Antimycotic - what is it ... Characteristics, classification and active ingredients

In recent decades, mycoses in medicine have become a serious problem. Their number is constantly increasing, which is associated with the spread of immunodeficiency states, the use of cytostatic drugs, the introduction of new invasive procedures, and other factors. Superficial mycoses acquire the character of chronic, and generalized have a high mortality rate. Antimycotics are used to treat this type of disease.

Antimycotic: what is it?

Antimycotics are called antifungal agents, which are characterized by specific activity against fungi and mushroom-like organisms of microscopic sizes (micromycetes) that cause diseases in humans. They also say about such drugs that they have a fungicidal effect.

This group of drugs includes several varieties of chemical compounds. They are divided into groups depending on the composition and structure, the spectrum of therapeutic activity, the mechanism of absorption in the human body and metabolism, dosage form.

Appearance story

Even at the beginning of the 20th century, medicine practically did not know what antimycotics are. Fungal diseases were treated with potassium iodide and local antiseptics. Despite the fact that these pathologies have been known since antiquity, the most common pathogens were discovered only in the middle of the XIX century, and the development of pharmaceutical production was very late compared to antibiotics.

Most fungi are resistant to antibacterial agents. Only a few of the antibiotics are active against these microorganisms. One of the first such drugs was Nystatin. It began to be used in therapeutic practice since 1954 for the treatment of infections caused by yeast-like fungi of the genus Candida.

The first specific antimycotic agent was Griseofulvin. Since 1958, it has been used for fungal skin diseases. Initially, in medicine, an approach to the treatment of mycoses with local agents was practiced. The appearance of this medicine has changed the emphasis in therapy - it has shifted towards systemic drugs.

To treat deep mycoses affecting the internal organs, Amphotericin B was synthesized in 1956, followed by imidazole derivatives (the second generation of antimycotics), triazoles and Terbinafine (the third generation). They revolutionized the treatment of mycotic diseases. Currently, in medicine, there are about 10 systemic and several dozen local antifungal agents.

Operating principle

Studying the mechanism of action on fungi helps to better understand what antimycotics are, and also to find out the causes and types of pathogens resistance to these drugs, to determine their toxicity to the human body. According to the general effect exerted on fungal cells, 2 large groups of drugs are distinguished:

• fungicidal, leading to the complete death of the microorganism due to a violation of the basic vital functions (most often by destruction of the membrane);
• fungistatic, slowing the appearance and growth of new cells, stopping the processes necessary for building their biomaterial during reproduction.

A quantitative characteristic of antifungal activity is the minimum concentration of a substance that exerts one of the two types of exposure described above. Cell death with the use of the second group of antimycotic drugs also occurs, but this is observed when a certain concentration level or time period is exceeded.

Unlike animals, fungi have a cell wall formed mainly from chitin (in plants, from cellulose). It also includes ergostein, a steroid compound (cholesterol in animals) and glucans, polysaccharides from glucose monomers. These components are the main targets for antifungal drugs.

Their mechanism of action in modern medicine is still not well understood, and the number of targets and promising active substances is constantly replenished. New antimycotics appear that suppress the movement of electrons, affect the structure of DNA, and also have other properties.

Many of the drugs used not only have effects inherent in their classification group, but also additional ways of influencing fungal cells. The fungicidal effect can be supplemented by fungistatic, which consists in the fact that after some time in the microorganisms there is a shortage of substances necessary to perform vital functions, or toxins accumulate.

Classification by method of exposure

Classification of antimycotics according to the mechanism of action is carried out according to the following scheme:

Means acting on the outer wall of cells and the cytoplasmic membrane:

a) inhibiting the formation of ergosterol, which leads to a violation of membrane permeability and metabolic processes (imidazole and triazole derivatives, allylamines, salts of thiocarbamic acids and morpholines);

b) directly interacting with ergosterol (polyene antibiotics-macrolides) - Levorin, Amphotericin B, Nystatin;

c) agents that interfere with the production of membrane sphingolipids involved in the transmission of signals between cells and their recognition in immune mechanisms (antibacterial drugs "Aureobazidin A", acremolides);

d) drugs that worsen the synthesis of chitin (antibiotics polyoxins and niccomycins) and glucan (echinocandins, papulacandins); the latter type of drugs has a narrow spectrum of action, since glucan forms the cell walls mainly in yeast fungi.

Means that affect the processes that occur inside the cell (reproduction, protein synthesis and metabolism). They are divided into the following groups according to the type of cellular components, the synthesis of which they suppress:

a) nucleic acids - these drugs include the synthetic analogue of pyrimidine - "Flucytosine"; when it enters the fungal cell, it transforms into 5-fluoracil, which inhibits the synthesis of RNA and DNA, and this prevents the growth of microorganisms, that is, this substance has a predominantly fungistatic effect;

b) proteins - this group of drugs includes sordarin, Cispentacin, Azoxibacillin; microtubules in the division spindle system (they ensure the distribution of chromosomes between dividing cells); a typical representative of such antifungal antibiotics is Griseofulvin, which has both fungicidal and fungistatic effects.

Antimycotic resistance

According to international medical research, resistance to antibacterial and antifungal agents is now becoming a global threatening problem. In modern mycology and medicine, two trends are revealed - an increase in the number of chronic recurrent diseases and an increase in the risk of developing resistance of fungi while taking new-generation drugs.

