Many synthetic substances from different classes of chemical compounds have antibacterial activity. The greatest practical value among them is:
- Sulfonamides.
- Quinolone derivatives.
- Nitrofuran derivatives.
- 8-hydroxyquinoline derivatives.
- Quinoxaline derivatives.
- Oxazolidinones.
Sulfonamide drugs include a group of compounds with a general structural formula:
General structure sulfonamides Para-aminobenzoic acid
Sulfonamides can be considered as derivatives of sulfanilic acid amide.
The chemotherapeutic activity of sulfonamide drugs was first discovered in 1935. German doctor and researcher G. Domagk, who published data on the successful clinical use of Prontosil (red
nal streptocide), synthesized as a dye. It was soon established that the “active principle” of red streptocide is sulfonamide (streptocide) formed during metabolism.
Subsequently, based on the sulfanilamide molecule, a large number of its derivatives were synthesized, some of which were widely used in medicine. The synthesis of various modifications of sulfonamides was carried out in the direction of creating more effective, long-acting and less toxic drugs.
In recent years, the use of sulfonamides in clinical practice has decreased, since their activity is significantly inferior to modern antibiotics and they have relatively high toxicity. In addition, due to many years of, often uncontrolled and unjustified use of sulfonamides, most microorganisms have developed resistance to them.
Sulfonamides have a bacteriostatic effect on microorganisms. The mechanism of the bacteriostatic effect of sulfonamides is that these substances, having a structural similarity to para-aminobenzoic acid (PABA), compete with it in the synthesis of folic acid, which is a growth factor for microorganisms.
Sulfonamides competitively inhibit dihydropteroate synthetase and also prevent the incorporation of para-aminobenzoic acid into dihydrofolic acid. Impaired synthesis of dihydrofolic acid reduces the formation of tetrahydrofolic acid from it, which is necessary for the synthesis of purine and pyrimidine bases (Fig. 37.1). As a result, synthesis is suppressed nucleic acids, which leads to inhibition of the growth and reproduction of microorganisms.
Sulfonamides do not disrupt the synthesis of dihydrofolic acid in the cells of the macroorganism, since the latter do not synthesize, but utilize the finished dihydrofolic acid.
In environments where there is a lot of PABA (pus, tissue decay), sulfonamides are ineffective. For the same reason, they have little effect in the presence of procaine (novocaine) and benzocaine (anesthesin), which hydrolyze to form PABA.
Long-term use of sulfonamides leads to the emergence of resistance on the part of microorganisms.
Initially, sulfonamides were active against wide range gram-positive and gram-negative bacteria, but currently
Para-aminobenzoic acid ^ Dihydropteroate synthetase - *-» | lt; Sulfonamides D and hydrofolic acid Dihydrofolate reductase + > | lt; -- Trimethoprim Tetrahydrofolic acid
Synthesis of purines and thymidine
DNA and RNA synthesis
Growth and reproduction of microorganisms Fig. 37.1. Mechanism of action of sulfonamides and trimethoprim.
many strains of staphylococci, streptococci, pneumococci, gonococci, and meningococci have become resistant. Sulfonamides retained their activity against nocardia, toxoplasma, chlamydia, malarial plasmodia and actinomycetes.
The main indications for prescribing sulfonamides are: nocardiosis, toxoplasmosis, tropical malaria resistant to chloroquine. In some cases, sulfonamides are used for coccal infections, bacillary dysentery, and infections caused by Escherichia coli.
Sulfonamides practically do not differ from each other in their spectrum of activity. The main difference between sulfonamides lies in their pharmacokinetic properties.
