1. Crystalluria - microcrystals fall out in the tubules of the kidneys due to the poor solubility of drugs, especially acetylated derivatives. Most often cause crystalluria norsulfazol, sulfadimezin. Do not cause crystalluria sulfadimethoxine and urosulfan.
2. Allergic reactions in 5-10%, more often in the form of fever, red rash (spots) on the skin.
3. Inhibition of hematopoiesis with the development of leukopenia, agranulocytosis, thrombocytopenia.
4. Hemolytic anemia.
5. Photosensitization.
6. Neuropsychiatric disorders (fatigue, headache, paresthesia, myalgia, neuritis, dizziness, convulsions).
7. Dysbacteriosis, hypovitaminosis B 1, B 2, PP, B 6, B 12, pantothenic acid.
8. The formation of methemoglobin, the development of hypoxia, acidosis, cyanosis, the formation of sulfohemoglobin. For prevention - reducing agents and antioxidants - vitamins C and E, glucose.
9. Possible inhibition of the function of the sex glands and the thyroid gland.
Combined sulfonamides
Bactrim(biseptol, co-trimoxazole, septrin) contains sulfamethoxazole, trimethoprim.
The mechanism of antibacterial action is a double blockade of the synthesis of tetrahydrofolic acid. This leads to the fact that Bactrim, unlike sulfonamides, has a bactericidal effect, the spectrum of antimicrobial action is wider, it has a pronounced antibacterial effect in many infections resistant to other drugs.
The drug is rapidly absorbed from the gastrointestinal tract, penetrates well into organs and tissues. It is effective for infections of the bronchopulmonary, digestive, urinary systems, meningitis, surgical infections, for the prevention of purulent-septic complications in surgery.
The drug is prescribed 2 tablets 2 times a day after meals (in the morning
and in the evening).
Side effects: nausea, vomiting, anorexia, diarrhea, skin-allergic reactions: erythematous rash, urticaria, itching; oppression of hematopoiesis (leukopenia, megaloblastic anemia); sometimes there is a violation of the function of the liver, kidneys.
With prolonged use of Bactrim, it is necessary to control the composition of peripheral blood. Do not prescribe the drug to children under 6 years of age.
Nitrofurans
The drugs have a bactericidal effect due to damage to the microbial cell wall, irreversible oxidation of NADH to NAD +, inhibition of the tricarboxylic acid cycle and the formation of acetyl-CoA. Resistance to nitrofurans develops slowly.
Nitrofurans are effective against gram-positive and gram-negative microbes, as well as some large viruses, Trichomonas, Giardia. In some cases, they retard the growth of microorganisms resistant to sulfonamides and antibiotics. The drugs reduce the production of bacterial toxins, increase the body's resistance.
Furadonin- acts on staphylococci, streptococci, Escherichia coli, causative agents of typhoid, paratyphoid, dysentery, Proteus bacillus.
When taken orally, it is rapidly and actively absorbed, excreted in a significant amount by the kidneys, where bactericidal concentrations of the drug are created. Therefore, the drug is especially effective in urinary tract infections, it is also used to prevent infection during urological manipulations. Assign inside after eating.
Furagin- has a wide antimicrobial spectrum. It is prescribed for infections of the kidneys and urinary tract, sometimes for infectious and inflammatory diseases of the respiratory tract. Apply inside after meals. Locally used for washing and douching in surgery and gynecology (solution 1:13000). In ophthalmology - eye drops (solution 1:13000). Can be used with dicaine solution.
Side effects: in some cases, they can cause loss of appetite, heartburn, nausea, and sometimes vomiting; allergic reactions are possible.
To prevent side effects when taking nitrofuran derivatives, it is recommended to drink plenty of fluids, antihistamines, vitamins (nicotinic acid, thiamine bromide). To reduce the inhibition of hematopoiesis, folic and ascorbic acids give a good effect.
Sulfanilamide has a chemical similarity to PABA. Sulfanilamide enters the microbial cell, prevents the incorporation of PABA into dihydrofolic acid, and also competitively inhibits the microorganism's enzyme dihydropteroate synthetase (responsible for incorporating PABA into dihydrofolic acid). These processes lead to a disruption in the formation of dihydrofolic acid, the formation of tetrahydrofolic acid from it, which is necessary for the formation of pyrimidines and purines, decreases, and the development and growth of microorganisms stops. Sulfanilamide is active against gram-negative and gram-positive cocci (including streptococci, meningococci, pneumococci, gonococci), Shigella spp., Escherichia coli, Vibrio cholerae, Bacillus anthracis, Clostridium perfringens, Yersinia pestis, Corynebacterium diphtheriae, Chlamydia spp., Toxoplasma gondraelii, Actieli . When used topically, sulfanilamide promotes rapid healing of wounds.
After oral administration, it is rapidly absorbed in the gastrointestinal tract. The maximum concentration in the blood is reached after 1-2 hours and decreases by 50%, usually in less than 8 hours. Sulfanilamide passes through tissue barriers, including the blood-brain and placental barriers. Sulfanilamide is distributed throughout the tissues and after 4 hours is determined in the cerebrospinal fluid. In the liver, sulfanilamide is metabolized to form inactive metabolites. It is excreted mainly by the kidneys (90-95%).
