Description

Fluconazole is a synthetic triazole antifungal medication, part of the larger azole class of drugs. It is a highly water-soluble compound that can be administered orally (as tablets, capsules, or oral suspension) and intravenously. Fluconazole is distinguished from other azoles by its high bioavailability and excellent penetration into the central nervous system, making it a valuable treatment for certain systemic and central nervous system (CNS) fungal infections.

Indication

Fluconazole is indicated for the treatment and prophylaxis of a wide range of fungal infections caused by susceptible fungi, primarily Candida species. Its main indications include:

• Candidiasis:
  • Oropharyngeal and esophageal candidiasis (thrush): Often used as a first-line treatment.
  • Vulvovaginal candidiasis (yeast infections): A single-dose oral regimen is a common treatment.
  • Systemic candidiasis (candidemia): Used to treat serious bloodstream infections caused by Candida species.
• Cryptococcal Meningitis: Due to its excellent penetration into the cerebrospinal fluid, it is a key drug for the treatment and maintenance therapy of cryptococcal meningitis, especially in patients with HIV/AIDS.
• Prophylaxis:
  • It is used to prevent candidiasis in patients undergoing bone marrow transplantation who are at high risk of developing a fungal infection.
  • It is also used to prevent cryptococcal disease in patients with advanced HIV infection.

Mechanism of Action

Fluconazole’s mechanism of action is fungistatic (it inhibits fungal growth) by targeting the synthesis of ergosterol, a crucial component of the fungal cell membrane. The process can be broken down into these steps:

1. Inhibition of 14-α-demethylase: Fluconazole specifically inhibits the fungal cytochrome P450-dependent enzyme called lanosterol 14-alpha-demethylase. This enzyme is essential for converting lanosterol to ergosterol, which is a key step in the synthesis of the fungal cell membrane.
2. Disruption of Cell Membrane Integrity: By blocking this enzymatic step, fluconazole prevents the production of ergosterol. This leads to the accumulation of toxic intermediate sterols (such as 14-alpha-methyl sterols) within the fungal cell membrane.
3. Increased Permeability and Cell Death: The defective cell membrane has altered structure and function, leading to increased permeability. The membrane becomes “leaky,” causing the loss of essential cellular components and inhibiting the growth and replication of the fungus. This ultimately leads to cell death at higher concentrations.

The selective toxicity of fluconazole for fungi is due to its much higher affinity for fungal cytochrome P450 enzymes compared to human P450 enzymes, minimizing adverse effects on host cells.