Antifungals for the treatment of onychomycosis

Pathogenic fungi are not present in the natural microflora of humans and animals. Fungi are eukaryotes that lack chlorophyll and are not capable of photosynthesis. Most fungi are environmental saprophytes (heterotrophs) and must feed on ready-made organic matter. The body of the fungus is represented by the mycelium - a network of thin branched tubular threads called hyphae. Fungi multiply by spores. Getting into the tissues of a susceptible host during accidental inoculation, in its favorable nutrient substrates, the fungus can cause various diseases of the skin, mucous membranes and internal organs. Fungal diseases are called mycoses (from the Greek. Mykes - fungus).

healthy and fungal nail

The causes of mycoses are parasitic microscopic fungi of the genus: Arthroderma, Aspergillus, Amanita, Microsporum, Penicillium, Candida, Saccharomyces, Trichophyton, Epidermophyton and others. Systemic mycoses of internal organs are very difficult and can affect not only the skin, muscles, bones, internal organs and nervous system. Actinomycosis is a serious disease caused by the radiant fungus actinomycetes, blastomycosis is a deep mycosis of the skin, the causative agent is a pathogenic dimorphic fungus. Other diseases also belong to deep (visceral) mycoses. Superficial mycoses affect the stratum corneum, scalp, nail plates and mucous membranes.

The most common keratomycosis, which affects only the stratum corneum; dermatomycoses affect the smooth skin, epidermis and its appendages: hair, nails.

Depending on the type of pathogenic fungus and the localization of the pathological process, there are:

  • epidermophytosis - mycoses of the skin of the inguinal folds, lower legs, interdigital folds, brushes;
  • tricomycosis (from the Greek trichos - hair) - damage to the scalp, velous hair on the body;
  • trichophytosis (trichophytia), microsporia, favus (scabies);
  • onychomycosis (from the Greek onychos - nail) - damage to the nail plates of the hands or feet with dermatophytes (rarely mold or yeast).

For diseases caused by different types of pathogenic or opportunistic fungi, antifungal drugs are used. Depending on the location of the pathogenic fungus, antifungal drugs are classified into drugs for the treatment of:

  • systemic mycoses;
  • candidiasis;
  • superficial mycoses.

The chemical classification divides antifungal drugs into:

antibiotics:

  • polyene antibiotics (amphotericin B, amphoglucamine, natamycin, nystatin);
  • antipolyene antibiotics (griseofulvin);

synthetic drugs:

  • imidazole derivatives (bifonazole, isoconazole, ketoconazole, clotrimazole, miconazole, oxyconazole, omoconazole, sertaconazole);
  • triazole derivatives (itraconazole, fluconazole, thermoconazole, thioconazole);
  • allylamine derivatives (terbinafine, naftifine);
  • morpholine derivatives (amorolfine);
  • derivatives of different chemical groups: undecylenic acid cyclopirox, flucytosine, potassium iodide, etc.

Onychomycosis

Onychomycosis is caused by an infection of the nail plate. Most of the infection occurs in public baths, saunas, swimming pools. Scales that contain spores and mycelium of fungi falling on patients with onychomycosis fall to the floor, benches, bars, walkways, carpets and bedding. In conditions of high humidity, fungi can not only last a long time (years), but also multiply, which makes them an intense source of infection. A person who walks on the floor barefoot or touches household items with such scales can become infected because they stick to his skin and are fixed. The infection develops after the fungus penetrates the nail structures. In the future, they begin to activate, multiply and form tunnels, passages. When affected, the nails thicken, crumble, turn yellow and break. Sometimes the process also affects the skin, which is accompanied by itchy, scaly rashes in the area between the coats. Such diseases are characterized by a long and persistent course.

The probability of susceptibility to infection increases with age, especially in older people over 65 years, due to the presence of such chronic diseases as autonomic pathology, diabetes mellitus, peripheral circulatory disorders, osteoarthropathy of the legs and others. nail plates.

The treatment of onychomycosis is carried out strictly according to a certain scheme for a long period of time - from 2 to 4 months. In therapy, antifungals are used, which have a fungistatic and fungicidal effect and affect different stages of life and metabolism of pathogens. There are three main mechanisms of antifungal action of antifungal drugs, which as a result show their activity:

  • disorders of the structure and function of the cell wall of fungi (imidazoles, triazoles);
  • disruption of eukaryotic cell mitosis by inhibiting nucleic acid synthesis (griseofulvin);
  • inhibition of transmembrane metabolic processes across the cell membrane of fungi (cyclopirox).

