ANTIFUNGAL AGENTS

2010

ANTIFUNGAL AGENTS are antimicrobial drugs used to treat infections caused by fungal microorganisms. They may be antibiotics produced naturally, or purely synthetic. Fungal infections are not usually a major problem in healthy, well-nourished individuals. But, superficial, localized infections, such as thrush (caused by Candida albicans), and athlete’s foot and ringworm (caused by Tinea fungi of the dermatomycoses group), are common. These can readily be treated with topical application of antifungals. Severe infections occur most frequently where the host’s immunity is low, e.g. following immunosuppression for transplant surgery or in AIDS. Unfortunately, the most potent antifungal drugs taken systemically tend to be toxic.

Amphotericin is a complex amphoteric polyene ANTIBIOTIC that binds to cell membranes and forms a pore through which ions can pass, with consequences that include loss of potassium ions from within the cell. Since the antibiotic binds more readily to fungal cell membranes than mammalian, its action is relatively selective. It can potentiate the action of certain other antifungals, and it may be used with flucytosine. Also, it confers antifungal activity on rifampicin (normally antibacterial). As it has an appreciable renal toxicity, it needs to be used with caution in some patients. Nystatin is a polyene antibiotic similar in structure to amphotericin, often used for local treatment.

Griseofulvin is a narrow-spectrum antifungal antibiotic with fungistatic properties, which is mainly used for large-scale ringworm (dermatophytic) infections of the skin, nails, scalp and hair.

Imidazole (azole) antimicrobials are a large group of synthetic broad-spectrum drugs, many with antifungal activity, such as clotrimazole, econazole. isoconazole, ketoconazole and miconazole. They work by blocking the synthesis of ergosterol, a major constituent of the fungal membrane, and are active against most fungi and yeasts. They can be used to treat infections of the skin and mucous membranes, the hair and nails, including candidiasis and thrush. Some may be used systemically, though there may be hepatotoxicity (e.g. miconazole, isoconazole and ketoconazole).

Terbinafine is an allylamine active against a wide range of fungal pathogens. It interferes with an enzyme, squalene epoxidase, involved in fungal cell wall synthesis. It is painted onto the skin and taken up rapidly. Flucytosine is a synthetic agent used for systemic fungal infections of the yeast type.