Classification of Antifungal agents and Pharmacology of polyenes antibiotics

 

Classification of Antifungal Agents

Antifungal agents can be classified based on their chemical structure or mechanism of action. Here's an overview of their classification:

1. Polyenes

• Examples: Amphotericin B, Nystatin, Natamycin
• Mechanism of Action: Bind to ergosterol in fungal cell membranes, creating pores that increase membrane permeability, leading to cell death.

2. Azoles

• Examples: Fluconazole, Itraconazole, Ketoconazole, Voriconazole
• Mechanism of Action: Inhibit lanosterol 14α-demethylase (a key enzyme in ergosterol biosynthesis), causing membrane instability.

3. Echinocandins

• Examples: Caspofungin, Micafungin, Anidulafungin
• Mechanism of Action: Inhibit 1,3-β-D-glucan synthase, affecting fungal cell wall synthesis.

4. Allylamines

• Examples: Terbinafine, Naftifine
• Mechanism of Action: Inhibit squalene epoxidase, blocking ergosterol synthesis.

5. Antimetabolites

• Examples: Flucytosine (5-FC)
• Mechanism of Action: Inhibits DNA and RNA synthesis by converting to 5-fluorouracil within the fungal cell.

6. Other Antifungal Agents

• Griseofulvin: Inhibits fungal mitosis by interacting with microtubules.
• Ciclopirox: Disrupts fungal enzyme function by chelating divalent cations.

Pharmacology of Polyene Antibiotics

Polyenes are a class of antifungal agents that include Amphotericin B and Nystatin. Their pharmacology is discussed below:

1. Amphotericin B

• Mechanism of Action: Amphotericin B binds to ergosterol, a key component of fungal cell membranes. This binding creates pores or channels in the membrane, increasing its permeability. As a result, ions and molecules leak out, leading to cell death. Amphotericin B is effective against a wide range of fungi.

• Pharmacokinetics:

  • Administration: Usually given intravenously due to poor oral bioavailability.
  • Distribution: Binds extensively to tissues, leading to a large volume of distribution.
  • Metabolism: Not extensively metabolized, eliminated slowly via the kidneys.
  • Half-life: Long, up to 15 days.

• Adverse Effects:

  • Nephrotoxicity is the most common and serious side effect, potentially leading to renal damage.
  • Infusion-related reactions: Fever, chills, hypotension, and thrombophlebitis may occur during administration.
  • Electrolyte disturbances: Hypokalemia and hypomagnesemia.

• Clinical Uses:

  • Treatment of severe systemic fungal infections (e.g., Cryptococcal meningitis, Aspergillosis, Histoplasmosis).

2. Nystatin

• Mechanism of Action: Similar to Amphotericin B, Nystatin binds to ergosterol in the fungal membrane, increasing permeability and causing cell lysis. However, it is used only topically or orally for localized infections, not systemic use.

• Pharmacokinetics:

  • Administration: Available as a topical cream, ointment, or oral suspension.
  • Absorption: Not absorbed from the gastrointestinal tract or skin, so systemic effects are minimal.
  • Excretion: Primarily unchanged in the feces.

• Adverse Effects:

  • Minimal due to lack of systemic absorption; occasional skin irritation with topical use.

• Clinical Uses:

  • Oral thrush (candidiasis), cutaneous or mucocutaneous fungal infections.