Drugs of choice

GriseofulvinSection (Griseofulvinum). 125 mg is an antibiotic produced by the mold Penicillium nigricans (griseofulvum), isolated in 1939 and is a spiro derivative of benzofuran in structure. The drug has fungistatic properties against all types of fungi - trichophytes and epidermophytes. The mechanism of fungistatic action is based on the ability of the drug to inhibit the cell division of filamentous fungi in metaphase, causing characteristic morphological changes (torsion, increased branching and distortion of hyphae), disrupting the structure of the mitotic spindle and cell wall synthesis. To a small extent, the drug inhibits the synthesis and polymerization of nucleic acids. The drug has no antibacterial activity.

To create a sufficient concentration of the drug in the skin requires long-term treatment - 2-3 months min. Only on new, overgrown nails will be noticeable the first symptoms of the effectiveness of treatment.

Important! Side effects of the drug include: dyspepsia, dizziness, sometimes insomnia, allergic reactions, leukopenia. Griseofulvin is contraindicated in the suppression of hematopoiesis, liver and kidney failure, as well as in infants and pregnant women. You should not prescribe the drug to transport drivers, persons engaged in work at height or requiring increased attention, rapid mental and motor reactions. Patients should be warned of the development of possible cross-sensitivity to penicillin and of the increased effect of alcohol.

Ketoconazole(Ketoconazole) - an active broad-spectrum drug of the imidazole group with fungicidal and fungistatic activity; effective when taken orally with systemic and superficial mycoses, dermatomycosis and candidiasis. It is prescribed by a doctor for the treatment and prevention of fungal infections of the skin, hair, nails, genitals caused by pathogens sensitive to the drug.

When administered orally, the drug is well absorbed, dissolved and absorbed in an acidic environment.

Important! The drug is well tolerated by patients, but can cause dyspeptic symptoms (nausea, vomiting, diarrhea), very rarely there are allergic reactions in the form of urticaria and skin rash, headache, dizziness, gynecomastia, impotence. When the drug is used concomitantly with other drugs (fentanyl, tamsulosin, carbamazepine, salmeterol, etc. ), the concentration of the latter may increase with increasing side effects.

Contraindicated in severe hepatic, renal, pregnancy, lactation and hypersensitivity to the drug.

Ketoconazole is available in the table. 200 mg suppository. 400 mg; 2% ointment, 15 mg; cream 20 mg / g - 15 g. Used in the form of shampoos. The duration of treatment is determined individually.

Itraconazole(Itraconazole) caps. 100 mg; solution 10 mg / ml - vial150 ml - the drug has a broad spectrum of action, selectively and specifically inhibits the enzyme that catalyzes the synthesis of fungal sterols. Scope: various infections caused by dermatophytes and / or yeast and mold fungi, such as candidiasis of the mucous membranes (including the vagina), skin mycoses, onychomycosis, epidermomycosis, fungal eye lesions (keratitis), peritoneum and other localizations. Taking Itraconazole capsules immediately after a meal increases its bioavailability; the maximum concentration in blood plasma is reached within 3-4 hours. after ingestion. The drug is well distributed in tissues that are susceptible to fungal infections.

Important! When using the drug may experience side effects from the digestive system: dyspepsia (nausea, vomiting, diarrhea, constipation, loss of appetite), abdominal pain, impaired taste; headache, dizziness, allergic reactions, alopecia, hematopoietic organs (rare) - leukopenia, thrombocytopenia. Use is contraindicated in case of hypersensitivity to itraconazole and any of the components of the drug, children under 3 years of age, pregnancy and lactation.

For optimal absorption of the drug it is necessary to take the capsules without chewing, immediately after a meal, swallow whole. One course of pulse therapy for onychomycosis consists of a daily intake of 2 capsules. the drug twice a day for a week. For the treatment of fungal infections of the nail plates of the hands, two courses are recommended. For the treatment of fungal infections of the nail plates of the feet, three courses are recommended. The interval between courses, during which you do not need to take the drug, is 3 weeks.

Terbinafine(Terbinafine) - produced in the form: tab. 250 mg; 1% ointment 15, 0 g; 1% cream - 10, 15, 30 g tube; 1% spray, 20 ml. The drug is called allylamine and is prescribed for systemic and external use. The mechanism of action of Terbinafine is associated with inhibition of the initial stage of ergosterol biosynthesis (the main cellular sterol of the fungal membrane) by inhibition of the specific enzyme squalene-2, 3-epoxidase on the fungal membrane. The drug is effective against many fungi pathogenic to humans. In topical treatment, Terbinafine is more effective than azole drugs, imidazole derivatives, but comparable to itraconazole, and when administered orally, it is more effective than griseofulvin and itraconazole. Terbinafine is characterized by lipoidophilicity, rapidly diffuses into the stratum corneum of the epidermis, dermis, subcutaneous tissue, accumulates in the sebaceous glands, hair follicles and nail plates in concentrations that provide a fungicidal effect. 1 section. once daily terbinafine results in a higher cure rate and better results for each efficacy criterion (including mycological cure) than intermittent intraconazole therapy.

