Antibiotics of the sulfonamide group. Sulfanilamide preparations - a list. Mechanism of action of sulfonamides, use and contraindications. Undesirable effects of sulfonamides in children.

Sulfanilamide preparations (synonymous with sulfonamides) - synthetic broad-spectrum chemotherapeutic agents from the group of derivatives of sulfanilic acid amide (sulfanilamide).

Streptococci, staphylococci, diplococci (gonococci, meningococci, pneumococci), intestinal, dysentery, diphtheria and anthrax bacilli, brucella, vibrio cholerae, actinomycetes, chlamydia (causative agents of trachoma, ornithosis, etc.), as well as causative agents of anaerobic infection ( clostridia), some protozoal infections (malaria, toxoplasmosis). In addition, to sulfa drugs individual pathogens of deep mycoses (nocardin, actinomycetes) are sensitive. Some sulfa drugs(sulfadimethoxine, sulfapyridazine, sulfalene) are active against mycobacteria leprosy (see. Anti-leprosy drugs). Among those resistant to sulfa drugs include salmonella, Pseudomonas aeruginosa, mycobacterium tuberculosis, spirochetes, leptospira and viruses. For sensitive microorganisms sulfa drugs in concentrations in which they accumulate in the body in therapeutic doses, they act bacteriostatically.

Mechanism of antimicrobial action sulfa drugs due to the fact that they block the process of synthesis of dihydrofolic acid at the stage of formation of dihydropteroic acid from dihydropteridine and para-aminobenzoic acid (PABA) with the participation of the enzyme dihydropteroate synthetase (dihydrofolate synthetase). It is believed that the violation of the synthesis of dihydropteroic acid occurs primarily as a result of the inclusion sulfa drugs instead of PABA as a substrate for dihydropteroate synthetase, tk. by chemical structure sulfa drugs are similar to PABA. As a result, the formation of analogues of dihydrofolic acid, which do not have its inherent biological activity, occurs. In addition, when interacting sulfa drugs with dihydropteridine in the presence of ATP and magnesium ions, an intermediate metabolite is formed that inhibits dihydropteroate synthetase, which leads to inhibition of the formation of dihydrofolic acid. It is also possible that sulfa drugs prevent the inclusion of dihydropteridine in the synthesis of dihydrofolic acid. Ultimately, a violation of the formation of dihydrofolic acid under the influence sulfa drugs leads to a decrease in the formation of tetrahydrofolic acid and the resulting inhibition of nucleotide biosynthesis and a delay in the development and reproduction of microorganisms. These features of the mechanism of action explain the fact that sulfa drugs only those microorganisms in which the process of synthesis of dihydrofolic acid occurs are sensitive. Microorganisms and macroorganism cells utilizing ready-made dihydrofolic acid from the external environment, to action sulfa drugs not sensitive.

With an excess of PABA and its derivatives in the medium, for example, novocaine, anesthesin, etc., as well as methionine, folic acid, purine and pyrimidine bases, antimicrobial activity sulfa drugs decreases. Decrease in activity sulfa drugs in the presence of pus and wound discharge is associated with a high content of PABA and other antagonists of sulfanilamide drugs in these substrates.

Antimicrobial effect sulfa drugs enhance drugs (for example, trimethoprim), which inhibit the conversion of dihydrofolic acid to folic (tetrahydrofolic) acid by inhibiting the enzyme dihydrofolate reductase. With the simultaneous use sulfa drugs with trimethoprim, the synthesis of tetrahydrofolic acid is disrupted in two successive stages - at the stage of formation of dihydrofolic acid (under the influence of sulfa drugs) and at the stage of transformation of the latter into tetrahydrofolic (under the influence of trimethoprim), resulting in a bactericidal effect.

After being absorbed into the blood sulfa drugs reversibly, but to an unequal degree, binds to plasma proteins. In a bound form, they do not have an antimicrobial effect and show it only as the drugs are released from this connection. On the selection speed sulfa drugs from the body, the degree of their binding to plasma proteins does not affect. Metabolized sulfa drugs in the liver mainly by acetylation. The resulting acetylated metabolites sulfa drugs do not possess antimicrobial activity and are excreted from the body through the kidneys. In the urine, these metabolites can precipitate in the form of crystals, causing the appearance of crystalluria. The severity of crystalluria is determined not only by the degree of transformation of individual sulfa drugs in acetylated metabolites and the size of the doses of drugs, but also the reaction of urine, tk. these metabolites are poorly soluble in an acidic environment.

