Mechanism Of Antifungal Drugs PDF

**Prototype: amphotericin b (Abelcet) ** - **Category**: Polyene Antifungal Agent  - **Primary Function**: Amphotericin B is active against a broad spectrum of pathogenic fungi and is the drug of choice for most systemic mycoses.  - **Unique Features:** Amphotericin B binds to the e...

**Prototype: amphotericin b (Abelcet) ** - **Category**: Polyene Antifungal Agent  - **Primary Function**: Amphotericin B is active against a broad spectrum of pathogenic fungi and is the drug of choice for most systemic mycoses.  - **Unique Features:** Amphotericin B binds to the ergosterol component (member of the sterol family) of the fungal membrane. For a cell to be susceptible, its membrane must contain sterols. Bacterial membranes lack sterols; therefore, this agent is ineffective against bacteria.  Mechanism of Action Amphotericin B binds to components of the fungal cell membrane-increasing permeability. This results in intracellular leakage, which reduces the organism's viability.  Depending on agent concentration and fungal susceptibility, the action could be fungistatic or fungicidal.    **Title: Mechanism of antifungal drugs** - Cell wall - Cell membrane - DNA - Proteins - Echinocandins, triterpenoids - Azoles, polyenes, allylamines - 5-fluorocytosine - Sordarins Indications and Therapeutic Uses - **Systemic Fungal Infections**: Amphotericin B is a drug of choice for most systemic mycoses.   Side Effects and Adverse Reactions **Side Effect** **Description** --------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Infusion Reactions Fever, chills, rigors, nausea, and headache frequently occur during infusion due to the release of proinflammatory cytokines. Pretreatment with diphenhydramine plus acetaminophen can reduce mild reactions. Phlebitis can also occur. Pretreatment with heparin, administration through a large central vein, and changing peripheral venous sites can minimize risk. Nephrotoxicity Amphotericin B can commonly cause this adverse effect. This risk is dose dependent. If the total dose exceeds 4g, renal impairment is likely. Hypokalemia Clients with renal impairment are at risk of this adverse effect with amphotericin use. Hematologic Effects Amphotericin B use increases the risk of bone marrow suppression, resulting in normocytic, normochromic anemia. Intrathecal Injection Reactions Intrathecal administration can cause nausea, vomiting, headache, and back, leg, and abdominal pain. Rare reactions can include visual disturbances, hearing impairment, and paresthesia. Precautions and Contraindications **Precautions** - Amphotericin B dosage should be reduced in clients with renal impairment.  - Due to toxicity, this drug should be administered for the shortest time possible. Treatment is usually 6 to 8 weeks but may last 3 to 4 months.  **Contraindications** - Contraindicated in clients with severe renal impairment.  **Black Box Warning** - Because of its toxicity, amphotericin B should only be administered for a potentially life-threatening infection.    Drug Interactions - Concomitant use of amphotericin B with other **\[nephrotoxic agents\]** such as **\[aminoglycosides, cyclosporine, or NSAIDs\]** increases the risk for renal damage.    - Amphotericin potentiates the antifungal action of **\[flucytosine\]**, requiring a reduction in amphotericin B dosage. Combining these two medications can enhance antifungal treatment and reduce the potential for toxicity.  Dosing, Administration, & Client Teaching **Dosing** - Dosing varies based on the condition, severity, and client response.  - Check drug dosing guidelines for individualized dosing.  - Amphotericin B dosing is individualized based on disease severity and client tolerability.    - Initial test dose should be administered to assess the client's reaction.  - Amphotericin B is available in four formulations- conventional and three lipid-based formulations. The lipid-based formulations are as effective as the conventional but are more costly and cause less toxicity.  - All formulations are administered intravenously and given daily or every other day for several months.  **Administration** - IV administration. **Client Teaching** - Educate clients on potential adverse effects and when to report them.  Labs to Monitor **Basic Metabolic Panel** - Monitor BUN, creatinine, and creatinine clearance during drug initiation and every 3-4 days.  - Monitor potassium and magnesium on initiation and every 3-4 days.  **Complete Blood Count (CBC)** - Monitor CBC for anemia on initiation and every 3-4 days.