There is no information on the effect on fertility and mutagenic, carcinogenic effects with prolonged use in humans and animals. Previously, for the treatment of tonsillitis, cystitis, erysipelas, enterocolitis, pyelitis, treatment and prevention of wound infection, sulfanilamide was taken orally. In the past, sulfanilamide was used in the form of 5% aqueous solutions for intravenous administration, which were prepared ex tempore. Now sulfanilamide is used only externally in the form of liniment.
Indications
Locally: purulent-inflammatory skin lesions, tonsillitis, infected wounds of various origins (including cracks, ulcers), pyoderma, furuncle, folliculitis, carbuncle, erysipelas, impetigo, acne vulgaris, burns (1 and 2 degrees).
Dosage and administration of sulfanilamide
Sulfanilamide is used topically. For deep wounds, sulfanilamide in the form of a carefully ground sterilized powder (5–10–15 g) is injected into the wound cavity, antibacterial drugs are administered orally together. For superficial infectious diseases of the mucous membranes of the nose and ear and skin, for ulcers, burns, it is used in the form of 5% liniment, 10% ointment or powder; ointment or liniment is smeared on a gauze napkin or applied directly to the affected surface; dressings are made in 1-2 days. In a mixture with sulfathiazole, ephedrine and benzylpenicillin, sulfanilamide is sometimes used topically (for acute rhinitis) in the form of a powder, drawing or blowing it into the nasal cavity when inhaling.
With prolonged use, periodic monitoring of peripheral blood is necessary.
Contraindications for use
Hypersensitivity (including to other sulfonamides and sulfonamides), anemia, diseases of the hematopoietic system, hepatic / renal failure, porphyria, azotemia, congenital deficiency of glucose-6-phosphate dehydrogenase, lactation, pregnancy.
Application restrictions
There is no data.
Use during pregnancy and lactation
The use of sulfanilamide is contraindicated during pregnancy and lactation. Sulfanilamide with systemic absorption can quickly cross the placenta and be found in the fetus in the blood, as well as cause toxic reactions. The safety of sulfonamide use during pregnancy has not been established. It is not known whether sulfonamide has harmful fetal effects when used by women during pregnancy. In experiments in mice and rats treated with sulfanilamide, the incidence of cleft palate and other fetal bone malformations increased. Sulfanilamide is excreted in breast milk, in newborns it can cause kernicterus.
Side effects of sulfanilamide
allergic reactions; with prolonged use topically in large quantities, a systemic effect is possible: dizziness, headache, paresthesia, nausea, tachycardia, dyspepsia, vomiting, agranulocytosis, leukopenia, cyanosis, crystalluria.
Interaction of sulfanilamide with other substances
Myelotoxic drugs increase the hematotoxicity of sulfanilamide.
Sulfonamides are derivatives of sulfanilic acid amide (para-aminobenzenesulfamides), a structural analogue of para-aminobenzoic acid (PABA) (Fig. 18.2). PABA is a substrate for the synthesis of nucleic acids in a microbial cell. As a result of this structural similarity, sulfonamides disrupt the synthesis of nucleic acids in many microorganisms, which provides the antimicrobial effect of these drugs. Sulfonamides became the first broad-spectrum chemotherapeutic antimicrobial agents for systemic use: in the figurative expression of some scientists, sulfonamides became the "first magic drugs that changed medicine", significantly reduced the incidence and mortality from many infections. Long-term, more than 70 years of clinical use, many microorganisms, previously sensitive to the action of sulfonamides, have developed resistance to these antimicrobial agents. This reduced the clinical significance of sulfonamides, limited their use mainly to urinary tract infections. Since the mid-1970s, some sulfonamides have been used as combined preparations with benzylpyrimidinams, which also disrupt the synthesis of nucleic acids, in particular with trimethoprim. This combination is synergistic and expands the spectrum of action and indications for the use of combined drugs.
Rice. 18.2. Chemical structure of sulfonamides
History reference. In 1932, German scientists working in the Farbenindustry concern, Joseph Klarer and Fritz Mitch, synthesized the red dye streptozone, or red streptocide, which was subsequently patented under the name prontosil. The prominent German microbiologist Domagk (1895-1964), who headed the laboratory of the Bayer pharmaceutical concern, discovered that this dye saved mice from a 10-fold lethal dose of hemolytic streptococcus and pathogens of other infections. It was found that in vitro Prontosil had no effect on bacteria, but after being introduced into the body of mice, it protected them from imminent death. Subsequently, an explanation was found for this contradiction - prontosil is cleaved in the body to form sulfonamides.
The scientist conducted the first clinical trial of prontosil on his own child. Domagk's daughter Hildegard injured her finger and developed sepsis, which was fatal at the time. In desperation, Domagk was forced to give his daughter prontosil, which was not yet registered, and quickly contributed to the girl's recovery. The powerful antimicrobial action of prontosil was reported by Domagk in the journal "Deutsche Medizinische Wochenschrift" in 1935 in the article "Contribution to the Chemotherapy of Bacterial Infections". G. Domagk's discovery was highly appreciated by the world scientific community. In 1939, the scientist was awarded the Nobel Prize in Physiology or Medicine for the discovery of the antibacterial effect of prontosil, but by order of Hitler, German citizens were forbidden to receive Nobel Prizes. Domagk was arrested, spent some time in the Gestapo and was forced to refuse the Nobel Prize. Domagk received the medal and diploma of the Nobel laureate only in 1947 without monetary reward, which, according to the rules, was returned to the reserve bonus fund.
