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Chapter 42
Antifungal Drugs
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Fungi
Very large and diverse group of microorganisms, including yeasts and molds
Fungal infections also known as mycoses
Some fungi are part of the normal flora of the skin, mouth, intestines, and vagina.
Systemic, cutaneous, subcutaneous, and superficial
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Fungi (Cont.)
Cutaneous, subcutaneous, and superficial: infections of various layers of the integumentary system (skin, hair, or nails)
Fungi that cause integumentary infections are known as dermatophytes.
Dermatomycoses
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Yeasts
Single-cell fungi
Reproduce by budding
Can be used for:
Baking
Alcoholic beverages
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Molds
Multicellular
Characterized by long, branching filaments called hyphae
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Mycotic Infections
Four general types:
Cutaneous
Subcutaneous
Superficial
Systemic
Can be life threatening
Usually occur in immunocompromised host
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7. Mycotic Infections (Cont.)
Candida albicans
May follow 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
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8. Mycotic Infections (Cont.)
Vaginal candidiasis
Yeast infection
Pregnancy, women with diabetes mellitus, women taking oral contraceptives
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9. Audience Response System Question
A patient has developed an aspergillosis infection. Which tissue does the aspergillosis affect?
Skin
Nails
Blood
Lungs
Correct answer: D
Rationale: The primary tissue affected by aspergillosis is the lungs.
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Antifungal Drugs
Drugs used to treat infections caused by fungi
Systemic
Amphotericin B, caspofungin, fluconazole, flucytosine, griseofulvin, itraconazole, ketoconazole, micafungin, nystatin, terbinafine, posaconazole, anidulafungin, and voriconazole.
Topical
Ophthalmic: natamycin
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11. Antifungal Drugs (Cont.)
Broken down into major groups based on their chemical structure
Synthetic triazoles: fluconazole, itraconazole, voriconazole
Echinocandins: caspofungin
Synthetic allylamine: terbinafine
Polyenes: amphotericin B, Amphotec (B), Abelcet (B), AmBisome (B), nystatin
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Mechanism of Action
Flucytosine
Also known as 5-fluorocytosine (5-FC), (antimetabolite)
Taken up by fungal cells and interferes with DNA synthesis
Result: fungal cell death
Older drug; newer drugs are more commonly used
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13. Mechanism of Action (Cont.)
Griseofulvin
Disrupts cell division
Result: inhibited fungal mitosis (cell division)
Older drug; newer drugs are more commonly used
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14. Mechanism of Action (Cont.)
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
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15. Mechanism of Action (Cont.)
Imidazoles and triazoles: ketoconazole, fluconazole, itraconazole, voriconazole
Inhibit fungal cell cytochrome P-450 enzymes, resulting in cell membrane leaking
Result: altered cellular metabolism and fungal cell death
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16. Mechanism of Action (Cont.)
Echinocandins: caspofungin, micafungin, and anidulafungin
Prevent the synthesis of glucans (essential components of fungal cell walls)
Result: fungal cell death
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Indications
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
Fluconazole: passes into the cerebrospinal fluid and inhibit the growth of cryptococcal fungi, effective in the treatment of cryptococcal meningitis
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18. Audience Response System Question
A patient is diagnosed with onychomycosis. The nurse anticipates use of which medication for the treatment of this condition?
terbinafine (Lamisil)
voriconazole (Vfend)
fluconazole (Diflucan)
amphotericin B (Amphocin, Fungizone)
Correct answer: A
Rationale: Terbinafine (Lamisil) is indicated for the treatment of onychomycosis (fungal infection of fingernail or toenail). Voriconazole (Vfend) is indicated for the treatment of invasive aspergillosis and other major fungal infections in patients who do not tolerate or respond to other antifungal drugs. Fluconazole (Diflucan) is indicated for the treatment of vaginal candidiasis, oropharyngeal and esophageal candidiasis, systemic candidiasis, and cryptococcal meningitis. Amphotericin B (Amphocin, Fungizone) is indicated for the treatment of systemic infections with broad spectrum of fungi. 
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19. Antifungal Drugs: Contraindications
Most common: drug allergy, liver failure, kidney failure, and porphyria (for griseofulvin)
Itraconazole: contraindicated treatment of onychomycoses in patients with severe cardiac problems
Voriconazole can cause fetal harm in pregnant women.