In accordance with the characteristics of pharmacokinetics and application among sulfa drugs distinguish between the respective subgroups. For example, select a subgroup sulfa drugs well absorbed from the gastrointestinal tract. Such sulfa drugs used for systemic treatment of infections and for this purpose are administered orally and parenterally. Depending on the speed of their selection among sulfa drugs This subgroup is distinguished: short-acting drugs (half-life less than 10 h) - streptocide, sulfacyl sodium, etazol, sulfadimezin, urosulfan, etc .; intermediate-acting drugs (half-life 10-24 h) - sulfazine, sulfamethoxazole, etc.; long-acting drugs (half-life from 24 to 48 h) - ulfapiridazine, sulfadimethoxine, sulfayunomethoxine, etc.; long-acting drugs (half-life more than 48 h) - sulfalene.

Long-acting sulfonamides differ from sulfa drugs short-acting, higher lipophilicity and therefore they are reabsorbed in significant amounts (up to 50-90%) in the renal tubules, and are more slowly excreted from the body.

To a subgroup of poorly absorbed from the gastrointestinal tract sulfa drugs include sulgin, ftalazol, and ftazin. These drugs are used to treat intestinal infections (colitis and enterocolitis of bacterial etiology, including bacillary dysentery).

Subgroup sulfa drugs intended for topical use usually include soluble sodium salts of drugs that are well absorbed from the gastrointestinal tract, for example, etazol sodium, sulfapyridazine sodium, soluble streptocide, etc., as well as silver sulfadiazine. Preparations of this subgroup in the appropriate dosage forms (solutions, ointments, etc.) are used topically for the treatment of purulent infections of the skin and mucous membranes, infected wounds, burns, etc.

In addition, among sulfa drugs emit the so-called salazosulfanamides - azo compounds synthesized on the basis of some sulfa drugs systemic action and salicylic acid. These include salazopyridazine, salazodimethoxine, and salazosulfapyridine, which are used primarily for the treatment of ulcerative colitis. The effectiveness of salazosulfanamides in this disease is associated with the presence of not only antimicrobial activity, but also pronounced anti-inflammatory properties, which are due to the formation of aminosalicylic acid in the intestine during the biotransformation of drugs of this group, which has an anti-inflammatory effect.

In modern clinical practice Combination preparations containing sulfonamides and trimethoprim are also widely used. Such combined preparations include biseptol containing sulfamstoxazole and trimethoprim (5:1 ratio) and sulfatone containing sulfomonomethoxine and trimethoprim (2.5:1 ratio). Unlike sulfa drugs biseptol and sulfaton act bactericidal, have a wider spectrum of antimicrobial activity and are effective against strains resistant to sulfanilamide drugs.

In practice, other combinations are also used. sulfa drugs with diaminopyrimidine derivatives. For example, combinations of sulfalene with chloridine are used to treat drug-resistant forms of malaria, and combinations of sulfazine with chloridine are used to treat toxoplasmosis.

Sulfonamides are used to treat infections caused by microorganisms sensitive to these drugs. The choice of drugs is made taking into account the peculiarities of their pharmacokinetics. So, for systemic infections (bacterial infections of the respiratory tract, lungs, bile and urinary tract, etc.) sulfa drugs well absorbed from the gastrointestinal tract. Used to treat intestinal infections sulfa drugs, poorly absorbed from the gastrointestinal tract (sometimes in combination with well-absorbed sulfa drugs).

Single and course doses sulfa drugs, as well as the schemes for their appointment are established in accordance with the duration of action of the drugs. So, sulfa drugs short-acting is used in daily doses of 4-6 G, appointing them in 4-6 doses (course doses 20-30 G); drugs of medium duration of action - in daily doses 1-3 G, appointing them in 2 doses (course doses 10-15 G); long-acting drugs are prescribed in one dose at a daily dose of 0.5-2 G(course doses up to 8 G). Ultra-long-acting sulfonamides are prescribed according to two schemes: daily at the initial dose (on the first day) 0.8-1 G and further in maintenance doses of 0.2 G 1 time per day; 1 time per week at a dose of 1.5-2 G. For children, doses are reduced according to age.