Classification of sulfa drugs according to pharmacokinetic characteristics:
1. Sulfonamides for resorptive action, which are well absorbed in the gastrointestinal tract.
1.1. Short acting (half-life less than 6:00) - sulfanilamide (streptocid, or white streptocide) sulfadimidine (sulfadimezin).
1.2. Intermediate-acting sulfonamides (half-life less than 10:00): sulfamethoxazole, is part of the combination drug co-trimoxazole .
1.3. Long-acting (half-life 24-28 hours) - Sulfadimethoxine .
1.4. Increased action (half-life more than 48 hours) - sulphate .
2. Sulfonamides are poorly absorbed and act in the intestines: ftalazol .
3. Sulfonamides for local use: Sulfacetamide (sulfacyl sodium), silver sulfazine (sulfargin), silver sulfadiazine (dermazine).
Gerhard Johannes Paul Domagk (1895-1964 pp.)
4. Combined preparations of sulfonamides.
4.1. With salicylic acid: salazosulfapyridine (sulfasalazine), salazodimethoxine .
4.2. With trimethoprim: biseptol (co-trimoxazole, bactrim) .
Pharmacokinetics of sulfonamides. Sulfonamides are well absorbed in the alimentary canal, while long-acting sulfonamides are slower than short-term ones. They create high concentrations of drugs in the blood, 20 to 90% of sulfonamides bind to plasma proteins. At the same time, sulfonamides displace other substances from proteins, in particular bilirubin, therefore, with hyperbilirubinemia, these drugs are not prescribed. Widely distributed in tissues and body fluids, including cerebrospinal fluid (with the exception of sulfadimethoxine). Bacteriostatic concentrations of sulfonamides are created in the lungs, liver, kidneys, as well as in pleural, ascitic, synovial fluids and bile. The duration of action is also determined by the intensity of reabsorption of drugs in the kidneys: sulfadimethoxine is reabsorbed by more than 90%, a high degree of reabsorption is also characteristic of sulfalene.
Metabolized sulfonamides mainly in the liver by acetylation or glucuronidation. Acetylated sulfonamides are poorly soluble in water, therefore, when excreted by the kidneys, especially in the presence of an acidic urine environment, they form crystals. To prevent calculus formation and increase the solubility of sulfonamides, it is necessary to create an alkaline urine reaction by prescribing hydrocarbonate mineral waters (alkaline drink) to patients. It is not advisable to consume acidic foods (acidic fruits and vegetables, juices) during treatment with sulfonamides.
Conclusion sulfonamides is carried out by the kidneys. Usually in the urine the concentration of drugs is 10-20 times higher than in the blood. If the excretory function of the kidneys is impaired, the dose of sulfonamides should be reduced, and in case of renal failure, sulfonamides are contraindicated.
Pharmacological sulfa drugs.
Sulfonamides have a bacteriostatic effect on microorganisms.
The spectrum of action of sulfonamides:
1. Bacteria - gram-positive cocci (streptococci) and gram-negative cocci (meningococci), Escherichia coli, shigella, vibrio cholerae, clostridia, anthrax, diphtheria.
2. Chlamydia - causative agents of trachoma and ornithosis, nocardia, pneumocystis.
3. Actinomycetes (paracoccidioids).
4. The simplest - the causative agents of toxoplasmosis and malaria.
Preparations containing silver - silver sulfazine (sulfargin), silver sulfadiazine (dermazin), active against many pathogens of wound infections.
The mechanism of action of sulfonamides - a typical example competitive antagonism. Sulfonamides are transported into the bacterial cell by the same transporters that carry PABA, which, accordingly, reduces the number of free PABA carriers. Subsequently, sulfonamides compete with PABA for the active center of the dihydropteroate synthetase enzyme, enter into a reaction to form dihydropteroic acid, forming non-functional analogues of folic acid. The further synthesis of purines and pyrimidines and the growth and reproduction of bacteria are blocked (Fig. 18.3). Due to the fact that in the cells of the macroorganism there is no synthesis of folic acid, but only the utilization of dihydrofolic acid, the drugs do not affect the formation of purines and pyrimidines in the patient's body.
Rice. 18.3. Mechanisms of action of antimicrobial synthetic chemotherapeutic agents
The affinity of the receptors and enzymes of most microorganisms for nilamid sulfate is less than the affinity for PABA, therefore, to inhibit the growth of microbes, significantly higher concentrations of sulfonamides are required than PABA. When treating with sulfonamides, at the beginning of the course of treatment, it is necessary to apply shock (loading) doses of drugs, and then constantly maintain high concentrations of drugs (principle of rational sulfannlamidotherapy).
The antimicrobial effect of sulfonamides is inhibited by drugs that are chemically derived from PABA (for example, novocaine, novocainamide). The pharmacological effect of drugs also decreases in the wound in the presence of inflammation, manure and tissue destruction, due to the presence of high concentrations of PABA.
Indications for the use of sulfonamides.
