HEALTH AND MEDICAL PRODUCTS:ANTIFUNGUS FOOTTREA TMENTS.

ANTIFUNGUS FOOTTREA TMENTS

Athlete’s foot is a relatively common skin infection of the feet caused by moldlike fungi called dermatophytes. Also known as tinea (the medical word for fungus) pedis (the Latin word for foot), this brief (or potentially long-term) condition is associated with symptoms such as intense itching of feet, cracked, blistered, or peeling areas of the skin (especially between the toes), and redness and scaling on the foot soles. Fungal or tinea infections may also be referred to as ringworm, perhaps because of the scaly, ring-type rash associated with fungal skin infections. The three main types of tinea pedis infections are toe web (interdigital) infection, moccasin-type infection, and vesicular infection. While tow web infection usually involves mild scaling or maceration (severe breaking down) of the skin between the fourth and fifth toes, moccasin-type infection causes scaly thickened skin on the sole and heel of the foot. Vesicular infection involves blistering on the skin of the instep, between the toes, on the sole of the foot, on the top of the foot, or on the heel, causing severe inflammation. Both toe web and vesicular infections may be associated with additional bacterial infection. In some individuals, the fungal infection may also spread to one or more toenails (called onychomycosis), causing the nail to appear unusually thickened and cloudy yellow. Onychomycosis is often associated with moccasin-type tinea pedis infection.

Susceptibility to tinea pedis is increased by poor hygiene, occlusive footwear, prolonged moist skin conditions, and minor skin and nail injuries. Such tinea infections are contagious and can be transmitted through direct contact with infected skin or contact with items such as shoes, stockings, or socks. Also, many cases of tinea pedis may be traced to the use of public recreational or sports facilities and direct skin contact (e.g., walking with bare feet) with warm and damp fungus-contaminated areas around locker room showers, spas, and swimming pools. Because the infection was common among athletes who frequently used such facilities, “athlete’s foot” became an increasingly popular term for tinea pedis. Athlete’s foot may also spread to other parts of the body of an infected person, notably to the groin (tineacruris; “jock itch”) and underarms, by contaminated bedding or clothing and by scratching the foot infection and then touching elsewhere on the body.

While the top layer of human skin normally hosts a variety of micro- organisms, including dermatophytes, advantageous environmental conditions may cause these organisms to multiply rapidly and subsequently cause various types of infections. The dermatophytes that cause tinea pedis thrive in warm, moist environments. The dermatophytes that cause athlete’s foot may live on horny nonliving tissues of the hair, nails, and outer skin layers, as the fungus lacks the ability to penetrate the viable tis- sues of an immunocompetent host. Dermatophytes include three genera (Epidermophyton, Trichophyton, and Microsporum) of fungi that commonly cause skin disease in humans and other animals. Of the three dermato- phyte genera, Epidermophyton is a filamentous multicellular fungus that includes the pathogenic species Epidermophyton floccosum, which specifically causes athlete’s foot.

Over-the-counter antifungus (fungistatic or fungicidal) medications typically include active ingredients such as allylamines (e.g., butenafine [benzylamine derivative], terbinafine), azoles (e.g., clotrimazole, miconazole), thiocarbamates (e.g., tolnaftate), hydroxypyridinones (e.g., ciclo- pirox [C12H17NO2]), or weak acids (e.g., undecylenic acid [CH2= CH(CH2)8CO2H]). These cream, lotion, powder, gel, or spray medica- tions are typically applied topically to the infection site multiple times per day for at least several weeks.

Fungi possess a cell wall in addition to a plasma membrane composed of ergosterol, a key membrane lipid. Both terbinafine and butenafine in- hibit ergosterol biosynthesis via the inhibition of squalene epoxidase, an enzyme required for fungal plasma membrane ergosterol synthesis, and subsequently prevent the fungal organism from maintaining a normal intracellular environment. While typically used in concert with a kera- tolytic agent (e.g., salicylic acid plus benzoic acid) that aids in removing the keratinous layer to allow increased penetration of the antifungus agent, tolnaftate also inhibits squalene epoxidase, resulting in the accu- mulation of intracellular squalene and decreased ergosterol biosynthesis. Tolnaftate distorts the fungal hyphae and stunts mycelial growth. Con- ceptually related to allylamines, azoles such as miconazole inhibit the cytochrome P450 microsomal enzyme system and also decrease the con- version of 14-a-methylsterols to ergosterol, thereby inhibiting ergosterol biosynthesis. Clotrimazole, although related to other azoles, acts on fungal cell membranes and interferes with amino acid transport into the organism.

Ciclopirox acts by chelation of polyvalent cations (Fe3+ or Al3+), result- ing in the inhibition of the metal-dependent enzymes that are respon- sible for the degradation of damaging peroxides within the fungal cell. A mixture of undecylenic acid and its zinc salt is also used as an active in- gredient in athlete’s foot remedies. A natural component of human sweat, undecylenic acid has both antifungus and astringent (skin-drying) properties, and the addition of zinc undecylenate liberates undecylenic acid upon contact with areas of moisture. While the fungistatic mechanism of action of this compound is not fully known, possible mechanisms include interference with fatty acid biosynthesis (which can inhibit fungal hyphae [germ tube] formation) and disruption of fungal cell cytoplasm pH by serving as a proton carrier.