Antifungal therapy

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Which statement by Mr. Winter indicates an accurate understanding about fluconazole?

"I can take the drug with food." Fluconazole can be taken without regard to food.

A young adult woman is prescribed an antifungal for vulvovaginal infection. Which statement made by the patient indicates a need for more teaching?

"I will stop taking the drug while I am menstruating."

Fluconazole:Class, usual adult dosage, special considerations for administration

Azole PO: 100-400 mg daily Take without regard to food.

Even though many antifungals are well tolerated, side effects do exist. At higher doses, side effects are more common, and the risk for adverse reactions is increased. Renal and hepatic dysfunction increases the risk for adverse reactions.

Common side effects include chills, nausea, vomiting, and fever. More serious adverse effects include hypotension, paresthesia, nephrotoxicity, and hypokalemia. QT prolongation can occur when administered concurrently with other drugs that prolong QT interval. Injection site reaction, such as thrombophlebitis, can occur with IV drugs.

A patient on fluconazole should have which laboratory tests monitored frequently?

Creatinine Liver enzymes Serum potassium

Miscellaneous: Griseofulvin distribution

Crosses placenta

Miscellaneous: Griseofulvin mechanism of action

Depositing of griseofulvin in the keratin of precursor cells of skin, hair, and nails making the newly formed keratin resistant to fungal invasion

Echinocandins: Caspofungin mechanism of action

Disrupts the fungal cell wall, inhibiting the biosynthesis of essential component of the cell wall needed for some fungi; has narrow antifungal spectrum

Azoles: Fluconazole metabolism

Does not undergo first-pass metabolism

Antifungal Drugs contraindications

Drug allergy, serious renal and hepatic disease, and porphyria (manifested in neurologic symptoms or skin problems) are the most common contraindications for antifungal drugs. Fluconazole should not be administered concurrently with other drugs that prolong QT interval. Fluconazole and griseofulvin are contraindicated in pregnancy.

Class Antimetabolites examples

Flucytosine

Which patient condition would require the nurse to clarify a prescription for griseofulvin with the health care provider?

Systemic candida infection

Polyenes: Amphotericin B therapeutic use

Systemic mycoses

Amphotericin B is the preferred

antifungal drug for the treatment of systemic infections. It is a broad-spectrum antifungal that binds to the fungal cell membrane, increasing membrane permeability and thereby reducing viability of the fungus. Before the availability of amphotericin B, systemic fungal infections often were fatal. Amphotericin B is administered intravenously slowly in low doses. Treatment usually lasts 6 to 8 weeks; in some cases, treatment lasts several more months.

Antifungal drugs, such as amphotericin B and ketoconazole, are also referred to as

antimycotic drugs. Antifungal drugs are considered either fungistatic (inhibit the growth of the fungi) or fungicidal (kill the fungi), depending of the susceptibility of the fungus and the dose of the antifungal drug. Amphotericin B, used to treat systemic fungal infections, is administered intravenously only, whereas ketoconazole, used to treat systemic and local infections, may be taken orally.

Amphotericin B is primarily

protein bound and has a long half-life. Due to the severity of potential adverse drug effects, amphotericin B is generally given in the hospital.

Miscellaneous: Griseofulvin excretion

renal excretion, feces, perspiration

Azoles: Fluconazole peak

1-2hr

Azoles: Fluconazole distribution

11-12% protein bound

Polyenes: Amphotericin B half-life

15days

Antimetabolites: Flucytosine peak

2-6hrs

Azoles: Fluconazole half-life

20-50hr

Knowing that flucytosine is administered every 6 hours, which time frame describes the half-life of flucytosine?

3 to 8 hours The half-life of flucytosine is 3 to 8 hours and must be administered every 6 hours to maintain maximum drug effect.

Antimetabolites: Flucytosine half life

3-8hr

Miscellaneous: Griseofulvin half life

9-22hrs

Echinocandins: Caspofungin half-life

9-50hrs

Polyenes Amphotericin B distribution

90% protein bound

Echinocandins: Caspofungin distribution

97% protein bound

As the nurse prepares to administer a dose of amphotericin, redness and pain at the intravenous (IV) site are noted. Which action would be appropriate for the nurse to take?

Administer amphotericin B through a different IV site.

Antifungal Drugs general teachings

Advise patients to take the drug as prescribed. Compliance is of utmost importance to prevent a relapse of the infection. Instruct female patients being treated for vaginal infections to abstain from sexual intercourse until the infection is resolved. Also, instruct female patients to continue taking the drug while menstruating and notify the health care provider if symptoms persist after completing treatment. Encourage patients with local infections to keep affected body areas clean and dry and to wear light and cool clothing. Avoid contact of the topical dosage form with the eyes, mouth, nose, or other mucous membranes. Inform patients taking ketoconazole not to consume alcohol.

