Amphotericin B: Mechanism of Action Quiz

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A. Amphotericin B is a naturally occurring polyene macrolide antibiotic produced by Streptomyces nodosus. In spite of its toxic potential, amphotericin B is the drug of choice for the treatment of life-threatening systemic mycoses. Mechanism of action: Several amphotericin B molecules bind to ergosterol in the plasma membranes of sensitive fungal cells. (The pores disrupt membrane function, allowing electrolytes (particularly potassium) and small molecules to leak from the cell, resulting in cell death. Antifungal spectrum: Amphotericin B is either fungicidal or fungistatic, depending on the organism and the concentration of the drug. It is effective against a wide range of fungi, including Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Blastomyces dermatitidis, and many strains of Aspergillus. [Note:Amphotericin B is also used in the treatment of the protozoal infection leishmaniasis.] Amphotericin B is administered by slow, intravenous (IV) infusion. Adverse effects: a. Renal impairment b. Hypotension c. Anemia d. Neurologic effects ______

Amphotericin B is also used in the treatment of the protozoal infection leishmaniasis.

Amphotericin B is administered by slow, intravenous (IV) infusion. Adverse effects: a. Renal impairment b. Hypotension c. Anemia d. Neurologic effects ______

Amphotericin B

5-FC is converted to 5-fluorodeoxyuridine. This false nucleotide inhibits thymidylate, an essential DNA component. Antifungal spectrum: 5-FC is ______

fungistatic

Antifungal spectrum: Amphotericin B is either fungicidal or ______

fungistatic Signup and view all the answers

Amphotericin B is either ______ or fungistatic, depending on the organism and the concentration of the drug

fungicidal Signup and view all the answers

Amphotericin B is effective against a wide range of fungi, including Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Blastomyces dermatitidis, and many strains of Aspergillus. [Note:Amphotericin B is also used in the treatment of the protozoal infection ______

leishmaniasis Signup and view all the answers

Mechanism of action

Azoles are predominantly fungistatic. Block the synthesis of ergosterol, the primary cell sterol of fungi thereby altering the cell membrane permeability of yeasts and fungi. The drug also inhibits human gonadal and adrenal steroid synthesis, leading to decreased testosterone and cortisol production. Signup and view all the answers

Antifungal spectrum

Oral ketoconazole is active against many fungi, including Histoplasma, Blastomyces, Candida, and Coccidioides, but not aspergillus species. Itraconazole has largely replaced ketoconazole in the treatment of most mycoses because of its broader spectrum, greater potency, and fewer adverse effects. Topical ketoconazole is used to treat tinea corporis, tinea cruris, and tinea pedis. Also, topical ketoconazole is used to treat tinea versicolor, cutaneous candidiasis caused by Candida species. It is also used topically in the treatment of seborrheic dermatitis and dandruff. Signup and view all the answers

Administration

When ketoconazole is administered orally, it requires gastric acid for dissolution and is absorbed through the intestinal mucosa. Administering acidifying agents before taking the drug can improve absorption in patients with achlorhydria. Signup and view all the answers

Adverse effects

In addition to allergies, dose-dependent gastrointestinal disturbances, including nausea, anorexia, and vomiting, are the most common adverse effects of ketoconazole treatment. Endocrine effects, such as gynecomastia, decreased libido, and menstrual irregularities, result from the blocking of androgen and adrenal steroid synthesis by ketoconazole. Hepatic damage Signup and view all the answers

Drug interactions and contraindications

By inhibiting CYP450, ketoconazole can potentiate the toxicities of drugs such as cyclosporine. Rifampin, an inducer of the CYP450 system, can shorten the duration of action of ketoconazole. Drugs that decrease gastric acidity, such as H2-receptor blockers, antacids, and proton-pump inhibitors, can decrease absorption of ketoconazole. Finally, ketoconazole is not be given during pregnancy. Signup and view all the answers

Clinical significance

It is clinically important because of its lack of the endocrine side effects of ketoconazole and its excellent penetrability into the CSF of both normal and inflamed meninges. Fluconazole is employed prophylactically, with some success, for reducing fungal infections in recipients of bone marrow transplants. It inhibits the synthesis of fungal membrane ergosterol in the same manner as ketoconazole. Signup and view all the answers