4. Antifungal drugs. Classification. Mechanism of action. Indications for use. Side effects. Contraindications Comparative evaluation of drugs.

Antifungal agents (antimycotics) - medicines used for the prevention and treatment of fungal infections (mycoses).

Mycoses are diseases caused by pathogenic or opportunistic fungi. Fungal infections can be systemic (deep) and superficial.

Antifungal agents differ from each other in origin (natural or synthetic), spectrum and mechanism of action, effect (fungicidal or fungistatic), indications for use (local or systemic infections), methods of administration (oral, parenteral, external).

Classification:

I. Means used in the treatment of diseases caused by pathogenic fungi:

1. With systemic or deep mycoses (coccidioidomycosis, paracoccidioidomycosis, histoplasmosis, cryptococcosis, blastomycosis):

- antibiotics (amphotericin B, mycoheptin);

- derivatives of imidazole (miconazole, ketoconazole);

- derivatives of triazole (itraconazole, fluconazole).

2. With superficial (dermatomycosis):

- antibiotics (griseofulvin);

- derivatives of N-methylnaphthalene (terbinafine);

- derivatives of nitrophenol (chloronitrophenol);

- iodine preparations (alcohol solution of iodine, potassium iodide).

II. Drugs used in the treatment of diseases caused by opportunistic fungi (for example, with candidiasis):

- antibiotics (nystatin, levorin, amphotericin B);

- derivatives of imidazole (miconazole, clotrimazole);

- bis-quaternary ammonium salts (dequalinium chloride).

Polyene antibiotics- antimycotics of natural origin produced by molds: Streptomyces nodosum (amphotericin B), Actinomyces levoris Krass (levorin), actinomycetes Streptoverticillium mycoheptinicum (mycoheptin), actinomycetes Streptomyces noursei (nystomyces noursei). These are substances with a complex chemical structure containing a polyunsaturated macrocyclic lactone ring.

Mechanism of action.

The drugs firmly bind to ergosterol (the main component of the fungal membrane), as a result of which hydrophilic pores are formed in the membrane, through which ions and low molecular weight substances escape from the cell, which leads to cell death

Spectrum of action. Polyenes differ in their spectrum of action. Topical preparations (nystatin, natamycin, levorin) act mainly on fungi of the genus Candida spp. Preparations for systemic use have a wide spectrum of action. Also, some drugs are characterized by activity against some protozoa - Trichomonas (natamycin), leishmania and amoebas (amphotericin B). Insensitive to amphotericin B causative agents of zygomycosis. Dermatomycetes (genus Trichophyton, Microsporum and Epidermophyton), Pseudoallescheria boydi, etc. are resistant to polyenes.

Common systemic side effects of polyenes taken by mouth are: nausea, vomiting, diarrhea, abdominal pain, and allergic reactions; with local use - irritation and burning sensation of the skin. Amphotericin B - chills, nausea, vomiting, headache, hypotension, phlebitis, as well as nephro-, hepato-, neurotoxicity, hematological reactions, electrolyte metabolism disorders.

Contraindications: diseases of the gastrointestinal tract (gastric ulcer and duodenal ulcer, acute gastroenterocolitis), impaired renal and liver function, individual drug intolerance.

Azoles - the most numerous group of synthetic antifungal agents.

Mechanism of action.

The antifungal effect of azoles, like polyene antibiotics, is due to a violation of the integrity of the fungal cell membrane, but the mechanism of action is different: azoles disrupt the synthesis of ergosterol - the main structural component of the fungal cell membrane

Indications for use Candidiasis of the skin, mucous membranes of the mouth, pharynx, esophagus and intestines - Systemic candidiasis. - Keratomycosis (pityriasis versicolor, trichosporosis). -Dermatophytosis - Subcutaneous mycoses (sporotrichosis, chromomycosis). - Pseudo-allesheriosis. - Onychomycosis. - Deep endemic mycoses. - Cryptococcosis (skin, lungs and other organs), cryptococcal meningitis. - Prevention of fungal infections in patients with reduced immunity, transplanted organs and malignant neoplasms.

Side effects -disorders of the gastrointestinal tract, including abdominal pain, impaired appetite, nausea, vomiting, diarrhea or constipation, increased activity of hepatic transaminases, cholestatic jaundice; - on the part of the nervous system and sensory organs, including headache, dizziness, drowsiness, paresthesia, tremors, convulsions, visual impairment; - hematological reactions - thrombocytopenia, agranulocytosis; - allergic reactions - skin rash, itching,

Allylamines- synthetic drugs that have a predominantly fungicidal effect. Unlike azoles, they block the earlier stages of ergosterol synthesis

Indications for use 1. Mycosis of the external auditory canal. 2. Fungal lesions of the skin and skin folds, epidermophytosis, trichophytosis, interdigital mycoses. 3. Onychomycosis. 4. Pityriasis versicolor. 5. Mycoses, in the area of ​​hair growth and / or with hyperkeratosis. 6. Skin lesions with Candida fungus (naftifine). 7.Mixed mycoses, accompanied by bacterial infections (naftifine).

Side effects When administered orally - loss of appetite, nausea, abdominal pain, diarrhea, skin reactions in the form of a rash. When applying the cream - hyperemia, itching, burning sensation, allergic reactions.

Contraindications 1. Allergy to the active substance or auxiliary elements. 2. Naftifine solution should not be applied to open wounds. 3. Pregnant and lactating women with caution.