I. Ingestion of resorptive sulfonamides:
1.1. Treatment of infections of the urinary and biliary tract.
1.2. Prevention of meningococcal infection.
1.3. Treatment of infections caused by nocardia.
1.4. With paracoccidioidomycosis.
1.5. Treatment of toxoplasmosis and malaria.
1.6. With trachoma and ornithosis.
1.7. Plague prevention.
II. Local application:
2.1. For the treatment of bacterial conjunctivitis in the auxiliary treatment of trachoma, as well as for their prevention, including for the prevention of gonorrheal blepharitis (blennorea) in newborns, sulfacetamide (sulfacyl sodium) is used in the form of 30% or 20% solutions and 30% eye ointments.
2.2. Silver salts of sulfonamides are used topically in the form of ointments, creams for burns, trophic ulcers and bedsores.
Side effects of sulfonamides.
1. Allergic reactions - frequent complications, especially frequent skin rash, sometimes with fever. Rarely - more dangerous effects, in particular Stevens-Johnson syndrome (erythema multiforme with a high mortality rate), toxic epidermal necrolysis (Lyell's syndrome) - necrosis of all layers of the skin with their exfoliation, damage to internal organs and frequent (25%) death.
2. crystalluria with damage to the renal tubules and the appearance of symptoms of renal colic.
3. Damage to blood cells ( hematopoietic disorder) - leukopenia, agranulocytosis, aplastic and hemolytic anemia (the latter develops with congenital deficiency of glucose-6-phosphate dehydrogenase). It is necessary to control the blood picture when taking sulfonamides.
4. Bilirubin encephalopathy - hyperbilirubinemia in newborns.
5. Dysbacteriosis.
6. Photosensitive reactions.
Combined preparations of sulfonamides with other drugsCombination of sulfonamides with benzylpyrimidine derivatives Benzylpyrimidines - trimethoprim and pyrimethamine- violate the next step in the synthesis of nucleic acids. They block dihydrofolate reductase, which disrupts the further synthesis and metabolism of proteins. The human analogous enzyme is resistant to these agents. Benzylpyrimidines have a higher lipophilicity and are better distributed in the tissues of the body than sulfonamides, therefore, in a combined preparation, 5 parts of sulfonamides per 1 part of trimethoprim, and 20 parts of sulfonamides per 1 part of pyrimethamine.
Trimethoprim is a weak base and concentrates in prostatic and vaginal fluids, which are acidic, allowing it to exhibit greater antibacterial activity in these environments than other antimicrobials.
High concentrations of trimethoprim in the urine (100 mg orally every 12 hours) are susceptible to most microorganisms. The drug can be used as a monotherapy in the presence of acute urinary tract infections.
Certain microorganisms can be resistant to benzylpyrimidines, for example, some bacteria of the intestinal group, Haemophilus other.
Side effects. Benzylpyrimidines, like other antifolate drugs, cause side effects associated with folic acid deficiency - megaloblastic anemia, leukopenia, agranulocytosis. Antidote benzylpyrimidine - folic acid, which must be prescribed to patients after the start of the use of benzylpyrimidine to prevent the toxic effects of the latter on the cells of the hematopoietic system. High doses of trimethoprim cause hyperkalemia.
Combined preparations simultaneously act on two enzymes for the synthesis of nucleic acids and have a larger spectrum and a bactericidal type of action.
Combination of sulfonamides with trimethoprim - co-trimoxazole (biseptol , buck-der). Contains a medium-acting sulfonamide sulfamethoxazole and trimethoprim .
Indications for use. Biseptol is the drug of choice for the treatment of pneumocystis pneumonia, toxoplasmosis; shigellous enteritis; salmonella infections resistant to ampicillin and chloramphenicol; otitis media; complicated infections of the lower and upper urinary tract; prostatitis, listeriosis, chancroid, melioidosis. It is a second-line drug in the treatment of infections caused by Staphylococcus aureus. The drug is prescribed 2 tablets twice a day every 12 hours. Such doses may be sufficient for long-term inhibition of chronic urinary tract infections. As a means of chemoprophylaxis of recurrent (recurrent) urinary tract infections (especially in women to prevent postcoital infection), 1 tablet 2 times a week can be used for many months.
Combination of sulfonamides with pyrimethamine - sulfasalazine (salazosulfa-pyridine) breaks down to 5-aminosalicylic acid and sulfapyridine (sulfanilamide is slowly absorbed from the intestine) The drug is broken down in the intestine to salicylic acid, which has an anti-inflammatory effect, and the corresponding sulfonamides, which allows the treatment of chronic inflammatory diseases of the colon (ulcerative colitis, Crohn's disease). Otherwise, salicylic acid is difficult to deliver to the lower intestines without damaging the gastric mucosa.
Indications for use. Moderate ulcerative colitis, chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease (granulomatous colitis), etc.).
Sulfonylsporidneni drugs. sulfones
Sulfones are the main drugs for the treatment of leprosy (leprosy). In this disease, anti-tuberculosis antibiotics of the rifamycinam group and fluoroquinolones, which are used in combination with sulfone, are also effective.
to them The drug is taken orally. Diaphenylsulfone exhibits a bacteriostatic type of action. For many years it has been used to treat all forms of leprosy, but its irregular and inadequate use (mototherapy) has led to the development of resistance - both primary and secondary. Diaphenylsulfone is also used for the treatment of dermatitis herpetiformis, the prevention of pneumocystis pneumonia.
