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Antifungal Agents




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents

  Drugs used to treat infections caused by fungi
  • Systemic and topical




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Fungi

  • Also known as mycoses
  • Very large and diverse group of
    microorganisms
  • Broken down into yeasts and molds




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Yeasts

  • Single-cell fungi
  • Reproduce by budding
  • Very useful organisms
         – Baking
         – Alcoholic beverages




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Molds

  • Multicellular
  • Characterized by long, branching filaments
    called hyphae




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Mycotic Infections

  Four General Types
  • Cutaneous
  • Subcutaneous
  • Superficial
  • Systemic*
         *Can be life-threatening
         *Usually occur in immunocompromised host

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Mycotic Infections

  Candida albicans
  • Due to antibiotic therapy, antineoplastics,
    or immunosuppressants
  • May result in overgrowth and systemic infections




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Mycotic Infections

  In the mouth:
  • Oral candidiasis or thrush
  • Newborn infants and immunocompromised patients




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Mycotic Infections

  Vaginal candidiasis:
  • “Yeast infection”
  • Pregnancy, diabetes mellitus, oral contraceptives




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents

  Systemic
  • Examples: amphotericin B, fluconazole,
    ketoconazole, itraconazole


  Topical
  • Examples: clotrimazole, miconazole, nystatin




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents

  Broken down into four major groups based
   on their chemical structure
  • Polyenes: amphotericin B and nystatin
  • Flucytosine
  • Imidazoles: ketoconazole, miconazole, clotrimazole,
    fluconazole
  • Griseofulvin



Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents:
  Mechanism of Action
  Polyenes: amphotericin B and nystatin
  • Bind to sterols in cell membrane lining
  • Allow K+ & Mg++ to leak out, altering fungal cell
    metabolism
  • Result: fungal cell death




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents:
  Mechanism of Action
  flucytosine
  • Also known as 5-fluorocytosine (antimetabolite)
  • Taken up by fungal cells and interferes with DNA
    synthesis
  • Result: fungal cell death




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents:
  Mechanism of Action
                                           Imidazoles
       ketoconazole, miconazole, clotrimazole, fluconazole


  • Inhibit an enzyme, resulting in cell membrane
    leaking
  • Lead to altered cell membrane
  • Result: fungal cell death


Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents:
  Mechanism of Action
  griseofulvin
  • Disrupts cell division
  • Result: inhibited fungal mitosis (reproduction)




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents: Side Effects
                                     amphotericin B
                                    “Shake and Bake”
  fever                     chills                   headache          anorexia
  malaise                   nausea                   hypotension       tachycardia
  muscle and joint pain
  lowered potassium and magnesium levels

  *renal toxicity
  *neurotoxicity: seizures and paresthesias

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents: Side Effects
  fluconazole
  • nausea, vomiting, diarrhea, abdominal pain,
  • increased liver function studies

  flucytosine
  • nausea, vomiting, anorexia

  griseofulvin
  • rash, urticaria, headache, nausea, vomiting, anorexia

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents:
  Nursing Implications
  • Before beginning therapy, assess for
    hypersensitivity, possible contraindications,
    and conditions that require cautious use.
  • Obtain baseline VS, CBC, liver function
    studies, and ECG.
  • Assess for other medications used
    (prescribed and OTC) in order to avoid
    drug interactions.

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents:
  Nursing Implications
  • Follow manufacturer’s directions carefully
    for reconstitution and administration.
  • Monitor VS of patients receiving IV infusions
    every 15 to 30 minutes.
  • During IV infusions, monitor I & O and
    urinalysis findings to identify adverse
    renal effects.


Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents:
  Nursing Implications
  amphotericin B
  • To reduce the severity of the infusion-related
    reactions, pretreatment with an antipyretic
    (acetaminophen), antihistamines, and antiemetics
    may be given.
  • A test dose of 1 mg per 20 mL 5% dextrose in
    water infused over 30 minutes should be given.
  • Use IV infusion pumps and the most distal
    veins possible.


Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents:
  Nursing Implications
  • Tissue extravasation of fluconazole at the IV
    site may lead to tissue necrosis—monitor IV
    site carefully.
  • Oral forms of griseofulvin should be given
    with meals to decrease GI upset.
  • Monitor carefully for side/adverse effects.




