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Drugs used to treat infections caused by fungi
Systemic Topical
Very large and diverse group of microorganismsBroken down into yeasts and molds
Fungal infections also known as mycoses
Some fungi are part of the normal flora of the skin, mouth, intestines, vagina
Reproduce by budding Can be used for
BakingAlcoholic beverages
Multicellular
Characterized by long, branching filaments called hyphae
Four general types Cutaneous Subcutaneous Superficial Systemic*
*Can be life threatening
*Usually occur in immunocompromised host
Candida albicans Due to antibiotic therapy, antineoplastics,
or immunosuppressants (corticosteroids) May result in overgrowth and systemic infections Growth in the mouth is called thrush or oral
candidiasis Common in newborn infants and
immunocompromised patients
Vaginal candidiasis “Yeast infection” Pregnancy, women with diabetes mellitus, women
taking oral contraceptives
Systemic amphotericin B, caspofungin, fluconazole,
ketoconazole, others
Topical Examples: clotrimazole, miconazole, nystatin
Major groups based on their mechanisms of action
Polyenes: amphotericin B and nystatin Imidazoles: ketoconazole (Nizoral) Triazoles: fluconazole (Diflucan), itraconazole
(Sporanox) Echinocandins: caspofungin (Cancidas), micafungin Listed individually, not by mechanism of action:
griseofulvin, flucytosine
Polyenes: amphotericin B and nystatin
Bind to sterols in cell membrane lining
Result: fungal cell death
Do not bind to human cell membranes or kill human cells
Use: Serious systemic fungal infections Administered: IV, PO, topical
Flucytosine (Ancobon)
Also known as 5-fluorocytosine (antimetabolite)
Taken up by fungal cells and interferes with DNA synthesis
Result: fungal cell death
Use: Systemic mycoses due to Candida species or Cryptococcus neoformans – administered orally
Imidazoles and triazoles:
Ketoconazole (Nizoral), fluconazole (Diflucan)
Inhibit fungal cell cytochrome P-450 enzymes, resulting in cell membrane leaking
Lead to altered cell membrane
Result: fungal cell death
Use: Ketoconazol (Nizoral): (po/topical): candidiasis, histoplasmosis, coccidoidomycosis; cutaneous candidiasis; tinea infections
Use: fluconazole (Diflucan): (po/IV): systemic, oral, esophageal or vaginal candidiasis; prevention of candidiasis after bone marrow transplant; cryptococcal meningitis.
griseofulvin
Disrupts cell division
Result: inhibited fungal mitosis (reproduction)
Use: (po) Dermatophytosis (skin, hair, nails)
Echinocandins: capsofungin (Cancidas)
Prevent the synthesis of glucans, which are essential components of fungal cell walls
Causes fungal cell death
Use: (IV) Invasive aspergillosis, Candidiasis
Systemic and topical fungal infections
Drug of choice for the treatment of many severe systemic fungal infections is amphotericin B
Choice of drug depends on type and location of infection
Fever / Headache Malaise Hypotension Muscle and joint pain Lowered potassium and magnesium levels Main concerns:
*Renal toxicity*Neurotoxicity: seizures and paresthesias
Many other adverse effects
Chills Dysrhythmias Nausea Anorexia
Fluconazole (Diflucan)
Nausea, vomiting, diarrhea, stomach pain, increased liver function studies
Flucytosine (Ancobon)
Nausea, vomiting, anorexia, headache, dizziness, others
griseofulvin
Rash, urticaria, headache, nausea, vomiting, anorexia, others
Liver failure
Renal failure
Porphyria: genetic disorder-erythrocyte formation/liver dysfunction (griseofulvin)
Many antifungal drugs are metabolized by the cytochrome P-450 enzyme system
Co administration of two drugs that are metabolized by this system may result in competition for these enzymes, and thus higher levels of one of the drugs
Before beginning therapy, assess for hypersensitivity, contraindications, and conditions that require cautious use
Obtain baseline VS, CBC, liver and renal function studies, and EKG
Assess for other medications used (prescribed and OTC) in order to avoid drug interactions
Follow manufacturer’s directions reconstitution and administration
Monitor VS of patients receiving IV infusions every 15 to 30 minutes
During IV infusions, monitor I&O to identify adverse effects
amphotericin B
To reduce the severity of the infusion-related reactions, pretreatment with an antipyretic (acetaminophen), antihistamines, antiemetics, and corticosteroid may be given
Use IV infusion pumps and the most distal veins possible
Some oral forms should be given with meals to decrease GI upset; others require an empty stomach—be sure to check
Nystatin given as an oral lozenge should be slowly and completely dissolved in the mouth (not chewed or swallowed whole)
Nystatin suspension should be swished thoroughly in the mouth as long as possible before swallowing
Monitor for therapeutic effectsEasing of the symptoms of infection Improved energy levelsNormal vital signs, including temperature
Monitor carefully for adverse effects