Antifungal Therapy

Antifungal Classes - Mechanism Masters

• Polyenes (Amphotericin B, Nystatin)
  • Bind ergosterol → form membrane pores → cell lysis.
  • 📌 Polyenes POKE holes.
• Azoles (Ketoconazole, Fluconazole, Itraconazole)
  • Inhibit lanosterol 14-$\alpha$-demethylase → block ergosterol synthesis.

  ⭐ Azoles inhibit lanosterol 14-alpha-demethylase, a key enzyme in ergosterol biosynthesis.

• Allylamines (Terbinafine)
  • Inhibit squalene epoxidase → block ergosterol synthesis (earlier step).
• Echinocandins (Caspofungin)
  • Inhibit $\beta$-(1,3)-D-glucan synthase → disrupt cell wall synthesis.
  • 📌 EchinoCANdins target the CANopy (cell wall).
• Griseofulvin
  • Binds tubulin → disrupts microtubules → inhibits mitosis.
• Flucytosine (5-FC)
  • Converted to 5-FU in fungi → inhibits DNA/RNA synthesis.

Skin Savers - Topical Titans

• Azoles: Generally fungistatic. MOA: Inhibit ergosterol synthesis (↓14-α-demethylase).
  • Imidazoles: Clotrimazole, Miconazole, Ketoconazole (shampoo). Spectrum: Dermatophytes, Candida.
  • Triazoles: Luliconazole, Efinaconazole.
• Allylamines: Fungicidal (dermatophytes). MOA: Inhibit squalene epoxidase.
  • Terbinafine, Naftifine. Use: Tinea infections.
• Polyenes: MOA: Bind ergosterol, form pores.
  • Nystatin (Candida), Amphotericin B (topical, rare).
• Others:
  • Ciclopirox: Broad spectrum, fungicidal. Unique MOA.
  • Tolnaftate: Dermatophytes only.
  • Whitfield’s Ointment (Benzoic acid): Keratolytic.

⭐ Topical Terbinafine (allylamine) is fungicidal, whereas topical azoles are generally fungistatic against dermatophytes.

Systemic Soldiers - Deep‑Dive Defenders

• Griseofulvin:
  • Fungistatic (mitotic spindle inhibitor). Dermatophytes ONLY.
  • Tinea capitis, widespread tinea. Dose: 500-1000 mg/day (micro).
  • 📌 "Greasy" - ↑ absorption with fatty meal.
• Terbinafine (Allylamine):
  • Fungicidal (squalene epoxidase inhibitor). Dermatophytes, some Candida.
  • Onychomycosis (DOC), tinea corporis/pedis. Dose: 250 mg/day.
  • Fingernails 6 wks, toenails 12 wks.
• Itraconazole (Azole):
  • Fungistatic (inhibits 14-α-demethylase). Broad: Dermatophytes, Candida, Malassezia.
  • Onychomycosis (pulse: 200 mg BID, 1 wk/month), tinea versicolor.

  ⭐ Itraconazole exhibits significant drug interactions by inhibiting CYP3A4; co-administration with statins like simvastatin is contraindicated.

• Fluconazole (Azole):
  • Fungistatic (inhibits 14-α-demethylase). Candida, Cryptococcus, some dermatophytes.
  • Mucocutaneous candidiasis. Tinea (weekly 150-300 mg).
  • Vaginal candidiasis: 150 mg single dose.

Tinea Tactics - Regimen Blueprints

• Principle: Localized → Topical. Extensive/Hair/Nails/Resistant → Systemic.
• Topical (apply 1-2x daily, 2-4 wks):
  • Azoles (Clotrimazole, Ketoconazole)
  • Allylamines (Terbinafine)
  • Ciclopirox; Selenium Sulfide/Ketoconazole shampoo (versicolor, capitis adjunct)
• Systemic (duration site-dependent):
  • Terbinafine: 250mg OD. Dermatophyte DOC. (Fingernails 6 wks; Toenails 12 wks)
  • Itraconazole: Broad spectrum. Pulse/Continuous.
  • Griseofulvin: T. capitis (children). 10-25 mg/kg/day.
  • Fluconazole: Weekly (e.g., T. corporis/pedis 150mg/wk x 2-4 wks); T. versicolor (300mg x 2 doses, 2 wks apart).
• Specifics:
  • T. Capitis: Systemic (Griseofulvin/Terbinafine) + Antifungal shampoo.

    ⭐ Griseofulvin is the drug of choice for tinea capitis in children and its absorption is enhanced with a fatty meal.

  • T. Unguium: Systemic preferred (Terbinafine/Itraconazole).
  • T. Versicolor (Extensive/Recurrent): Oral Fluconazole/Itraconazole.

High‑Yield Points - ⚡ Biggest Takeaways

• Topical azoles & allylamines: first-line for most superficial dermatophytoses.
• Oral terbinafine: DOC for onychomycosis & extensive tinea.
• Oral itraconazole: broad-spectrum; for tinea versicolor, onychomycosis.
• Griseofulvin: mainly for tinea capitis in children (fatty meal aids absorption).
• Fluconazole: effective for Candida infections and some dermatophytes.
• Monitor LFTs with long-term oral antifungals (terbinafine, itraconazole, ketoconazole).
• Oral ketoconazole: high hepatotoxicity & drug interaction risk; topical preferred.