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.