Chapter 42 Antifungal Drugs Copyright 2017 Elsevier Inc

Chapter 42 Antifungal Drugs Copyright © 2017, Elsevier Inc. All rights reserved.

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 Copyright © 2017, Elsevier Inc. All rights reserved. 2

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 Copyright © 2017, Elsevier Inc. All rights reserved. 3

Yeasts Single-cell fungi Reproduce by budding Can be used for: Baking Ø Alcoholic beverages Ø Copyright © 2017, Elsevier Inc. All rights reserved. 4

Molds Multicellular Characterized by long, branching filaments called hyphae Copyright © 2017, Elsevier Inc. All rights reserved. 5

Mycotic Infections Four general types: Cutaneous Ø Subcutaneous Ø Superficial Ø Systemic • Can be life threatening • Usually occur in immunocompromised host Ø Copyright © 2017, Elsevier Inc. All rights reserved. 6

Mycotic Infections (Cont. ) Candida albicans May follow antibiotic therapy, antineoplastics, or immunosuppressants (corticosteroids) Ø May result in overgrowth and systemic infections Ø Growth in the mouth is called thrush or oral candidiasis Ø Common in newborn infants and immunocompromised patients Ø Copyright © 2017, Elsevier Inc. All rights reserved. 7

Mycotic Infections (Cont. ) Vaginal candidiasis Yeast infection Ø Pregnancy, women with diabetes mellitus, women taking oral contraceptives Ø Copyright © 2017, Elsevier Inc. All rights reserved. 8

Audience Response System Question A patient has developed an aspergillosis infection. Which tissue does the aspergillosis affect? A. B. C. D. Skin Nails Blood Lungs Copyright © 2017, Elsevier Inc. All rights reserved. 9

Antifungal Drugs used to treat infections caused by fungi Systemic Ø Amphotericin B, caspofungin, fluconazole, flucytosine, griseofulvin, itraconazole, ketoconazole, micafungin, nystatin, terbinafine, posaconazole, anidulafungin, and voriconazole. Topical Ophthalmic: natamycin Copyright © 2017, Elsevier Inc. All rights reserved. 10

Antifungal Drugs (Cont. ) Broken down into major groups based on their chemical structure Synthetic triazoles: fluconazole, itraconazole, voriconazole Ø Echinocandins: caspofungin Ø Synthetic allylamine: terbinafine Ø Polyenes: amphotericin B, Amphotec (B), Abelcet (B), Am. Bisome (B), nystatin Ø Copyright © 2017, Elsevier Inc. All rights reserved. 11

Mechanism of Action Flucytosine Also known as 5 -fluorocytosine (5 -FC), (antimetabolite) Ø Taken up by fungal cells and interferes with DNA synthesis Ø Result: fungal cell death Ø Older drug; newer drugs are more commonly used Ø Copyright © 2017, Elsevier Inc. All rights reserved. 12

Mechanism of Action (Cont. ) Griseofulvin Disrupts cell division Ø Result: inhibited fungal mitosis (cell division) Ø Older drug; newer drugs are more commonly used Ø Copyright © 2017, Elsevier Inc. All rights reserved. 13

Mechanism of Action (Cont. ) Polyenes: amphotericin B and nystatin Bind to sterols in cell membrane lining Ø Result: fungal cell death Ø Do not bind to human cell membranes or kill human cells Ø Copyright © 2017, Elsevier Inc. All rights reserved. 14

Mechanism of Action (Cont. ) Imidazoles and triazoles: ketoconazole, fluconazole, itraconazole, voriconazole Inhibit fungal cell cytochrome P-450 enzymes, resulting in cell membrane leaking Ø Result: altered cellular metabolism and fungal cell death Ø Copyright © 2017, Elsevier Inc. All rights reserved. 15

Mechanism of Action (Cont. ) Echinocandins: caspofungin, micafungin, and anidulafungin Prevent the synthesis of glucans (essential components of fungal cell walls) Ø Result: fungal cell death Ø Copyright © 2017, Elsevier Inc. All rights reserved. 16

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 Copyright © 2017, Elsevier Inc. All rights reserved. 17

Audience Response System Question A patient is diagnosed with onychomycosis. The nurse anticipates use of which medication for the treatment of this condition? A. terbinafine (Lamisil) B. voriconazole (Vfend) C. fluconazole (Diflucan) D. amphotericin B (Amphocin, Fungizone) Copyright © 2017, Elsevier Inc. All rights reserved. 18

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. Copyright © 2017, Elsevier Inc. All rights reserved. 19

Antifungal Drugs: Adverse Effects Cardiovascular Cardiac dysrhythmias Copyright © 2017, Elsevier Inc. All rights reserved. 20

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 Copyright © 2017, Elsevier Inc. All rights reserved. 21

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) Copyright © 2017, Elsevier Inc. All rights reserved. 22

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: A. have a lower cost. B. can be administered quickly. C. take longer to be absorbed. D. cause fewer adverse effects. Copyright © 2017, Elsevier Inc. All rights reserved. 23

Antifungal Drugs: Adverse Effects Fluconazole Nausea, vomiting, diarrhea, stomach pain, Ø Increased liver enzymes Ø Use with caution in patients with renal and liver dysfunction Ø Nystatin Ø Nausea, vomiting, anorexia, diarrhea, rash Copyright © 2017, Elsevier Inc. All rights reserved. 24

Antifungal Drugs: Contraindications Liver failure Renal failure Porphyria (griseofulvin) Drug allergy Copyright © 2017, Elsevier Inc. All rights reserved. 25

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. Copyright © 2017, Elsevier Inc. All rights reserved. 26

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. Copyright © 2017, Elsevier Inc. All rights reserved. 27

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. Copyright © 2017, Elsevier Inc. All rights reserved. 28

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? A. Notify the prescriber immediately. B. Recognize an impending anaphylactic reaction and stop the infusion. C. Assess for other symptoms of this expected infusionrelated reaction. D. Slow the infusion to reduce these adverse effects. Copyright © 2017, Elsevier Inc. All rights reserved. 29

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. Ø Use IV infusion pumps and the most distal veins possible. Ø Copyright © 2017, Elsevier Inc. All rights reserved. 30

Nursing Implications (Cont. ) Some oral forms should be given with meals to decrease GI upset; others require an empty stomach—be sure to check. Copyright © 2017, Elsevier Inc. All rights reserved. 31

Audience Response System Question A patient is taking nystatin (Mycostatin) in an oral troche form for oral candidiasis. Which instruction is correct? A. B. C. D. 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. Copyright © 2017, Elsevier Inc. All rights reserved. 32

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. Copyright © 2017, Elsevier Inc. All rights reserved. 33

Nursing Implications (Cont. ) Monitor for therapeutic effects. Easing of symptoms of infection Ø Improved energy levels Ø Normal vital signs, including temperature Ø Monitor carefully for adverse effects. Copyright © 2017, Elsevier Inc. All rights reserved. 34