Antifungal agents are drugs used to treat infections caused by fungi, including yeasts and molds. These infections may affect the skin, nails, mucous membranes, or internal organs. Because fungal cells are eukaryotic (similar to human cells), designing selective antifungal drugs can be challenging. However, several effective drug classes are used in clinical practice.
Classification of Antifungal Agents
1. Polyene Antibiotics
- Amphotericin B
- Nystatin
- Natrium
Mechanism: Bind to ergosterol in fungal cell membranes, creating pores that leak cellular contents.
Use: Systemic fungal infections (Amphotericin B), topical candidiasis (Nystatin).
2. Azoles
- Imidazoles: Ketoconazole, Miconazole, Clotrimazole
- Triazoles: Fluconazole, Itraconazole, Voriconazole
Mechanism: Inhibit ergosterol synthesis by blocking fungal cytochrome P-450 enzymes.
Use: Broad-spectrum antifungal activity for systemic and topical infections.
3. Allylamines
- Terbinafine
- Naftifine
Mechanism: Inhibits squalene epoxidase, decreasing ergosterol synthesis.
Use: Dermatophytosis, onychomycosis.
4. Echinocandins
- Caspofungin
- Micafungin
- Anidulafungin
Mechanism: Inhibit synthesis of β-1,3-glucan, an essential component of fungal cell walls.
Use: Invasive candidiasis, aspergillosis.
5. Antimetabolites
- Flucytosine
Mechanism: Converted to 5-fluorouracil inside fungal cells, inhibiting DNA and RNA synthesis.
Use: Combined with Amphotericin B for severe systemic infections.
6. Miscellaneous Agents
- Griseofulvin – inhibits fungal mitosis
- Potassium iodide – used for sporotrichosis
Detailed Drug Profiles
Amphotericin B
- Source: Streptomyces nodosus
- Mechanism: Forms pores in fungal membranes by binding ergosterol.
- Use: Life-threatening systemic mycoses.
- Side effects: Nephrotoxicity, fever, chills.
Ketoconazole
First orally active azole antifungal.
Mechanism: Inhibits ergosterol synthesis.
Uses: Mucocutaneous candidiasis, dermatophytosis.
Limitations: Hepatotoxicity and hormonal disturbances.
Fluconazole
- Excellent CSF penetration.
- Used in cryptococcal meningitis and vaginal candidiasis.
- Fewer endocrine side effects compared to ketoconazole.
Itraconazole
- More lipophilic and broader spectrum than fluconazole.
- Used for aspergillosis and histoplasmosis.
Terbinafine
Mechanism: Blocks squalene epoxidase, leading to toxic squalene accumulation.
Use: Fungal nail infections (onychomycosis).
Flucytosine
Mechanism: Converted to 5-FU inside fungal cells; inhibits thymidylate synthase.
Use: Severe systemic infections in combination therapy.
Echinocandins
Newest antifungal class with excellent safety profile.
Use: Candida and Aspergillus infections resistant to other drugs.
Mechanism of Action Summary
- Ergosterol binding: Polyenes
- Ergosterol synthesis inhibition: Azoles & Allylamines
- Cell wall synthesis inhibition: Echinocandins
- Nucleic acid inhibition: Flucytosine
- Mitotic spindle disruption: Griseofulvin
Therapeutic Uses of Antifungal Agents
- Dermatophytosis (Tinea infections)
- Candidiasis (oral, vaginal, systemic)
- Aspergillosis
- Cryptococcal meningitis
- Sporotrichosis
- Onychomycosis
Side Effects Overview
- Nephrotoxicity (Amphotericin B)
- Hepatotoxicity (Azoles)
- GI upset
- Hormonal changes (Ketoconazole)
Detailed Notes:
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