Dapsone causes allergic reactions such as erythema nodosum leprosy.
drugs
|
Name of the drug |
release form |
mode of application |
|
Sulfacyl sodium Sulfacylum sodium |
20% and 30% eye drops in 5 or 10 ml vials, 1 ml in dropper tubes |
Instill 2-3 drops 5-6 times a day into the conjunctival sac of the affected eye. For the prevention of blennorrhea in newborns, instill 2 drops in both eyes immediately after birth and 2 drops after 2 hours |
|
ftalazol |
Tab. 0.5 g each |
Inside in the first 2-3 days, 1-2 g every 4-6 hours, in the next 2-3 days - 0.5-1 g every 4-6 hours |
|
sulfadimethoxine Sulfadimethoxinum |
Tab. 0.5 g each |
Inside 1 time per day on the first day, 1-2 g, on subsequent days, 0.5-1 g with intervals between doses of 24 hours |
|
dermazin |
1% cream in tubes of 50 g |
Apply to burn surfaces 1 time per day in severe cases - 2 times a day, observing sterility |
|
sulfasalazine |
Tab. in a shell of 0.5 g |
1-2 g 4 times a day with meals |
|
Biseptol |
Tab. for adults, 0.48 g (480 mg - tab. for adults); 0.96 g (960 mg - tab. Forte) and 0.12 g (120 mg - tab. For children) |
2 tablets of 480 mg 2 times a day |
27493 0
Sulfonamides are broad-spectrum bacteriostatic drugs, competitive antagonists of para-aminobenzoic acid (PABA), which is necessary for most microorganisms to synthesize folic acid. They bind pterin and inhibit folate synthetase, resulting in a bacteriostatic effect.
The antimicrobial properties of sulfanilamide preparations are significantly (20-100 times) potentiated and approach bactericidal action when combined with trimethoprim, which is a specific inhibitor of bacterial folate reductase. It should be taken into account that in environments with a high content of PABA, for example, in the focus of purulent fusion of tissues, the antimicrobial activity of sulfonamides is sharply reduced.
The spectrum of antimicrobial activity of sulfa drugs includes:
- gram-positive microorganisms (streptococci, staphylococci, clostridia, anthrax, actinomycetes). It should be noted that at present a significant number of strains of staphylococci have acquired resistance to these drugs;
- Gram-negative microorganisms (E. coli, Shigella, Salmonella, Haemophilus influenzae, bacteroids, Vibrio cholerae, meningococci, gonococci, chlamydia - causative agents of urogenital infections);
- protozoa (plasmodia malaria, toxoplasma, trypanosomes).
The spectrum of action of drugs combined with trimethoprim approaches the spectrum of action of the antibiotic chloramphenicol. Up to 50-90% of strains of staphylococci, E. coli, enterobacteria, salmonella, shigella, pseudomonads are sensitive to them.
When taken systemically, sulfa drugs can cause dyspeptic symptoms (nausea, vomiting), headache, allergic reactions (rash, dermatitis, fever). With prolonged use, the development of leukopenia, thrombocytopenia, agranulocytosis is possible. A likely side effect is the precipitation of crystals in the kidneys (especially for the drugs sulfadimezin, norsulfazol, sulfapiridazine, sulfamonomethoxine). The danger of crystalluria is greatly reduced by using an alkaline drink. Therefore, it is advisable to simultaneously prescribe alkaline mineral waters or sodium bicarbonate (up to 5-10 g per day).
The toxicity of preparations combined with trimethoprim is higher than that of monocomponent agents, especially in folate-deficient conditions (diseases of the hematopoietic organs, pregnancy, old age).
General classification of sulfa drugs
Drugs well absorbed from the gastrointestinal tract:
A) short-term action: streptocide (sulfanilamide, white streptocide); sulfadimezin (sulfadimidine); etazol (sulfaetidol); norsulfazol (sulfathiazole); urosulfan (sulfa-carbamide);
B) medium duration of action: sulfazine (sulfadiazine); sulfamethoxazole;
C) long-acting: sulfadimethoxine; sulfapyridazine (sulfamethoxypyridazine); sulphamonomethoxine;
D) ultra-long action: sulfalene; sulfalene-meglumine.
Drugs that are poorly absorbed from the gastrointestinal tract (acting in the intestinal lumen): ftalazol (phthalyl-sulfathiazole); sulgin (sulfaguanidine); phthazine (phthalylsulfapyridazine); salazopyridazine (salazodin); salazosulfapyridine (sulfasalazine, salazopyrin).
Topical preparations: sulfacyl sodium (sulfaietamide); silver sulfadiazine (dermazin, flamazin).
IV. Combined sulfa drugs:
A) preparations containing sulfamethoxazole and trimethoprim: Co-trimoxazole (bactrim, biseptol, berlocid, septrin, groseptol);
B) preparations containing sulfadimezin and trimethoprim: proteseptil (potesetta);
C) preparations containing sulfamonomethoxin and trimethoprim: sulfatone.
