antifungal p.1

Amphotericin B: A Polyene Antifungal Agent

• Category: Polyene Antifungal Agent
• Primary Function: Effective against a wide range of fungal infections, it's the go-to treatment for many systemic fungal infections.
• Unique Feature: It targets ergosterol, a key component of fungal cell membranes. Bacteria lack sterols, making this drug ineffective against bacterial infections.

Mechanism of Action

• Amphotericin B binds to the fungal cell membrane, increasing its permeability.
• This causes leakage of intracellular contents, reducing the viability of the fungus.
• The action can be fungistatic (inhibits growth) or fungicidal (kills the fungus), depending on the drug concentration and fungal susceptibility.

Indications and Therapeutic Uses

• Systemic Fungal Infections: A mainstay treatment for most systemic fungal infections.

Side Effects and Adverse Reactions

• Infusion Reactions: Common during infusion due to the release of inflammatory chemicals. Symptoms include fever, chills, nausea, and headache. Pretreatment with antihistamines and pain relievers can help. Infusion site problems like inflammation can also occur.
• Nephrotoxicity: A common side effect, especially with high doses (over 4 grams).
• Hypokalemia: Low potassium levels are a risk for individuals with kidney problems who use amphotericin B.
• Hematologic Effects: Can increase the risk of bone marrow suppression, potentially leading to anemia.
• Intrathecal Injection Reactions: Intrathecal (spinal) administration can cause nausea, vomiting, headache, and pain in the back, legs, and abdomen. Serious reactions like vision problems, hearing loss, and numbness are rare.

Precautions

• Dosage needs to be reduced for individuals with kidney problems.
• Due to the risk of toxicity, it should be used for the shortest time possible. Treatment typically lasts 6-8 weeks but might need to continue for 3-4 months.

Contraindications

• Not for individuals with severe kidney problems.

Black Box Warning

• Because of toxicity, amphotericin B should only be used for infections that are potentially life-threatening.

Drug Interactions

• Nephrotoxic Agents: Using amphotericin B with other nephrotoxic drugs (drugs harmful to the kidneys) like aminoglycosides, cyclosporine, or NSAIDs can increase the risk of kidney damage.
• Flucytosine: Amphotericin B enhances the antifungal effects of flucytosine, possibly allowing lower doses of amphotericin B to be used.

Dosing, Administration, & Client Teaching

• Dosing: Varies based on infection type, severity, and individual response. Dosage guidelines are used to determine specific doses. Initial test doses are used to assess individual reactions.
• Formulations:
  • Comes in conventional and three lipid-based formulations.
  • Lipid-based formulations are equally effective but are more expensive and cause less toxicity.
• Administration: Given intravenously, daily or every other day for several months.
• Client Teaching: Clients should be informed about potential side effects and how to report them.

Labs to Monitor:

• Basic Metabolic Panel: Monitor kidney function (BUN, creatinine, creatinine clearance) and electrolyte levels (potassium, magnesium) regularly.
• Complete Blood Count (CBC): Monitor for anemia.

Amphotericin B (Abelcet)

• Polyene antifungal agent, effective against a broad spectrum of fungi, considered the drug of choice for most systemic mycoses.
• Mechanism of action: binds to ergosterol in fungal cell membrane, increasing permeability, leading to intracellular leakage, reducing organism viability.
• Fungistatic or fungicidal activity depending on concentration and fungal susceptibility.

Indications and Therapeutic Uses

• Primarily for systemic fungal infections, including those caused by Candida, Aspergillus, Cryptococcus, and Histoplasma.

Side Effects and Adverse Reactions

• Infusion reactions: fever, chills, rigors, nausea, headache, and phlebitis. Consider diphenhydramine and acetaminophen pre-treatment for mild reactions.
• Nephrotoxicity: common adverse effect, dose-dependent. Renal impairment likely with doses exceeding 4g.
• Hypokalemia: risk for clients with renal impairment.
• Hematologic effects: bone marrow suppression, leading to anemia.
• Intrathecal injection reactions: nausea, vomiting, headache, back pain, leg pain, abdominal pain, visual disturbances, hearing impairment and paresthesia.

Precautions and Contraindications

• Reduce dosage in clients with renal impairment.
• Administer for shortest duration possible, typically 6-8 weeks, extending to 3-4 months if required.
• Contraindicated in clients with severe renal impairment.

Black Box Warning

• Amphotericin B should only be used for life-threatening infections due to its toxicity.

Drug Interactions

• Nephrotoxic agents: increased risk of renal damage when used concurrently (aminoglycosides, cyclosporine, NSAIDs).
• Flucytosine: potentiates antifungal action, requiring reduced amphotericin B dosage, leading to enhanced treatment and reduced toxicity.

Dosing, Administration, & Client Teaching

• Dosing is individualized based on condition, severity, and client response.
• Consult drug dosing guidelines for personalized regimen.
• Initial test dose recommended to assess client reaction.
• Available in four formulations: conventional and three lipid-based (more costly, less toxic).
• All formulations are administered intravenously, daily or every other day for several months.

Client Teaching

• Educate clients on potential adverse effects and importance of reporting them.

Labs to Monitor

• Basic Metabolic Panel: monitor BUN, creatinine, creatinine clearance, potassium and magnesium on initiation and every 3-4 days.
• Complete Blood Count (CBC): monitor for anemia on initiation and every 3-4 days.