So why does pathogen resistance increase and what is it? Antimycotics with a wide spectrum of activity and low toxicity have reduced mortality from systemic fungal infections, but their specific nature of the effect (inhibition of the enzyme systems of the fungal cells) leads to an increase in mutations of microorganisms and the natural selection of the most resistant ones. Therefore, special attention in medicine is given to monitoring the resistance of fungal strains.

The methodology for determining sensitivity to antimycotics is still not well developed. This is due to the low degree of reproducibility of the results in different laboratories. The difficulty is that fungi, unlike bacteria, are eukaryotes. A quantitative indicator of their resistance is the assessment of the minimum inhibitory concentration for a given antifungal drug. In resistant strains, it is significantly higher.

Types of resistance and causes

There are 2 types of fungal resistance:

1. True, which manifests itself from the beginning of taking the medicine. The reason for this stability is the lack of influence of the active substance on the target or the impossibility of its achievement as a result of a long chain of metabolic transformations, as well as the presence of specific differences in the synthesis of vital substances in different species of fungi.
2. Acquired, developing during the treatment of those strains that were initially sensitive to this antimycotic. Resistance arises as a result of adaptive reactions from microorganisms. This type of resistance is recorded in all types of antifungal drugs. Most often, this phenomenon occurs during treatment with "Flucytosine" and azoles.

The causes and provoking factors of acquired resistance also include:

• the presence of energy-dependent systems that control the entry of antimycotics into the cell;
• adaptation processes characterized by an increase in the number of target enzymes;
• the development of fungal cells in metabolic pathways;
• long-term low-dose antifungal therapy for prevention;
• immunodeficiency states.

Classification

In addition to the classification by the mechanism of action, antimycotic drugs are distinguished by the following signs:

1. By origin: natural, synthetic.
2. According to indications for use: local, systemic.
3. By the method of administration: orally, parenterally (intramuscularly or intravenously), externally.
4. By chemical structure: polyenes (Amphotericin B and its lipid complex, Nystatin), azoles (Fluconazole, Voriconazole, Itraconazole, Ketoconazole), glucan synthesis inhibitors - echinocandins (Caspofungin), fluoropyridimines ("Flucytosine"), derivatives of morpholine ("Amorolfin"), allylamines ("Terbinafine", "Naphthyphine"), grisans ("Griseofulvin").

Currently, there are more than 100 items and 20 dosage forms of drugs on the pharmaceutical market. Of these, the most widely used group of azole antimycotics. Representatives of this group are characterized by a fungistatic effect.

For the treatment of superficial forms of mycoses, Nystatin is most often used. Of the promising antifungal agents awaiting widespread adoption, the following can be distinguished: Voriconazole, Posaconazole, Ravukonazole, Ambizom, Niotran.

Systemic drugs

Of the systemic antifungal agents, the following are most prevalent:

• grisans - "Griseofulvin";
• polyenes - "Amphotericin B" and its lipid complex;
• azoles - "Voriconazole", "Itraconazole", "Ketoconazole", "Posaconazole", "Fluconazole";
• allylamines - "Terbinafine".

Indications for the appointment of such drugs are the following conditions:

• candidiasis of the genitals, urinary tract, mucous membranes of the mouth, esophagus, intestines;
• diaper rash of skin folds;
• pityriasis versicolor;
• suppurative processes;
• generalized fungal lesions involving the heart muscle, inner lining of the heart, bronchi and lungs, abdominal cavity;
• bacterial complications, etc.

Systemic antimycotics in dermatology have priority over local drugs. This is due to the fact that they guarantee deep penetration and accumulation of the active substance in the structure of the skin, nails and hair, as well as slow excretion after the end of administration. According to medical statistics, the effectiveness of such therapy is 3 times higher than the local treatment. In the case of simultaneous damage to the gastrointestinal tract, peripheral vessels, with keratinization of the nail bed, combination therapy is prescribed.

Topical preparations

The most popular external antifungal antimycotics in Russia are drugs based on terbinafine, ketoconazole and clotrimazole. They are available in a variety of dosage forms:

• ointment;
• cream;
• solution;
• gel;
• aerosol.

The table below provides a list of antimycotic drugs and describes their characteristics for the external treatment of dermatitis.

Nail treatment

In the local therapy of onychomycosis - a fungal infection of the nails - the following antimycotics are used ointments, creams and varnishes (the active substance is indicated in brackets):

• Mikospor (bifonazole);
• Nizoral (ketoconazole);
• Canesten (clotrimazole);
• "Pevaril" (econazole nitrate)
• "Travogen", "Travocort" (isoconazole);
• "Mykozolon", "Mykozon" (miconazole);
• "Batrafen" (cyclopiroxolamine);
• Loceryl (amorolfine);
• Lamisil, Exifin (terbinafine);
• Exoderil (naphthyne) and other drugs.

With superficial damage to the nail plate, local preparations can be quite effective. Systemic antimycotics for the treatment of nail fungus are indicated in the following cases:

• total damage (more than 3 fingers are involved, more than a third of the nail plate is damaged);
• a combination of mycosis of the feet and hands with fungal infection of the nails;
• localization of the fungus on the nails of the feet;
• patient's age is more than 25 years.

We hope you find this information useful.