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
Antifungal Agents:
  Nursing Implications
  Monitor for therapeutic effects:
  • Easing of the symptoms of infection
  • Improved energy levels
  • Normal vital signs, including temperature




Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

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Anti-fungal agents

  • 1. Antifungal Agents Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 2. Antifungal Agents Drugs used to treat infections caused by fungi • Systemic and topical Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 3. Fungi • Also known as mycoses • Very large and diverse group of microorganisms • Broken down into yeasts and molds Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 4. Yeasts • Single-cell fungi • Reproduce by budding • Very useful organisms – Baking – Alcoholic beverages Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 5. Molds • Multicellular • Characterized by long, branching filaments called hyphae Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 6. Mycotic Infections Four General Types • Cutaneous • Subcutaneous • Superficial • Systemic* *Can be life-threatening *Usually occur in immunocompromised host Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 7. Mycotic Infections Candida albicans • Due to antibiotic therapy, antineoplastics, or immunosuppressants • May result in overgrowth and systemic infections Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 8. Mycotic Infections In the mouth: • Oral candidiasis or thrush • Newborn infants and immunocompromised patients Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 9. Mycotic Infections Vaginal candidiasis: • “Yeast infection” • Pregnancy, diabetes mellitus, oral contraceptives Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 10. Antifungal Agents Systemic • Examples: amphotericin B, fluconazole, ketoconazole, itraconazole Topical • Examples: clotrimazole, miconazole, nystatin Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 11. Antifungal Agents Broken down into four major groups based on their chemical structure • Polyenes: amphotericin B and nystatin • Flucytosine • Imidazoles: ketoconazole, miconazole, clotrimazole, fluconazole • Griseofulvin Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 12. Antifungal Agents: Mechanism of Action Polyenes: amphotericin B and nystatin • Bind to sterols in cell membrane lining • Allow K+ & Mg++ to leak out, altering fungal cell metabolism • Result: fungal cell death Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 13. Antifungal Agents: Mechanism of Action flucytosine • Also known as 5-fluorocytosine (antimetabolite) • Taken up by fungal cells and interferes with DNA synthesis • Result: fungal cell death Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 14. Antifungal Agents: Mechanism of Action Imidazoles ketoconazole, miconazole, clotrimazole, fluconazole • Inhibit an enzyme, resulting in cell membrane leaking • Lead to altered cell membrane • Result: fungal cell death Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 15. Antifungal Agents: Mechanism of Action griseofulvin • Disrupts cell division • Result: inhibited fungal mitosis (reproduction) Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 16. Antifungal Agents: Side Effects amphotericin B “Shake and Bake” fever chills headache anorexia malaise nausea hypotension tachycardia muscle and joint pain lowered potassium and magnesium levels *renal toxicity *neurotoxicity: seizures and paresthesias Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 17. Antifungal Agents: Side Effects fluconazole • nausea, vomiting, diarrhea, abdominal pain, • increased liver function studies flucytosine • nausea, vomiting, anorexia griseofulvin • rash, urticaria, headache, nausea, vomiting, anorexia Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 18. Antifungal Agents: Nursing Implications • Before beginning therapy, assess for hypersensitivity, possible contraindications, and conditions that require cautious use. • Obtain baseline VS, CBC, liver function studies, and ECG. • Assess for other medications used (prescribed and OTC) in order to avoid drug interactions. Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 19. Antifungal Agents: Nursing Implications • Follow manufacturer’s directions carefully for reconstitution and administration. • Monitor VS of patients receiving IV infusions every 15 to 30 minutes. • During IV infusions, monitor I & O and urinalysis findings to identify adverse renal effects. Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 20. Antifungal Agents: Nursing Implications amphotericin B • To reduce the severity of the infusion-related reactions, pretreatment with an antipyretic (acetaminophen), antihistamines, and antiemetics may be given. • A test dose of 1 mg per 20 mL 5% dextrose in water infused over 30 minutes should be given. • Use IV infusion pumps and the most distal veins possible. Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 21. Antifungal Agents: Nursing Implications • Tissue extravasation of fluconazole at the IV site may lead to tissue necrosis—monitor IV site carefully. • Oral forms of griseofulvin should be given with meals to decrease GI upset. • Monitor carefully for side/adverse effects. Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.
  • 22. Antifungal Agents: Nursing Implications Monitor for therapeutic effects: • Easing of the symptoms of infection • Improved energy levels • Normal vital signs, including temperature Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.