Miscellaneous: Griseofulvin absorption

Almost complete after oral (PO) administration Absorption enhanced with fatty food

Class Polyenes examples

Amphotericin B

Flucytosine: Class, usual adult dosage, special considerations for administration

Antimetabolite PO: 50-150 mg/kg/day divided q6hrDose adjustment may be necessary with renal impairment.

Echinocandins: Caspofungin therapeutic use

Aspergillus spp.Candida spp.

Flucytosine 37 mg/kg every 6 hours is prescribed to a patient with decreased urine output. Which action would the nurse anticipate?

Assess renal function.

By which mechanisms does amphotericin B induce its therapeutic effects

Binds to the fungal cell wall Increases the cell membrane permeability Causes fungal intracellular contents to leak out of the cell

Polyenes: Amphotericin B mechanism of action

Binds to the fungal cell wall membrane, increasing permeability and allowing leakage of intracellular contents

Azoles: Fluconazole therapeutic use

Canidida spp.

Class Echinocandins examples

Caspofungin Micafungin Anidulafungin

Which priority assessment would the nurse conduct in Mr. Winter before administering fluconazole?

Check renal and hepatic function. Before administering fluconazole, the nurse should assess renal and hepatic function. Diabetes and hypertension can damage renal arteries, leading to kidney failure. Fluconazole is contraindicated in persons with severe renal disease. Because fluconazole is metabolized by the liver, if administered to persons with hepatic dysfunction, hepatic toxicity can occur.

Caspofungin: Class, usual adult dosage, special considerations for administration

Echinocandins IV: 50 mg daily infused over 1 hr Do not mix with dextrose-containing solutions. Do not coadminister with other drugs .Mix gently. Infuse slowly over 1 hr.

Monitoring for potential adverse effects and evaluating the patient's response when administering antifungal medications are essential parts of nursing care.

Evaluate the effectiveness of the antifungal medications by monitoring for decreasing signs and symptoms of fungal infections (i.e., redness and pruritus). Observe for adverse drug effects, which may include nausea, vomiting, headache, and electrolyte imbalance. With IV administration, monitor IV site for signs of phlebitis. If phlebitis occurs, initiate a new IV site. Monitor renal and liver function tests.

Miscellaneous: Griseofulvin metabolism

Extensively metabolized by the liver

Which antifungal inhibits the formation of ergosterol, a major sterol in the fungal cell membrane?

Fluconazole Fluconazole inhibits the formation of ergosterol by interfering with the cytochrome P450 (CYP450) enzyme that is needed to convert lanosterol to ergosterol. Ergosterol is needed by the fungal cell wall.

The nurse is preparing to administer several antifungal drugs. Which antifungal drugs would the nurse anticipate administering orally?

Fluconazole Flucytosine Griseofulvin

Class Azoles examples

Fluconazole Itraconazole Ketoconazole

Class Miscellaneous antifungals

Griseofulvin

Azoles: Fluconazole mechanism of action

Inhibits cytochrome P450 (CYP450) enzyme that is needed by the fungal cells, interfering with the formation of a major sterol, ergosterol, in fungal cell membrane

For which reason is amphotericin B administered intravenously?

It is poorly absorbed through the gastrointestinal (GI) tract. Amphotericin B must be administered intravenously because it is poorly absorbed through the GI tract.

Miscellaneous: Griseofulvin therapeutic use

Local fungal infections, such as tineas and onychomycosis; is not effective against systemic mycoses

Antifungal Drugs, drugs interactions

Many antifungals inhibit hepatic drug-metabolizing enzymes and raise levels of other drugs, at times to a toxic level. Others are hepatic-metabolizing enzyme inducers, such as griseofulvin, which can decrease the effects of drugs, such as warfarin. Some antifungals are nephrotoxic and when administered with other nephrotoxic drugs can worsen the toxicity to the kidneys. Therefore it is important to monitor renal function.

Which of the antifungal drugs are classified as echinocandins?

Micafungin Micafungin is classified as an echinocandin. Caspofungin Caspofungin is classified as an echinocandin.

Antimetabolites: Flucytosine metabolism

Minimally hepatic

Griseofulvin: Class, usual adult dosage, special considerations for administration

Miscellaneous Dose dependent on types of tinea and drug formulation. PO: 250-1000 mg daily May need 2 wk to 6 mo of treatment. Drug absorption is enhanced with fatty foods.

Antifungal drugs treat serious systemic and local infections. These drugs have the potential for severe adverse effects, so patient assessment is essential before administration of these medications.

