Amphotericin Imidazole- Broad-spectrum- Often for topical use- Treat infections due to dermatophytes OR C. albicans- Not effective against Aspergillus- MOA: i) Inhibit lanosterol 14 alpha-demethylaseii) Ergosterol synthesis is inhibited as a resultTriazole- Similar structure to imidazole- Wider antifungal activity than imidazole- Less adverse events than imidazole due to specificity- MOA:1) Inhibit lanosterol 14 alpha-demethylase2) Ergosterol synthesis is inhibited as a resultGriseofulvin- Treat some dermatophyte infections (Eg. Scalp ringworm)-MOA: Inhibits fungal mitosisTerbinafine- Allylamine- Treat dermatophyte infections of skin & nails- MOA:1) Inhibit squalene epoxide2) Ergosterol synthesis is inhibited as a result 3) Squalene accumulates, which is toxic Echinocandins -MOA:1) Inhibit Beta-(1,3)-D-glucans2) Fungal wall synthesis is inhibited as a result 3) Osmotic stress builds 4) Fungal cell lyses