Antifungal Agents Chapter 11

How Fungus Differs from Bacteria 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 A culture should be obtained prior to prescribing anti-fungal agents. Patients on antifungal agents are typically immunosuppressed.

Amphotericin B Indications Aspergillosis the use is reserved for Leishmaniasis progressive, potential Cryptococcosis fatal infections due to Blastomycosis many adverse effects Moniliasis Coccidioidomycosis Histoplasmosis Mucormycosis Candida infections (topically)

Amphotericin B Indications - Progressive potential fatal fungal infections Pharmacokinetics - IV form, excreted in the urine Contraindications - 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 and Terbinafine Newer Agents Voriconazole (Vfend) Available in oral and IV forms Treats invasive aspergillosis and serious infections caused by Scedosporium apiospermum, or Fuscariium 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

Question Please answer the following statement as true or false. Nystatin, taken orally, is used for the treatment of intestinal candidiasis.

Rationale: Nystatin (Mycostatin, Nilstat) (Oral) Answer True Rationale: Nystatin (Mycostatin, Nilstat) (Oral) Used for the treatment of intestinal candidiasis; also available as a topical preparation.

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

Ketoconazole (Nizoral) (cont.) 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 Reactions – Hepatic toxicity Drug-Drug Interactions – Many (ex: digoxin, warfarin, CCB, antacids, fentanyl)

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

Fluconazole (Diflucan) (cont.) Pharmacokinetics - Available in oral and IV preparations, excreted unchanged in the urine. Contraindications – Renal dysfunction Adverse Reactions – Liver or renal toxicity Drug-Drug Interactions – Inhibits CYP450 may be associated with drug–drug interactions

Itraconazole (Sporanox) An oral agent used for the treatment of assorted systemic mycoses Associated with hepatic failure Is slowly absorbed from the GI tract and is metabolized in the liver by the CYP450 system Is excreted in the urine and feces

Site of Action of Antifungals

Overall Contraindications to Systemic Antifungal Agents Patient’s with a known allergy Pregnant or lactating women (with the exception of terbinafine for life-threatening infections) Patients with renal or liver disease May alter drug metabolism and excretion. Condition may worsen as a result of drug actions.

Overall Adverse Reactions to Systemic Antifungal Agents CNS Effects Headache, dizziness, fever, shaking, chills GI Effects Nausea, vomiting, dyspepsia, anorexia Hepatic Dysfunction Dermatological Effects Rash and pruritus associated with local irritation Renal Dysfunction

Question Which of the following is considered a contraindication of Ketoconazole ? A. Patients with renal problems B. Patients with fertility problems C. Patients with hepatic problems D. Patients with GI problems

B. Patients with fertility problems Answer B. Patients with fertility problems Rationale: Contraindications – not drug of choice for patients with endocrine or fertility problems.

Topical Antifungal Infections Caused by dermatophytes Tinea Infections (Ringworm) Athlete’s foot (tinea pedis) Jock itch (tinea cruris) Candida Yeast infections of the mouth and vagina

Topical Antifungal Agents (cont.) Action/Indication Work to alter the cell permeability of the fungus, causing prevention of replication and fungal death Indicated only for local treatment of mycoses, including tinea infections Contraindication/Cautions Limited to known allergy to any of these drugs

Topical Antifungal Agents (cont.) Adverse Effects Local effects include irritation, burning, rash, and swelling When taken as a suppository or troche: nausea, vomiting, hepatic dysfunction, urinary frequency and burning, and change in sexual activity Drug-to-Drug Interactions No reported drug–drug interactions

Prototype Antifungal Agent

Prototype Antifungal Agent

Prototype Antifungal Agent (Continued)

Use of Antifungals Across the Life Span

Nursing Considerations for Systemic Antifungal Agents Assessment: History and Physical Exam Nursing Diagnosis-page 169 (Acute pain r/t GI, CNS, and local effects of the drug; Disturbed Sensory Perception r/t CNS effects) Implementation-page 169 (appropriate C&S tests prior to beginning therapy, administer entire course of drug-could take as long as 6 months, monitor renal and hepatic function, freq small meals…) Evaluation-page 170 (monitor response to therapy, monitor for adverse effects)

Nursing Considerations for Topical Antifungal Agents Assessment: History and Physical Exam-page 172 (assess for known allergies, complete physical assessment, perform C&S) Nursing Diagnosis-Page 173 (Acute pain r/t local effects of the drug, knowledge deficit regarding drug therapy) Implementation-page 173-174 (culture effected area before beginning therapy to identify the causative fungus, ensure patient take the complete course of the drug regimen...) Evaluation-page 174 (monitor patient reponse to the drug, monitor for adverse effects, monitor effectiveness of teaching plan...)

Question The nurse is caring for a patient with a fungal infection. Which of the following would be considered an adverse effect of an antifungal medication? A. Burning or irritation in the sexual partner B. Abnormal kidney function tests C. Upper abdominal pain D. Urinary retention

Answer A. Burning or irritation in the sexual partner Rationale: Adverse effects: Troche: nausea, vomiting, abnormal liver function tests; topical: stinging, redness, urticaria, edema; vaginal: lower abdominal pain, urinary frequency, burning or irritation in the sexual partner