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Antifungal Medication

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Antifungal Medication, Antifungal, Azole Antifungal, Imidazole Antifungal, Triazole Antifungal, Echinocandin, Echinocandin Antifungal, Polyene Antifungal, Allylamine Antifungal

  • See also
  1. Topical Antifungal
  2. Fungal Infection
  • Mechanism
  • Ergosterol
  1. Most Antifungal agents selectively target Ergosterol
  2. Ergosterol is the key sterol in fungal cell membranes
    1. Ergosterol is a target of many Antifungal agents
    2. Antifungals bind, disrupt or interfering with ergosterol synthesis
  3. As with other organisms, sterols are a key component of the cell wall
    1. Contrast with Cholesterol cell walls in humans and hopanoids in Bacteria
  • Medications
  • Azoles
  1. Background
    1. Azoles inhibit the synthesis of ergosterol (key component of fungal cell wall)
    2. Azoles block sterol 14-a-dimethylase (microsomal Cytochrome P450-dependent enzyme)
      1. 14-a-dimethylase converts lanosterol to ergosterol
      2. Blocking 14-a-dimethylase, results in ergosterol depletion
      3. Ergosterol depletion results in disruption of fungal cell wall
  2. Imidazoles (primarily used topically for candida and dermatophyte infections)
    1. Clotrimazole
    2. Miconazole
    3. Ketoconazole
      1. Broad spectrum coverage and has been used systemically
      2. However is largely replaced for systemic use by newer, less-toxic triazoles
  3. Triazoles (primarily used orally for systemic Fungal Infections)
    1. Fluconazole
    2. Isavuconazole
    3. Itraconazole
    4. Voriconazole
    5. Posaconazole
  4. Adverse Effects (when used systemically, see specific agents)
    1. Gastrointestinal (e.g. Nausea, Vomiting, Anorexia) - common
    2. Adrenal Suppression
    3. Hepatotoxicity
      1. Transient rise in Liver Function Tests is common
      2. Regularly monitor for more serious hepatotoxicity
  • Medications
  • Allylamine
  1. Background
    1. Indicated in superficial dermatophyte infections resistant to imidazoles
    2. Allylamines block Ergosterol synthesis (key component in the fungal cell wall)
      1. Inhibit squalene epoxidase, the enzyme that converts squalene to ergosterol
  2. Medications
    1. Naftifine (Naftin, topical)
    2. Terbinafine (Lamisil)
      1. Topical for resistant dermatophyte infections
      2. Accumulates in nails
        1. Oral Terbinafine is the preferred agent for Onychomycosis
  • Medications
  • Polyene
  1. Background
    1. Polyenes bind to ergosterol within the fungal cell membrane
      1. Results in fungal cell Membrane Depolarization and increased permeability
      2. Fungal cell leaks key intracellular components, and ruptures
  2. Amphotericin B
    1. Preferred agent for deep Fungal Infections in pregnancy (long safety data record)
    2. Covers most medically important fungi, but with serious adverse effects (esp. nephrotoxicity)
    3. Poor oral Bioavailability, and used primarily IV (also used intrathecally and as a Bladder wash)
    4. Systemic, invasive, life-threatening Fungal Infections (including Meningitis, cystitis) and some Protozoa infections
      1. Largely replaced by newer, less toxic fungicides
      2. Candidemia
      3. Symptomatic candida cystitis or Pyelonephritis
      4. Cryptococcal Meningitis (HIV Infection, administered with Flucytosine)
  3. Nystatin
    1. Used only topically (e.g. Diaper Candidiasis) or on mucosa (e.g. Thrush)
      1. Too systemically toxic to be used IV
      2. Not absorbed from the Gastrointestinal Tract
    2. Cutaneous Candidiasis (topical Nystatin)
      1. Candida Diaper Dermatitis
      2. Candidal Intertrigo
    3. Oral Candidiasis (Thrush)
      1. First-line agent
  • Medications
  • Echinocandin (Glucan Synthesis Inhibitor)
  1. Background
    1. Echinocandins (Cyclic Lipopeptides) inhibit synthesis of beta-(1,3)-D-Glucan a key cell wall component
    2. Active against Candida species (including those resistant to Azole Antifungals) and some Aspergillus species
  2. Medications
    1. Caspofungin
    2. Micafungin
    3. Andulafungin
  • Medications
  • Miscellaneous
  1. Flucytosine (categorized as an antimetabolite)
    1. Flucytosine is a Fluorouracil prodrug, a fluorinated cytosine analog with Antifungal activity
    2. Within fungal cells, Flucytosine is deaminated to the active metabolite 5-Fluorouracil
      1. 5-Fluorouracil substitutes for the Pyrimidine uracil during RNA synthesis
      2. Inhibits fungal Protein synthesis
    3. Indications: Systemic Fungal Infections
      1. Used primarily with Amphotericin B (risk of induced resistance when used alone)
      2. Cryptococcal Meningitis
      3. CNS Candidiasis (HIV Infection)
      4. Candida Pyelonephritis
  2. Griseofulvin (categorized as a Benzofuran)
    1. Antifungal derived first in 1958 from the mold Penicillium griseofulvum
    2. Indications limited to Tinea Capitis as an alternative agent
    3. Inhibits fungal cell division by inhibiting microtubule function in Mitosis
      1. Binds tubulin in fungi and disrupts mitotic spindles
  3. Saturated Solution Potassium iodide (SSKI)
    1. Used to treat Sporotrichosis in under-resourced regions of the world
  • References
  1. (2012) Med Lett Drugs Ther 10(120): 61-8
  2. Gladwin, Trattler and Mahan (2014) Clinical Microbiology, Medmaster, Fl