Side effect sulfa drugs manifested by dyspeptic disorders, allergic reactions, neuritis, disorders of the central nervous system. (headache, dizziness, etc.), leukopenia, methemoglobinemia, etc. Due to poor solubility in water sulfa drugs and the products of their acetylation in the body can precipitate in the kidneys in the form of crystals and cause crystalluria (especially when urine is acidified). To prevent this complication when taking sulfa drugs it is advisable to recommend a plentiful alkaline drink.

Contraindicated sulfa drugs if there is a history of data on toxic-allergic reactions to any drugs of this group. For diseases of the liver and kidneys sulfa drugs should be prescribed in reduced doses under control functional state these organs.

Methods of application, doses, forms of release and storage conditions of the main sulfa drugs are given below.

Biseptol(Biseptol; a synonym for Bactrim, Septrin, etc.) is prescribed orally (after meals) for adults and children over 12 years old, 1-2 tablets (for adults) 2 times a day, in severe cases - 3 tablets 2 times a day; children aged 2 to 5 years, 2 tablets (for children); from 5 to 12 years, 4 tablets (for children) 2 times a day. Release form: tablets for adults containing 0.4 G sulfamethoxazole and 0.08 G trimethoprim; tablets for children containing 0.1 G sulfamethoxazole and 0.02 G trimethoprim. Storage: list B.

Salazodimethoxine(Salazodimethoxinum) is used orally (after meals). Adults are prescribed 0.5 G 4 times a day or 1 G 2 times a day for 3-4 weeks. Upon the onset of a therapeutic effect, the daily dose is reduced to 1-1.5 G(by 0.5 G 2-3 times a day). Children aged 3 to 5 years are initially prescribed 0.5 G per day (in 2-3 doses). At the onset of a therapeutic effect, the dose is reduced by 2 times. Children aged 5 to 7 years are initially prescribed 0.75-1 G, from 7 to 15 years, 1-1.5 G per day. Release form: powder, tablets of 0.5 G. Storage: list B; in a place protected from light.

Salazopyridazine(Salazopyridazinum). Methods of application, doses. release forms and storage conditions are the same as for salazodimethoxine.

streptocide(Streptocidum, a synonym for white streptocide) is administered orally to adults at 0.5-1 G at the reception 5-6 times a day; children under the age of 1 year at 0.05-0.1 G, from 2 to 5 years by 0.2-0.3 G, from 6 to 12 years 0.3-0.5 G appointment. Higher doses for adults orally single 2 G, daily 7 G. Topically applied in the form of powders, ointments (10%) or liniments (5%). Release form: powder, tablets of 0.3 and 0.5 G; 10% ointment; 5% liniment. Storage: list B: in a well-closed container.

Streptocid soluble(Streptocidum solubile) is administered intramuscularly and subcutaneously in the form of 1-1.5% solutions prepared in water for injection or isotonic sodium chloride solution, up to 100 ml(2-3 times a day). Intravenously administered in the form of 2-5-10% solutions prepared in the same solvents or 1% glucose solution, up to 20-30 ml. Release form: powder. Storage: List B in well-closed jars.

Sulgin(Sulginum) is prescribed inside for adults 1-2 times a day. G at the reception: on the 1st day 6 times a day, on the 2nd and 3rd days 5 times, on the 4th day 4 times, on the 5th day 3 times a day. The course of treatment is 5-7 days. Other schemes are used to treat acute dysentery. Higher doses adult single 2 G, daily 7 G. release forms: powder; tablets 0.5 G

Silver sulfadiazine(Sulfadiazini argenti) is applied topically. It is part of the Dermazin ointment, which is applied to the burn surface with a layer of 2-4 mm 2 times a day, followed by the imposition of a sterile dressing. Ointment is not prescribed to premature and newborn children; in pregnant women, they are used for health reasons (with burns of more than 20% of the body surface). Release form: tubes of 50 G, cans of 250 G.