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20. Antifungal Drugs: Adverse Effects
Cardiovascular
Cardiac dysrhythmias
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21. Amphotericin B: Adverse Effects
Cardiac dysrhythmias
Neurotoxicity; tinnitus; visual disturbances; hand or feet numbness, tingling, or pain; convulsions
Renal toxicity, potassium loss, hypomagnesemia
Pulmonary infiltrates
Fever, chills, headache, nausea, occasional hypotension, gastrointestinal (GI) upset, anemia
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22. Amphotericin B: Adverse Effects: Prevention
Prescribers commonly order various premedications: antiemetics, antihistamines, antipyretics, and corticosteroids
Prevent or minimize infusion-related reactions to amphotericin B
Likelihood of such reactions can also be reduced by using longer-than-average drug infusion times (i.e., 2 to 6 hours)
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23. Audience Response System Question
A patient is receiving amphotericin B lipid complex. The nurse knows that an advantage of the lipid formulations of this drug is that they:
have a lower cost.
can be administered quickly.
take longer to be absorbed.
cause fewer adverse effects.
Correct answer: D
Rationale: Lipid formulations of amphotericin B have been developed in an attempt to decrease the incidence of its adverse effects and increase its efficacy. There are currently three lipid preparations of amphotericin B: (1) amphotericin B lipid complex (Abelcet), (2) amphotericin B cholesteryl complex (Amphotec), and (3) liposomal amphotericin B (AmBisome). These lipid dosage forms have a much higher cost than conventional amphotericin B and for this reason are often used only when patients are intolerant of or have an infection refractory to nonlipid amphotericin B.
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24. Antifungal Drugs: Adverse Effects
Fluconazole
Nausea, vomiting, diarrhea, stomach pain,
Increased liver enzymes
Use with caution in patients with renal and liver dysfunction
Nystatin
Nausea, vomiting, anorexia, diarrhea, rash
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25. Antifungal Drugs: Contraindications
Liver failure
Renal failure
Porphyria (griseofulvin)
Drug allergy
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26. Antifungal Drugs: Interactions
Many antifungal drugs are metabolized by the cytochrome P-450 enzyme system.
Coadministration 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.
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Nursing Implications
Before beginning therapy, assess for hypersensitivity, possible contraindications, and conditions that require cautious use.
Obtain baseline vital signs, complete blood count, liver and renal function studies, and electrocardiography.
Assess for other medications used (prescribed and over the counter) to avoid drug interactions.
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28. Nursing Implications (Cont.)
Follow the manufacturer’s directions carefully for reconstitution and administration.
Monitor vital signs of patients receiving intravenous (IV) infusions every 15 to 30 minutes.
During IV infusions, monitor input and output to identify adverse effects.
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29. Audience Response System Question
Fifteen minutes after an infusion of amphotericin B was started, the patient begins to complain of fever, chills, muscle pain, and nausea. His heart rate has increased slightly, but his blood pressure is down to 100/68 mm Hg. What is the nurse’s priority?
Notify the prescriber immediately.
Recognize an impending anaphylactic reaction and stop the infusion.
Assess for other symptoms of this expected infusion-related reaction.
Slow the infusion to reduce these adverse effects.
Correct answer: C
Rationale: Almost all patients who receive amphotericin B experience fever, chills, hypotension, tachycardia, malaise, muscle and joint pain, anorexia, nausea and vomiting, and headache. For this reason, antihistamines, acetaminophen (an antipyretic), and antiemetics may be given as pretreatment to reduce these expected effects.
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30. Nursing Implications (Cont.)
Amphotericin B
To reduce the severity of the infusion-related reactions, pretreatment with an antipyretic (acetaminophen), antihistamines, antiemetics, and corticosteroids may be given.
Use IV infusion pumps and the most distal veins possible.
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31. Nursing Implications (Cont.)
Some oral forms should be given with meals to decrease GI upset; others require an empty stomach—be sure to check.
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32. Audience Response System Question
A patient is taking nystatin (Mycostatin) in an oral troche form for oral candidiasis. Which instruction is correct?
Allow the troche to dissolve slowly in the mouth.
Swish the medication in the mouth and then swallow it.
Chew the troche thoroughly to activate the medication.
Swallow the troche whole without chewing.
Correct answer: A
Rationale: Oral troche or lozenge forms of this medication should be allowed to dissolve slowly in the mouth without chewing.
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33. Nursing Implications (Cont.)
Nystatin given as an oral lozenge or troche 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.
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34. Nursing Implications (Cont.)
Monitor for therapeutic effects.
Easing of symptoms of infection
Improved energy levels
Normal vital signs, including temperature
Monitor carefully for adverse effects.
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