Amphotericin B (Abelcet)

• Polyene antifungal agent, effective against a broad spectrum of pathogenic fungi
• Mechanism of action: Binds to ergosterol in fungal cell membranes, increasing permeability, leading to intracellular leakage and reduced viability
• Fungistatic or fungicidal depending on concentration and fungal susceptibility
• Indications: Drug of choice for most systemic mycoses
• Adverse effects:
  • Infusion reactions: Fever, chills, rigors, nausea, headache, phlebitis
  • Nephrotoxicity: Dose-dependent, likely with doses exceeding 4g
  • Hypokalemia: Risk in clients with renal impairment
  • Hematologic effects: Increased risk of bone marrow suppression, anemia
  • Intrathecal injection reactions: Nausea, vomiting, headache, back, leg, and abdominal pain; rare reactions include visual disturbances, hearing impairment, and paresthesia
• Precautions:
  • Reduce dosage in clients with renal impairment
  • Administer for the shortest time possible (6-8 weeks, but may last 3-4 months)
• Contraindications: Severe renal impairment
• Black box warning: Only for potentially life-threatening infections due to toxicity
• Drug interactions:
  • Increased risk of renal damage with nephrotoxic agents (aminoglycosides, cyclosporine, NSAIDs)
  • Potentiates antifungal action of flucytosine, requiring a reduction in amphotericin B dosage
• Dosing:
  • Varies based on condition, severity, and client response
  • Individualized based on disease severity and client tolerability
  • Initial test dose to assess client reaction
  • Four formulations: conventional and three lipid-based (as effective, more costly, less toxic)
  • IV administration daily or every other day for several months
• Client teaching: Educate on potential adverse effects and reporting
• Labs to monitor:
  • Basic metabolic panel: BUN, creatinine, creatinine clearance every 3-4 days; potassium and magnesium every 3-4 days
  • Complete blood count: Monitor for anemia every 3-4 days

Amphotericin B

• Amphotericin B is an antifungal medication, specifically a polyene antifungal agent.
• It's effective against a wide range of fungal infections and is often the preferred treatment for serious systemic fungal infections.
• Amphotericin B targets ergosterol, a component of fungal cell membranes. This makes it specific to fungi, as bacterial cell membranes lack sterols.
• The drug binds to ergosterol, increasing the permeability of the fungal cell membrane. This leads to leakage of intracellular contents, ultimately disrupting fungal viability.

Mechanism of Action

• Amphotericin B works by disrupting the fungal cell membrane.
• It binds to ergosterol in the fungal cell membrane, increasing its permeability.
• This results in leakage of essential intracellular components, hindering the fungal cell's ability to function.
• Depending on the concentration and fungal susceptibility, the action can be fungistatic (inhibiting fungal growth) or fungicidal (killing the fungi).

Indications

• Amphotericin B is primarily used to treat systemic fungal infections, meaning infections that have spread throughout the body.

Side Effects and Adverse Reactions

• Infusion Reactions: Fever, chills, nausea, and headache are common side effects. These reactions are often triggered by the release of proinflammatory cytokines. Diphenhydramine and acetaminophen can help manage these milder reactions. Phlebitis (inflammation of the veins) can occur. Heparin and infusing through a central vein can minimize this risk.
• Nephrotoxicity: Amphotericin B known for causing kidney damage, especially with prolonged use. The risk increases with higher doses.
• Hypokalemia: Low potassium levels are another side effect, particularly in clients with renal impairment.
• Hematologic Effects: Amphotericin B can suppress bone marrow function, leading to normocytic, normochromic anemia (a type of anemia with normal red blood cell size and color).
• Intrathecal Injection Reactions: If given intrathecally (direct injection into the spinal canal), it can cause nausea, vomiting, headache, back pain, leg pain, and abdominal pain. Rarer side effects include visual disturbances, hearing impairment, and a tingling sensation (paresthesia).

Precautions

• Dosage should be adjusted for clients with impaired kidney function.
• Due to its potential toxicity, Amphotericin B should be administered for the shortest possible duration. Treatment typically lasts 6-8 weeks, sometimes extending to 3-4 months.

Contraindications

• Individuals with severe renal impairment are not candidates for Amphotericin B therapy.
• Since this drug is potentially harmful, it is only used to treat life-threatening fungal infections, not milder ones.

Drug Interactions

• Amphotericin B should be used with caution alongside nephrotoxic drugs, such as aminoglycosides, cyclosporine, and NSAIDs, as they can increase the risk of kidney damage.
• Amphotericin B can potentiate (enhance) the antifungal effects of flucytosine, which means the dose of Amphotericin B may need to be reduced when combined with flucytosine.

Dosing and Administration

• Dosage varies depending on the specific condition, severity of the infection, and individual patient response.
• Consult drug dosing guidelines for customized dosing recommendations.
• Initial test doses are often administered to assess the patient’s reaction.
• Amphotericin B is available in several formulations: conventional and lipid-based formulations. Lipid-based formulations are generally more expensive but may cause fewer side effects.
• All formulations are administered intravenously (IV) and are typically given daily or every other day for extended periods (months).

Client Teaching

• Clients should be informed about potential side effects and advised to report any noticeable changes or concerns.

Lab Monitoring

• Monitor renal function (BUN, creatinine, creatinine clearance) at the start of therapy and every 3-4 days.
• Monitor potassium and magnesium levels at the start of therapy and every 3-4 days.
• Monitor complete blood count (CBC) for anemia at the start of therapy and every 3-4 days.