Sulfadimezin(Sulfadimezinum; synonymous with sulfadimidine, etc.) is administered orally to adults at the first dose 2 G, then 1 G every 4-6 h(until the body temperature drops), then 1 G after 6-8 h. Children inside at the rate of 0.1 g/kg at the first appointment, then 0.025 g/kg every 4-6-8 h. For the treatment of dysentery, adults are prescribed according to the following scheme: on the 1st and 2nd days, 1 G every 4 h(6 G per day), on the 3rd and 4th days 1 G every 6 h(4 G per day), on the 5th and 6th days 1 G every 8 h(3 G per day). After a break (within 5-6 days), a second cycle is carried out, appointing on the 1st and 2nd days 5 G per day, on the 3rd and 4th days 4 G per day, on the 5th day 3 G per day. For the same purpose, children under 3 years of age are prescribed at the rate of 0.2 g/kg per day (in 4 divided doses) for 7 days, children over 3 years old 0.4-0.75 G(depending on age) 4 times a day. Release form: powder; tablets of 0.25 and 0.5 G

Sulfadimethoxine(Sulfadimethoxinum; synonymous with madribon, etc.) is used orally. Adults are prescribed on the 1st day 1-2 G, in the following days, 0.5-1 G per day (in one dose); children at the rate of 0.025 g/kg on the 1st day and at 0.0125 g/kg in the following days. Release form: powder; tablets of 0.2 and 0.5 G. Storage: list B; in a place protected from light.

Sulfazin(Sulfazinum) is used internally. Adults are prescribed for the 1st appointment 2-4 G, within 1-2 days 1 G every 4 h, in the following days 1 G every 6-8 h; children at the rate of 0.1 g/kg at the first appointment, then 0.025 g/kg every 4-6 h. Release form: powder; tablets 0.5 G. Storage: list B; in a place protected from light.

Sulfalen(Sulfalenum; synonymous with kelfisin, etc.) is prescribed by mouth for adults, 2 G once every 7-10 days or on the first day 1 G, then by 0.2 G daily. Release form: tablets of 0.2 G. Storage: list B.

Sulfamonomethoxine(Sulfamonomethoxin). The method of administration and doses are the same as those of sulfadimethoxine. Release form: powder; tablets 0.5 G

Sulfapyridazine(Sulfapyridazinum; synonym: spofazadin, sulamine, etc.). The method of administration and doses are the same as those of sulfadimethoxine. Release form: powder; tablets 0.5 G. Storage: list B; in a place protected from light.

Sulfatone(Sulfatonum) is prescribed by mouth for adults, 1 tablet 2 times a day. Higher doses for adults: single - 4 tablets, daily - 8 tablets. Release form: tablets containing 0.25 G sulfamonomethoxine and 0.1 G trimethoprim. Storage: list B; in a dry, dark place.

Sulfacyl sodium(Sulfacylum-natrium; synonym: soluble sulfacyl, sulfacetamide-sodium, etc.) is administered orally to adults at 0.5-1 G, children 0.1-0.5 G 3-5 times a day. Intravenously (slowly) 3-5 ml 30% solution 2 times a day. In eye practice, they are used in the form of 10-20-30% solutions and ointments. Higher doses for adults orally single 2 G, daily 7 G. Release form: powder; 30% solution for injection in ampoules of 5 ml; 30% solution in vials of 5 and 10 ml; 20% and 30% solutions (eye drops) in dropper tubes of 1.5 ml; 30% ointment 10 G. Storage: list B; in a cool, dark place.

Urosulfan(Urosulfanum) is used internally. Adults are prescribed in the same doses as sodium sulfacyl, children 1-2.5 G per day (in 4-5 doses). The higher daily doses for adults are the same as sodium sulfacyl. Release form: powder, tablets of 0.5 G

Phtazin(Phthazinum) is administered orally to adults on the first day, 1 G 1-2 times, in the following days, 0.5 G 2 times a day. For children, the dose is reduced according to age. Release form: powder; tablets 0.5 G. Storage: list B: in a place well protected from light.

Ftalazol(Phthalazolum; synonymous with phthalyl-sulfathiazole, etc.) is used orally for dysentery. Adults are prescribed on the 1-2nd day 1 G every 4 h(6 G per day), on the 3rd-4th days, 1 G every 6 h(4 G per day), on the 5-6th day, 1 G every 8 h(3 G per day). After 5-6 days, the treatment is repeated: on the 1st-2nd days - 5 G per day, on the 3rd-4th days - 4 G per day, on the 5th day - 3 G per day. For other intestinal infections, adults are prescribed in the first 2-3 days 1-2 G, in the following days, 0.5-1 G every 4-6 h. Children under 3 years old with dysentery are prescribed at the rate of 0.2 g/kg per day (in 3 divided doses), children over 3 years old 0.4-0.75 G at the reception 4 times a day. The highest oral doses for adults are the same as for sulfacyl sodium. Release form: powder; tablets 0.5 G. Storage: list B; in a well sealed container.

