Antifungal Agents

Antifungal Agents

What Is a Fungus?

  • Fungus
    • Composed of a rigid cell wall made up of chitin and various polysaccharides, and a cell membrane containing ergosterol
    • Protective layers of the fungal cell make the organism resistant to antibiotics

Patients Susceptible to Fungal Infections

  • Patients with AIDS and AIDS-related complex (ARC)
  • Patients taking immunosuppressant drugs
  • Patients who have undergone transplantation surgery or cancer treatment
  • Members of growing elderly population no longer protected from environmental fungi

Culture

  • Culture is needed prior to prescribing antifungal agents
  • Patients on antifungal agents are immuno-compromised at onset

Amphotericin B Indications

  • Aspergillosis
  • Leishmaniasis
  • Cryptococcosis
  • Blastomycosis
  • Moniliasis
  • Coccidioidomycosis
  • Histoplasmosis
  • Mucormycosis
  • Candida infections (topically)

Amphotericin B

  • Indications: progressive, potentially fatal fungal infections
  • Pharmacokinetics: IV form, excreted in the urine
  • Contraindication: kidney disease
  • Adverse reaction: kidney failure

Systemic Antifungal Agents

  • Caspofungin (Cancidas) (IV)
    • Approved for the treatment of invasive aspergillosis in patients who are refractory to other treatments
  • Flucytosine (Ancobon) (oral)
    • Less toxic drug used for the treatment of systemic infections caused by Candida or Cryptococcus
  • Nystatin (Mycostatin, Nilstat) (oral)
    • Used for the treatment of intestinal candidiasis; also available in a number of topical preparations

Voriconazole & Terbinafine

  • Newer agents
  • Voriconazole (Vfend)
    • Available in oral and IV forms
    • Treats invasive aspergillosis and serious infections caused by Scedosporium apiospermum and Fusarium species
  • Terbinafine (Lamisil)
    • Blocks the formation of ergosterol
    • Inhibits a CYP2D6 enzyme system
    • Oral drug for the treatment of onychomycosis of the toenail or fingernail

Azoles

  • Newer class of drugs used to treat systemic fungal infections
  • Less toxic than amphotericin B
  • Less effective than amphotericin B

Ketoconazole (Nizoral)

  • Used orally to treat many of the same mycoses as amphotericin B
  • Works by blocking the activity of a steroid in the fungal wall
  • Has side effect of blocking the activity of human steroids, including testosterone and cortisol
  • Pharmacokinetics: absorbed from the GI tract, metabolized in the liver, excreted in the feces
  • Contraindications: not drug of choice for patients with endocrine or fertility problems
  • Adverse reaction: hepatic toxicity
  • Drug-to-drug interactions: many

Fluconazole (Diflucan)

  • Not associated with the endocrine problems seen with ketoconazole
  • Used to treat candidiasis, cryptococcal meningitis, and other systemic fungal infections
  • Prophylactic agent for reducing the incidence of candidiasis in bone marrow transplant recipients
  • Pharmacokinetics: available in oral and IV preparations, excreted unchanged in the urine
  • Contraindications: renal dysfunction
  • Adverse reactions:
  • Drug-to-drug interactions: inhibits CYP450 and may be associated with drug-to-drug interactions

Itraconazole (Sporanox)

  • An oral agent used for the treatment of assorted systemic mycoses
  • Associated with hepatic failure
  • Slowly absorbed from the GI tract, it is metabolized in the liver by the CYP450 system
  • Excreted in the urine and feces

Sites of Action of Antifungal Agents

Sites of Action of Antifungal Agents

Sites of Action of Antifungal Agents

Overall Contraindications to Systemic Antifungal Agents

  • Anyone with a known allergy
  • Pregnant or lactating women (with the exception of terbinafine for life-threatening infections)
  • Patients with renal or liver disease
    • Drug metabolism or excretion may be altered, or condition may worsen as a result of the actions of the drug

Overall Adverse Reactions to Systemic Antifungal Agents

  • CNS effects
    • Headache, dizziness, fever, shaking, and chills
  • GI effects
    • Nausea, vomiting, dyspepsia, and anorexia
  • Hepatic dysfunction
  • Dermatologic effects
    • Rash and pruritus associated with local irritation
  • Renal dysfunction

Topical Antifungal Infections

  • Caused by dermatophytes
  • Tinea infections (ringworm)
    • Athlete‚Äôs foot (tinea pedis)
    • Jock itch (tinea cruris)
  • Candida
    • Yeast infections of the mouth and vagina

Topical Antifungal Agents

  • Action
    • Work to alter the cell permeability of the fungus, causing prevention of replication and fungal death
  • Indication
    • Indicated only for local treatment of mycoses, including tinea infection
  • Contraindication/caution
    • Limited to known allergy to any antifungal agent
  • Adverse effects
    • Local effects include irritation, burning, rash, and swelling
    • When taken as a suppository or troche, nausea, vomiting, hepatic dysfunction, urinary frequency, burning, and change in sexual activity can occur
  • Drug-to-drug interactions
    • None reported

Prototype Antifungal Agent

Fluconazole

Fluconazole

Clotrimazole

Clotrimazole

Use of Antifungals Across the Lifespan

Drug Therapy Across the Lifespan

Drug Therapy Across the Lifespan

Nursing Considerations for Systemic Antifungal Agents

  • Assessment (history and physical exam)
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations for Topical Antifungal Agents

  • Assessment (history and physical exam)
  • Nursing diagnosis
  • Implementation
  • Evaluation
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