In dentistry, sulfanilamide drugs are used for various inflammatory diseases of the pulp, periodontium, and for the prevention of infectious complications after surgery. These indications include:
— pharmacotherapy of deep caries. Streptocid and norsulfazol, together with antibiotics and enzymes, are part of the pastes for covering the bottom of the carious cavity before filling;
- pharmacotherapy of pulpitis with a biological method of treatment;
- covering the pulp stump during amputation in the surgical treatment of pulpitis (norsulfazol or streptocide in combination with antibiotics monomycin or neomycin);
- acute periodontitis (30% solution of albucid together with antibiotics and antiseptics);
- periodontitis of milk teeth (pastes with norsulfazole, astringents and enzyme preparations for filling the root canals of milk teeth);
- treatment of acute odontogenic infection (locally - 30% sodium sulfacyl solution; systemically - any sulfanilamide well absorbed in the intestine, for 5-7 days);
- treatment of periodontal disease (pastes and emulsions with sulfonamides for the treatment of pathological periodontal pockets);
- aphthous and ulcerative stomatitis (30% solution of sodium sulfacyl for irrigation of aphthae and ulcerative surface).
Ingalipt(Inhalyptum).
pharmachologic effect: is a combined preparation containing soluble streptocide - 0.75 g, thymol, eucalyptus oil and peppermint oil - 0.015 g each, ethyl alcohol 95% - 1.8 g, sugar - 1.5 g, glycerin - 2.1 g , tween-80 - 0.9 g, water - up to 30 ml. It has an antiseptic and anti-inflammatory effect.
Indications: used for infectious and inflammatory lesions of the oral mucosa and periodontal tissues (aphthous and ulcerative stomatitis, ulcerative necrotic gingivitis).
Mode of application: irrigation of the oral mucosa. Before irrigation, it is recommended to rinse your mouth, remove plaque from erosive surfaces. In the oral cavity should be held for 5-7 minutes; irrigation to produce 34 times a day.
Side effect: Allergic reactions are possible.
Release form: aerosol cans containing 30 ml of the drug.
Storage conditions: at temperatures from +3 to +35°C.
Co-trimoxazole(Co-Trimoxazole). Synonyms: Bactrim (Bactrim), Sinersul (Sinersul), Biseptol (Biseptolitm), Berlocid (Veglocid), Groseptol (Groseptol), Septrin (Septrin), Sumetrolim (Sumetrolim).
pharmachologic effect: is a combined preparation containing sulfamethoxazole and trimethoprim in a 5:1 ratio. Both drugs have a bacteriostatic effect. In combination, they provide a pronounced bactericidal effect against gram-positive and gram-negative microbes, including those resistant to sulfanilamide preparations. The drug is effective against coccal flora, but ineffective against Pseudomonas aeruginosa, spirochetes.
Indications: used for surgical infections.
Mode of application: appoint inside. A tablet for adults contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim, for children - 100 and 20 mg, respectively. Recommended dosage: adults and children over 12 years old, 2 tablets 2 times a day after meals, for chronic infections - 1 tablet 2 times a day. Children from 2 to 5 years old are recommended for a single dose of 2 tablets (0.12 g each), 5-12 years old - 4 tablets 2 times a day. The course of treatment is 5-14 days.
Side effect: possible nausea, vomiting, diarrhea, allergic reactions, nephropathy, leukopenia, agranulocytosis. : see Streptocide.
Contraindications: similar to those of long-acting sulfa drugs. Limit use in young children. Do not use in pregnant women, with diseases of the hematopoietic system.
Release form: tablets of 0.12 and 0.48 g, in a package of 20 pcs (each tablet contains 100 mg of sulfamethoxazole and 20 mg of trimethoprim or 400 mg and 80 mg, respectively); forte tablets, in a package of 10 pcs (content of sulfamethoxazole and trimethoprim 800 mg and 160 mg); 100 ml syrup in a vial complete with a dosing spoon (5 ml of syrup contains 200 mg of sulfamethoxazole and 40 mg of trimethoprim).
Storage conditions: list B.
Sulfadimethoxine(Sulfadimethoxin).
According to the pharmacological action, Indications m, method of administration and side effects similar to sulfapyridazine.
Interaction with other drugs: can be combined with antibiotics of the penicillin group, erythromycin. See: Streptocid, Norsulfazol, Sulfapyridazine.
Release form: powder, tablets of 0.2 and 0.5 g.
Storage conditions: list B.
Sulfanilamide(Sulfanilamide). Synonym: Streptocide (Streptocidum).
pharmachologic effect: is an antimicrobial drug that is active against cocci (streptococcus, meningococcus, pneumococcus, gonococcus), as well as coli coli. Recently, many types of staphylococci are resistant.
Indications: in dentistry, it is used topically in the treatment of infected ulcers of the oral mucosa or infected wounds of the maxillofacial region.
Mode of application: in dentistry, they are mainly used topically in the form of a powder, ointment or liniment. Apply to the affected surface or injected into the wound 5-15 g of sterile powder. It is rarely used systemically.
Side effect: when applied topically in conditions of sensitization, allergic reactions are possible. With systemic use: nausea, vomiting, diarrhea, allergic skin reactions, impaired leukopoiesis.
Interaction with other drugs: combined use with acids, hexamethylenetetramine, adrenaline solution is impractical, as they are chemically incompatible. When combined with esters of para-aminobenzoic acid (novocaine, anestezin, dikain), the antibacterial activity of streptocide decreases by a competitive mechanism.
Contraindications: for topical use - a known allergy to sulfonamides. For systemic use - hypersensitivity to sulfonamides, pregnancy, lactation, blood diseases. Systemically, it should be prescribed with caution in diseases of the liver, kidneys (dynamic monitoring of liver and kidney function is necessary).
