Amphotericin

Emma Farrell

UNDER REVIEW (April 2017)

Mechanism of Action:

Antifungal drug (polyene). Unlike bacteria, yeasts and fungi are eukaryotes, as are humans (and all other plants and animals). The basic structure of a fungal cell is nearly identical to a human’s. This means finding a target for an antifungal to attack, that does not exist in the infected organism, is more difficult. Polyene antifungals such as amphotericin B and nystatin bind with sterols in the fungal cell wall, principally ergosterol. This causes the cell’s contents to leak out and the cell dies. Human (and other animal) cells contain cholesterol rather than ergosterol so are much less susceptible.

Lecture and CAL materials:

Drug specifics

Alternative drug name Amphoteracin B
Effects Active against most fungi and yeasts oral and oropharyngeal candidiasis (by mouth), systemic fungi and yeasts (IV).
Adverse actions See eBNF.
Dose See BNF – oral, IV (lipid preparation)
Interactions See eBNF.
Contraindications not specified
Comments An antifungal drug is medication used to treat fungal infections such as athlete's foot, ringworm and candidiasis (thrush), as well as serious systemic infections like cryptococcal meningitis. The polyene antifungals include amphotericin and nystatin; neither drug is absorbed when given by mouth. They are used for oral, oropharyngeal, and perioral infections by local application in the mouth. When given parenterally amphotericin is toxic and side-effects are common. Lipid formulations of amphotericin (Abelcet®, AmBisome®, and Amphocil®) are significantly less toxic and are recommended when the conventional formulation of amphotericin is contra-indicated because of toxicity, especially nephrotoxicity or when response to conventional amphotericin is inadequate; lipid formulations are more expensive. Nystatin is used principally for Candida albicans infections of the skin and mucous membranes, including oesophageal and intestinal candidiasis. Other antifungals include imidazoles and triazoles (see clotrimazole), caspofungin, flucytosine, griseofulvin and terbinafine. Terbinafine is the drug of choice for fungal nail infections and is also used for ringworm infections where oral treatment is considered appropriate. Griseofulvin is effective for widespread or intractable dermatophyte infections but has been superseded by newer antifungals, particularly for nail infections. It is usually well tolerated and is licensed for use in children. Duration of therapy is dependent on the site of the infection and may be required for a number of months. Caspofungin and flucytosine are given by intravenous infusion for invasive Aspergillus and Candida infection. Flucytosine is often used with amphotericin in a synergistic combination. Terbinafine is an allylamines and inhibits the enzyme squalene epoxidase, another enzyme required for ergosterol synthesis. Caspofungin inhibit the synthesis of glucan in the cell wall, probably via the enzyme 1,3-β; glucan synthase. Flucytosine is an antimetabolite. Griseofulvin binds to polymerized microtubules and inhibits fungal mitosis. Fluconazole, as with other imidazole- and triazole-class antifungals, inhibits the fungal cytochrome P450 enzyme 14α;-demethylase. Mammalian demethylase activity is much less sensitive to fluconazole than fungal demethylase. This inhibition prevents the conversion of lanosterol to ergosterol, an essential component of the fungal cytoplasmic membrane, and subsequent accumulation of 14α;-methyl sterols. Fluconazole is primarily fungistatic, but may be fungicidal against certain organisms in a dose-dependent manner.
Contributors