Etazol(Aethazolum; synonymous with sulfaetidol, etc.) is administered orally to adults, 1 G 4-6 times a day: children under 2 years old 0.1-0.3 G every 4 h, from 2 to 5 years - 0.3-0.4 G every 4 h, from 5 to 12 years old - 0.5 each G every 4 h. Locally prescribed in the form of a powder (powder) or ointment (5%). The highest oral doses for adults are the same as for sulfacyl sodium. Release form: powder; tablets of 0.25 and 0.5 G. Storage: list B; in a well sealed container.

Etazol sodium(Aethazolum-natrium; synonymous with etazol soluble) is administered intravenously (slowly) 5-10 ml 10% or 20% solution. In pediatric practice, the drug is used orally in granules, which are dissolved in water before use and prescribed to children at the age of 1 year - 5 ml (0,1 G), 2 years - 10 ml (0,2 G), 3-4 years - 15 ml (0,3 G), 5-6 years - 20 ml every 4 h. Release form: powder; ampoules of 5 and 10 ml 10% and 20% solutions; granules in bags of 60 G. Storage: list B; in a well-closed container, protected from light.

International name: Sulfadiazine (Sulfadiazine)

Dosage form:

Pharmachologic effect:

Indications:

Kelfizin

International name: Sulfalene (Sulfalene)

Dosage form: solution for intravenous and intramuscular administration, tablets

Pharmachologic effect: Antimicrobial bacteriostatic agent, ultra-long-acting sulfanilamide. The mechanism of action is due to competitive antagonism ...

Indications: Infections caused by susceptible microorganisms: pneumonia, bronchitis, gonorrhea, sepsis, toxoplasmosis, sinusitis, otitis media, inflammatory diseases...

mafenide acetate

International name: Mafenide (Mafenide)

Dosage form: ointment for external use

Pharmachologic effect: Mafenide acetate is a sulfanilamide, a broad-spectrum antimicrobial drug, active in vitro against gram-positive and gram-negative ...

Indications: Infected burns, purulent wounds, bedsores, trophic ulcers.

norsulfazol

International name: Sulfathiazole (Sulfathiazole)

Dosage form: tablets

Pharmachologic effect:

Indications: Infections caused by susceptible microorganisms: diseases of the respiratory and biliary tract.

Salazodimethoxine

Dosage form: tablets

Pharmachologic effect: Antibacterial agent, has an anti-inflammatory effect. It breaks down in the intestine, forming 5-aminosalicylic acid and sulfadimethoxin, ...

Indications: Nonspecific ulcerative colitis, Crohn's disease; rheumatoid arthritis(basic therapy).

Silvederm

International name: Sulfadiazine (Sulfadiazine)

Dosage form: topical aerosol, topical cream, topical ointment

Pharmachologic effect: Sulfanilamide drug for topical use. It has a wide spectrum of antibacterial action, which includes almost all microorganisms, ...

Indications: Infected superficial wounds and burns with weak exudation, bedsores, trophic and long-term non-healing ulcers (including stump wounds), abrasions, skin grafting.

Silverdin

International name: Sulfadiazine (Sulfadiazine)

Dosage form: topical aerosol, topical cream, topical ointment

Pharmachologic effect: Sulfanilamide drug for topical use. It has a wide spectrum of antibacterial action, which includes almost all microorganisms, ...

Indications: Infected superficial wounds and burns with weak exudation, bedsores, trophic and long-term non-healing ulcers (including stump wounds), abrasions, skin grafting.

streptocide

International name:

Dosage form:

Pharmachologic effect: Antimicrobial bacteriostatic agent, sulfanilamide. The mechanism of action is due to competitive antagonism with PABA, inhibition of dihydropteroate synthetase, ...

Indications:

Streptocid soluble

International name: Sulfanilamide (Sulfanilamide)

Dosage form: liniment, topical ointment, topical powder, tablets

Pharmachologic effect: Antimicrobial bacteriostatic agent, sulfanilamide. The mechanism of action is due to competitive antagonism with PABA, inhibition of dihydropteroate synthetase, ...

Indications: Local treatment: tonsillitis, infected wounds of various etiologies, burns (stage I-II), folliculitis, furuncle, carbuncle, acne vulgaris, impetigo, other purulent-inflammatory processes of the skin, erysipelas.