Release form: powder, ointment 5 and 10% in glass jars, liniment 5% in glass jars or tubes.
Storage conditions: in a cool, dark place.
Sulfapyridazine(Sulfapyridazinum), Synonym: Sulfamethoxypyridazine.
pharmachologic effect: long-acting sulfanilamide drug with antibacterial activity against gram-positive (streptococcus, pneumococcus, staphylococcus, enterococcus) and gram-negative (E. coli, Proteus, etc.) microbes, some protozoa. Does not affect bacteria resistant to other sulfonamides.
Indications: used for acute purulent-inflammatory lesions of the maxillofacial region, for the prevention of infectious complications after surgery.
Mode of application: appoint inside. Doses for adults are at the first dose of 1-2 g, depending on the severity of the disease, in the following days - 0.5-1 g. The interval between doses is 24 hours. The average duration of treatment is 5-7 days. The drug is used within 2-3 days after the temperature drops. For children under 13 years of age, the initial dose is 25 mg / kg of body weight, in the following days - 12.5 mg / kg.
Side effect: in isolated cases, dyspeptic symptoms, allergic reactions are possible.
Interaction with other drugs: when taken simultaneously with erythromycin, lincomycin, novobiocin, fusidine, tetracycline, antibacterial activity is mutually enhanced, the spectrum of action is expanded; with rifampicin, streptomycin, monomycin, kanamycin, gentamicin, nitroxylin - the antibacterial effect of the drug does not change; sometimes there is antagonism with nevigramon; with ristomycin, chloramphenicol, nitrofurans - a decrease in the total effect. In combination with antimalarial drugs, it has a pronounced effect on drug-resistant forms of malaria pathogens.
Release form: powder, tablets of 0.5 g.
Storage conditions: in a place protected from light.
Sulfathiazole(Sulfathiazole). Synonym: Norsulfazol (Norsulfasolum).
pharmachologic effect: has antibacterial properties against hemolytic streptococcus, pneumococcus, staphylococcus, gonococcus, Escherichia coli.
Indications: used for purulent-inflammatory diseases of the maxillofacial region, for the prevention and treatment of inflammatory diseases of periodontal tissues, the treatment of complicated forms of caries.
Mode of application: prescribed externally for applications on the mucous membrane and as part of gum dressings, pastes for the treatment of pulpitis and periodontitis. Inside taken in acute infectious and inflammatory diseases.
With staphylococcal infections, adults are prescribed 2 g for the first dose, in severe cases - up to 3-4 g, then 1 g every 6-8 hours. The duration of treatment is 3-6 days. For children, single doses are: from 4 months to 2 years - 0.1-0.25 g. 2-5 years - 0.3-0.4 g, 6-12 years - 0.4-0.5 g. At the first dose, give a double dose.
Side effect: possible nausea, vomiting, allergic reactions, leukopenia, neuritis, crystalluria.
Interaction with other drugs: when combined with PAS and barbiturates, the activity of the drug increases, with salicylates - activity and toxicity, with methotrexate and diphenine - toxicity, with phenacetin - hemolytic properties, with chloramphenicol - the possibility of developing agranulocytosis increases, with nitrofuran - the risk of anemia and methemoglobinemia, with anticoagulants indirect action increases the effect of the latter, with oxacillin - the activity of the antibiotic decreases. Incompatible with salts of iron and heavy metals. See also Sulfanilamide.
Contraindications: do not use with increased individual sensitivity to sulfonamides, diseases of the blood system, diffuse toxic goiter, kidney disease, acute hepatitis, intestinal obstruction.
Release form: powder, tablets of 0.25 and 0.5 g.
Storage conditions: list B.
Sulfacyl sodium(Sulfacilum-natrium). Synonyms: Albucid (Albucid-natricLim), Sulfacetamid.
pharmachologic effect: the drug is effective against streptococci, gonococci, pneumococci, Escherichia coli.
Indications: in dentistry, it is used topically for the treatment of infected wounds, infectious and inflammatory lesions of the oral mucosa and periodontal tissues.
Mode of application: used in the form of a powder - 5-6 times a day before epithelization, in the form of a solution - for washing periodontal pockets.
Side effect: rare. Possible local irritant effect at high concentrations.
Contraindications: do not prescribe if there is a history of allergic reactions to sulfa drugs.
Release form: powder; 30% solution in vials; ointment 30%.
Storage conditions: store the powder in a place protected from light. Solutions and ointment - in a cool, dark place. List B (except ointment).
The dentist's guide to medicines
Edited by Honored Scientist of the Russian Federation, Academician of the Russian Academy of Medical Sciences, Professor Yu. D. Ignatov
(sulfonamides) are broad-spectrum bacteriostatic drugs from the group of sulfanilic acid amide derivatives.
Given the bacteriostatic effect of sulfonamides, the therapeutic effect is not always observed, which is why they are often used. together with other chemotherapy drugs.
Who discovered sulfa drugs?
In 1935, G. Domag showed the chemotherapeutic properties of the first of them - prontosil- with streptococcal infections. The effect of this drug was also noted in pneumococcal, gonococcal and some other infections.
In the same year, prontosil was synthesized in the USSR under the name of red streptocide by O. Yu. Magidson and M. V. Rubtsov. It was soon established that the therapeutic effect of prontosil is exerted not by its entire molecule, but by the metabolite that splits off from it - sulfanilic acid amide(sulfanilamide), used independently and synthesized in the USSR under the name white streptocide, now known as streptocide and its sodium salt.
