Antifungal Drugs

In comparison with bacteria or viruses, fungi are more complex organisms. They have ribosomes, cellular membrane components, and a nuclear membrane. Therefore, antibacterial antibiotics are, as a rule, ineffective against pathogenic fungi.

Fungal infections (mycoses) occur less than bacterial or viral infections. However, that statement may be untrue for a few geographical regions that are favorable for the existence and growth of specific fungal pathogens. A few fungal infections can spread to the surface of the body and cause local disturbances, while others can be systemic and life threatening. Some of these organisms (for example, Candida) can spread from a superficial location to internal organs, leading to systemic diseases with serious complications. Fungal (mycotic) infections cause a lot of discomfort, and as a rule, are difficult to cure. Fungal infections are conventionally divided into three categories: dermatophylic, mucocutaneous, and systemic.

The most widespread are dermatophytic fungal infections, which include skin, hair, and nails. Most infections can be cured by using topical drugs, such as tolnaftate, undecylenic acid, haloprogin, clotrimazole, and miconazole. Griseofulvin is used orally for deep infections, in particular for infections of the nail bed. Currently, ketoconazole is widely used for treating chronic dermatophytes.

Mucocutaneous infections caused primarily by the fungus Candida albicans occur in regions of moist skin and mucous membranes (i.e. gastrointestinal tract, perianal, and vul-vovaginal areas). Amphotericin B, miconazole, clotrimazole, and nystatin are used topically to treat such infections. For chronic infections, ketoconazole is taken orally.

Systemic fungal infections are very rare, although they do present a serious problem since they are naturally chronic and difficult to diagnose and treat. So, antifungal drugs are medications used to treat fungal infections such as athlete's foot, ringworm, and candidia-sis (thrush) as well as serious systemic infections like cryptococcal meningitis. Antifungals work by exploiting differences between mammalian and fungal cells to kill the fungal organism and without significantly harming the host.

From the chemical point of view, antifungal drugs can be divided into polyenes, imida-zole and triazole derivatives, allylamines, and others. The polyenes (nystatin, amphotericin B, natamycin) 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. The imidazole and triazole groups of antifungal drugs (imidazoles: miconazole, ketoconazole, clotrimazole, econazole, mebendazole, butoconazole, fluconazole) inhibit the enzyme cytochrome P450

14a-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell-wall synthesis. These drugs also block steroid synthesis in humans. Allylamines (naftifine, terbinalfine, butenafine, amorolfine) inhibit the enzyme squalene epoxidase, another enzyme required for ergosterol synthesis.

Others: Griseofulvin binds to polymerized microtubules and inhibits fungal mitosis. Flucytosine is an antimetabolite. From the medical point of view, antifungal drugs are considered dermatophytic, mucocutaneous, and systemic.

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