Obtain a medical history with special attention to severe renal or hepatic disease. Antifungal drugs, such as amphotericin B, fluconazole, flucytosine, and ketoconazole, are contraindicated in patients with severe kidney and liver disease. Assess for comorbidities that may suppress the immune system. Check laboratory tests for liver enzyme values, glomerular filtration rate (GFR), blood urea nitrogen (BUN), bilirubin, and serum creatinine. Use these test results for future comparison. Assess for previous treatment with antifungals. Obtain and record vital signs for future comparison.

Antimetabolites: Flucytosine mechanism of action

Once taken up by fungal cells, converts to 5-fluorouracil, a powerful metabolite which disrupts fungal DNA and RNA synthesis

Fungal infections can be opportunistic or nonopportunistic (pathogenic) and can be local or systemic in the body.

Opportunistic infections most often occur in those who are immunocompromised or immunosuppressed (those with uncontrolled diabetes, HIV, cancer, or transplant patients). They can also occur in those taking antibiotics, corticosteroids, chemotherapy, or immunosuppressant drugs. Candidiasis is an example of an opportunistic fungal infection that occurs in an immunocompromised state, resulting in an overgrowth of the fungus Candida spp., a normal flora (yeast) present in the mouth, skin, intestine, and vagina. Pathogenic infections, such as histoplasmosis, which is caused by breathing in spores of a fungus often found in bird droppings, can occur in a healthy individual.

Amphotericin B: Class, usual adult dosage, special considerations for administration

Polyenes Maintenance dose: Intravenous (IV): 0.25-1 mg/kg daily Test dose with 1 mg IV x 1 over 20-30 min, followed by loading dose of 0.25-0.5 mg/kg IV over 2-6 hr Dose adjusted for renal impairment Protect from light

Polyenes Amphotericin B absorption

Poorly absorbed through the gastrointestinal (GI) tract

Echinocandins: Caspofungin absorption

Poorly absorbed via GI tract

The nurse is about to administer fluconazole to a young adult for vulvovaginal fungal infection. Which priority assessment is needed?

Pregnancy test Fluconazole is contraindicated in pregnancy.

Azoles: Fluconazole absorption

Rapidly and almost completely absorbed by the GI tract

A patient receiving amphotericin B would be instructed to immediately report which adverse effect of the medication?

Ringing of the ears

Antimetabolites: Flucytosine therapeutic use

Serious infections due to susceptible strains of Candida and C. neoformans

Antifungal Drugs side effects

Teach patients to avoid operating hazardous equipment or a motor vehicle when taking amphotericin B, ketoconazole, or flucytosine, because these drugs may cause central nervous system (CNS) symptoms (visual changes, sleepiness, dizziness, and lethargy). Encourage patients to report all side and adverse effects (e.g., nausea, vomiting, diarrhea, dermatitis, rash, dizziness, tinnitus, edema, and flatulence). Some patients receiving amphotericin B may need long-term treatment (i.e., 2 weeks to possibly 3 months). The health care provider is to be notified immediately for bleeding, bruising, or soft tissue swelling at the IV site. Also, due to the length of treatment, all side and adverse effects should be reported (tinnitus, blurred vision, headache, rash, chills, and fever).

Antimetabolites: Flucytosine absorption

Well absorbed by the GI tract (75%-90%)

Antimetabolites: Flucytosine distribution

Well distributed with 2%-4% protein bound

Polyenes Amphotericin B metabolism

Unknown

Antimetabolites: Flucytosine excretion

Urine

Polyenes Amphotericin B excretion

Urine

Echinocandins: Caspofungin excretion

Urine (41%) and feces (35%)

Azoles: Fluconazole excretion

Urine (60%-80%)

Echinocandins: Caspofungin metabolism

Via hydrolysis

Amphotericin B infusion has been associated with

delirium, hemodynamic instability, wheezing, and hypoxia. Close monitoring is essential during treatment.

Antifungals are either

fungistatic or fungicidal depending on the susceptibility of the fungus and the dosage of antifungals. The miscellaneous antifungal, griseofulvin, is taken orally but treats only local fungal infections.

Antimetabolites: Flucytosine duration

unknown

Antimetabolites: Flucytosine onset

unknown

Azoles: Fluconazole duration

unknown

Azoles: Fluconazole onset

unknown

Echinocandins: Caspofungin duration

unknown

Echinocandins: Caspofungin onset

unknown

Echinocandins: Caspofungin peak

unknown

Miscellaneous: Griseofulvin duration

unknown

Miscellaneous: Griseofulvin onset

unknown

Miscellaneous: Griseofulvin peak

unknown

Polyenes: Amphotericin B duration

unknown

Polyenes: Amphotericin B onset

unknown

Polyenes: Amphotericin B peak

unknown


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