What are sulfonamides?
On the basis of this drug synthesized more than 10,000 sulfa drugs, of which about 40 have found application in medical practice as antibacterial agents, often differing significantly from the original drug in many ways.
The sulfonamides used in medical practice are white, odorless, finely crystalline powders, usually slightly soluble in water (their sodium salts are much more soluble).
Action (indications) of sulfanilic acid amide derivatives
Sulfonamides have antimicrobial action on the:
- many Gram-positive and Gram-negative bacteria
- some protozoa (plasmodia malaria, toxoplasma),
- chlamydia(in particular, pathogens of trachoma),
- actinomycetes of mycobacterium leprosy.
With the introduction of sulfanilamide at an underestimated dose or with an incomplete course of treatment, it may develop resistance to sulfanilamide-susceptible pathogens to its action, which has a cross character in relation to most of the drugs in this group. But resistance usually develops rather slowly. Determination of bacterial resistance to these drugs should be carried out only on special nutrient media without peptone, which weakens their action.
Distinguish a subgroup of sulfa drugs intended primarily for chemotherapy with intestinal infections, in particular in various forms of bacterial colitis, for example dysentery. These are ftalazol, sulgin and some others. Due to poor absorption in the intestines, sulfonamides create very high concentrations in them. Usually they are prescribed 1 g per reception, the first day 6 times, then gradually reducing the number of doses to 3-4, the course of treatment is usually 5-7 days.
Known sulfanilamide preparations for topical use. These are mainly drugs of the I group - short-acting.
Mechanism of antibacterial action of sulfonamides
The mechanism of the antibacterial action of sulfonamides is reduced to blocking sensitive microorganisms in the cells. folic acid synthesis, necessary for the subsequent formation of para-aminobenzoic acid, necessary for their development and reproduction. Therefore, derivatives of para-aminobenzoic acid, for example novocaine, anestezin, incompatible with sulfonamides, as well as methionomyxin and some other substances are incompatible with sulfonamides, as they weaken their action.
Classification of sulfa drugs
The choice of sulfonamides for the treatment of a patient is associated with the properties of the pathogen, as well as individual drugs, in particular, the rate of their release from the body, which is associated with the degree of lipophilicity of sulfonamides. Based on this, sulfa drugs are divided into several subgroups.
Short acting sulfonamides
These drugs have an elimination half-life in the body of less than 10 hours:
- streptocide;
- sulfadiazine;
- etazol;
- sulfazol;
- urosulfan;
- sulfacyl;
- some others, as well as their sodium salts.
Dosage
The dose for adults is usually about 1 g per dose 4-6 times a day. The course dose is up to 20-30 g. The course of treatment is up to 6-10 days.
In case of insufficient effectiveness of treatment sometimes 2-3 such courses are carried out, but in such cases it is better to use other chemotherapeutic drugs with a different spectrum and mechanism of action. The sodium salts of these sulfonamides, due to their greater solubility, are administered parenterally in the same doses.
Long acting sulfonamides
These drugs have a half-life of 24 to 48 hours:
- sulfanylpyridazine and its sodium salt;
- sulfadimethoxine;
- sulfamonomethoxin, etc.
Dosage
Assign adults to 0.5-1 g 1 time per day.
Ultra long acting sulfonamides
These drugs have a half-life greater than 48 hours, often 60-120 hours:
- sulfalene, etc.
Dosage
Assign according to two schemes: 1 time per day (the first day 0.8-1 g, the next 0.2 g) or 1 time per week at a dose of 2 g (more often in chronic diseases).
All drugs of these groups are rapidly absorbed in the intestines, which is why there is usually no need for their parenteral use, for which their sodium salts are prescribed. Sulfonamides are prescribed 30 minutes before a meal. Excreted mainly by the kidneys. For children, the dose is reduced accordingly.
Side effects of sulfa drugs
The most frequently observed side effects are dyspeptic and allergic.
Allergy
For allergic reactions prescribed antihistamines and calcium preparations especially gluconate and lactate. With minor allergic phenomena, sulfonamides are often not even canceled, which is necessary with more pronounced symptoms or more persistent complications.
Impact on the Central Nervous System
Possible phenomena from the central nervous system:
- headache;
- dizziness, etc.
Blood disorders
Sometimes there are changes in the blood:
- agranulocytosis;
- leukopenia, etc.
crystalluria
All side effects may be more persistent with the introduction of long-acting drugs that are more slowly excreted from the body. Because these poorly soluble drugs are excreted in the urine, they may form crystals in the urine. With an acid reaction of urine, it is possible crystalluria. To prevent this phenomenon, sulfa drugs should be taken with a significant amount of alkaline drink.
Sulfonamides contraindications
The main contraindications to the use of sulfa drugs are:
- increased individual sensitivity individuals to sulfonamides (usually to the whole group).
This may be indicated by anamnestic data on previous intolerance to other drugs of various groups.
Toxic effect on the blood with other drugs
Do not take sulfonamides together with other drugs that have toxic effect on the blood:
- griseofulvin;
- amphotericin preparations;
- arsenic compounds, etc.
Pregnancy and sulfonamides
Due to easy cross-placental barrier sulfonamides undesirable for pregnant women
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