Naftifine(Naftifine) cream 1% - 15, 30 g; A 1% solution of 10, 20, 30 ml is a derivative of allylamines. The mechanism of action is associated with inhibition of the activity of the enzyme squalene-2, 3-epoxidase, inhibition of ergosterol biosynthesis, which leads to disruption of cell wall synthesis. Naftifine has a broad spectrum of action, acting fungicidal against dermatophytes (such as Trichophyton, Epidermophyton, Microsporum), mold (Aspergillus spp. ), Yeast-like fungi (Candida spp. , Pityrosporum) and other fungi, for example (Sphenor scorotrichosis). . . The drug has anti-inflammatory effect, reduces itching. When applied externally, it penetrates well into the skin, creating stable antifungal concentrations in its various layers.

The duration of treatment with Naftifin varies from 2 weeks to 6 months. When using the drug may appear dryness and redness of the skin, burning sensation, all these side effects are reversible and do not require cancellation.

Amorolfine(Amorolfine) nail polish 5% - 2, 5 and 5 ml, - preparation for external use, has a broad spectrum of action, providing fungistatic and fungicidal action due to damage to the cytoplasmic membrane of the fungus by disrupting the biosynthesis of sterol due to inhibition ofthe enzymes 14– gamma demethylase and 7 gamma isomerase. The drug is active against both the most common and rare pathogens of fungal infections of the nails of dermatophytes: Trichophyton spp. , Microsporum spp. , Epidermophyton spp. molds: Alternaria spp. , Scopulariopsis spp. , Hendersonula sppi. fungi of the family Dematiaceae: Cladopsorium spp. , Fonsecaea spp. , Wangiella spp. dimorphic fungi Coccidioides spp. , Histoplasma spp. , Sporothrix spp.

When applied to the nails, the drug penetrates the nail plate and further into the nail bed, almost completely during the first 24 hours. The effective concentration remains in the affected nail plate for 7-10 days. after the first application. Systemic absorption is negligible. It is applied externally. The drug is applied to damaged toes or toenails 1-2 times a week. The duration of treatment is determined individually and depends on the indications for use. Side effects are rare and manifest themselves in the form of itching, burning at the site of application. Not prescribed for young children and infants.

Undecylenic acidand its salts - antifungal drugs for external use, which have a fungistatic and fungicidal effect against dermatophytes when combined with zinc or copper salts - zinc undecylenate or copper undecylenate - the activity increases. Zinc, which is part of the drug, has an astringent effect, reduces the signs of skin irritation and promotes faster healing.

  • Undecylenic acid + zinc undecylenate (TN, ointment 30 g tube, ointment 25 g in bottles);
  • Undecylenic acid + copper undecylenate + HCV glycerol - used to treat and prevent fungal skin diseases caused by fungi (dermatophytes) sensitive to the drug.

The preparations are applied on a clean, dry surface of the affected skin 2 times a day (morning and evening). The duration of treatment is 4-6 weeks and depends on the nature, effectiveness and course of the disease. After the disappearance of the clinical signs of the disease, they continue to be used once a day. For preventive purposes - 2 times a week.

Important! Contraindication to the use of the drug is hypersensitivity to undecylenic acid and its derivatives.

Cyclopirox(Ciclopirox) nail polish 8%, floor 3 g, is a broad-spectrum antifungal drug that inhibits the capture of precursors for the synthesis of macromolecules in the cell membrane. It is used externally for the treatment and prevention of fungal infections of the skin, mucous membranes, nails, fungal vaginitis and vulvovaginitis.

The drug is applied 1-2 times a day on the affected nail, the duration of use depends on the severity of the lesion, but should not exceed 6 months.

Treatment of onychomycosis should be performed under the strict supervision of a dermatologist. As a rule, rational etiotropic complex therapy is used. Reduction or disappearance of clinical symptoms is usually observed a few days after taking the antifungal. However, to avoid recurrence of the disease, the course of treatment should be carried out completely. Against the background of clinical cure, antirelapse therapy is often given to prevent re-infection.