ML

Antimicrobial Drugs: Antifungals and Antivirals 3

Fungal Infections (Mycoses)

  • Types of Mycoses:
    • Superficial Mycoses:
    • Skin infections such as dermatophytosis (ringworm) and yeast infections like otitis externa.
    • Systemic Mycoses:
    • Internal infections including blastomycosis, histoplasmosis, and cryptococcosis.

Antifungals

  • Antifungal agents can be classified as either fungicidal (kill fungi) or fungistatic (inhibit the growth of fungi).
  • Mechanisms of action include:
    • Affecting cell wall (distinct from bacterial cell walls).
    • Affecting cell membrane (similar to animal cell membranes, leading to potential toxicity).
    • Disrupting fungal cell division.
    • Interfering with nucleic acid or protein synthesis.

Systemic Antifungals

  • Polyenes:

    • Bind to and damage the fungal cell membrane.
    • Amphotericin B:
    • Approved for use in humans.
    • Poor tissue penetration; dosing typically IV every other day or 2-3 times a week.
    • Nephrotoxic; newer liposomal formulations are less toxic.
    • Nystatin:
    • Primarily used in topical formulations or orally (not absorbed) for GI infections.

  • Imidazoles:

    • Cause leakage of fungal cell membranes; generally safer than amphotericin.
    • Examples include:
    • Ketoconazole: Also used topically.
    • Itraconazole
    • Miconazole: Available in many topical forms.
    • Fluconazole
    • Voriconazole

  • Antimetabolite Antifungal:

    • Flucytosine:
    • Interferes with RNA and protein metabolism; used in combination with amphotericin B for treating cryptococcosis in cats.
    • Adverse effects include thrombocytopenia and anemia; has a higher risk of toxicity in dogs.

Antifungals for Superficial Infections

  • Common antifungals for superficial infections:
    • Polyenes (e.g., Nystatin)
    • Imidazoles (e.g., Ketoconazole, Miconazole)
    • Griseofulvin:
    • Fungistatic; disrupts fungal cell division.
    • Administered orally for dermatophytosis, best absorbed with a fatty meal.
    • Approved for use in horses but often used off-label in humans.
    • Considered teratogenic and potentially hepatotoxic.
    • Terbinafine:
    • Inhibits cell membrane synthesis; used in combination products for treating yeast (Malassezia) otitis topically.

Antiviral Drugs

  • Treatment of viral infections is challenging due to:

    • Viruses being intracellular pathogens.
    • Potential toxicity of antiviral drugs to animal cells.
    • Virus mutation leading to drug resistance.

  • Common Antiviral Drugs (all human label):

    • Acyclovir, Oseltamivir, Idoxuridine, Trifluridine, Cidofovir:
    • Used to treat feline ocular herpes infections.
    • Famciclovir:
    • Specifically treats feline herpes virus infections.

  • Interferon:

    • Used in cats for feline ocular herpes and treating FeLV; also used in dogs for various conditions.

  • Amantadine:

    • Inhibits replication of certain strains of influenza A; old use in veterinary medicine is for chronic pain.

  • GS-441524:

    • Treatment for FIP; related to remdesivir and interferes with the copying of coronavirus RNA.