- Sulfonamides for resorptive action (well absorbed from the gastrointestinal tract) intestinal tract)
- Short-acting (t1/2lt;10 h)
- Average duration of action (t1/210-24 h)
- Long-acting (tJ/2 24-48 h)
- Extra long-acting (t]/2gt;48 h)
- Sulfonamides acting in the intestinal lumen (poorly absorbed from the gastrointestinal tract)
- Sulfonamides for topical use
- Combined preparations of sulfonamides and salicylic acid
- Combination preparations of sulfonamides with trimethoprim
Drugs for resorptive action are well absorbed from the gastrointestinal tract. The highest concentrations in the blood are created by drugs with short and medium duration of action. Long- and extra-long-acting drugs bind to blood plasma proteins to a greater extent. They are distributed throughout all tissues, pass through the blood-brain barrier, the placenta, and accumulate in the serous cavities of the body. The main pathway for the conversion of sulfonamides in the body is acetylation, which occurs in the liver. Degree of acetylation for different drugs not the same. Acetylated metabolites are pharmacologically inactive. The solubility of acetylated metabolites is significantly worse than that of the parent sulfonamides, especially at acidic urine pH, which can lead to the formation of crystals in the urine (crystalluria). Sulfonamides and their metabolites are excreted primarily by the kidneys.
Sulfanilamide is one of the first antimicrobial drugs with a sulfanilamide structure. Currently, the drug is practically not used due to low efficiency and high toxicity.
Sulfathiazole, sulphaethidol, sulfadimidine and sulphacarbamide are used 4-6 times a day. Urosulfan is used to treat
infections urinary tract, since the drug is excreted unchanged by the kidneys and creates high concentrations in the urine. Sulfamethoxazole is part of the combination drug “Co-trimoxazole”. Sulfa - monomethoxine and Sulfadimethoxine are prescribed 1-2 times a day.
Sulfamethoxypyrazine is used daily for acute or rapidly occurring infectious processes, 1 time every 7-10 days - for chronic, long-term infections.
Sulfonamides for resorptive action cause a lot side effects. When used, blood system disorders (anemia, leukopenia, thrombocytopenia), hepatotoxicity, allergic reactions (skin rashes, fever, agranulocytosis), and dyspeptic disorders are possible. With acidic urine pH values, crystalluria occurs. To prevent the occurrence of crystalluria, sulfonamides should be washed down with alkaline mineral water or soda solution.
Sulfonamides acting in the intestinal lumen are practically not absorbed in the gastrointestinal tract and create high concentrations in the intestinal lumen, therefore they are used in the treatment of intestinal infections (bacillary dysentery, enterocolitis), as well as for the prevention of intestinal infections in postoperative period. However, at present, many strains of intestinal pathogens have acquired resistance to sulfonamides. To increase the effectiveness of treatment, simultaneously with sulfonamides acting in the intestinal lumen, it is advisable to prescribe well-absorbed drugs (Etazol, Sulfadimezin, etc.), since the causative agents of intestinal infections are localized not only in the lumen, but also in the intestinal wall. When taking drugs of this group, B vitamins should be prescribed, since sulfonamides inhibit the growth of Escherichia coli, which is involved in the synthesis of B vitamins.
Phthalylsulfathiazole has an antimicrobial effect after the cleavage of phthalic acid and the release of the amino group. Active beginning phthalylsulfathiazole is norsulfazole.
Phthalylsulfathiazole is prescribed 4-6 times a day. The drug is low toxic. It causes virtually no side effects.
Sulfaguanidine is similar in action to phthalylsulfathiazole.
Sulfacetamide is a sulfonamide for topical use, which is used in ophthalmic practice in the form of solutions (10-20-30%) and ointments (10-20-30%) for conjunctivitis, blepharitis, purulent corneal ulcers and gonorrheal eye diseases. The drug is usually well tolerated. Sometimes, especially when using more concentrated solutions, it is observed irritant effect; in these cases, solutions of lower concentrations are prescribed.
Silver sulfadiazine and silver sulfathiazole are distinguished by the presence of a silver atom in the molecule, which enhances their antibacterial effect. The drugs are used topically in the form of ointments for burn and wound infections.
tions, trophic ulcers, bedsores. When using drugs, allergic skin reactions may develop.
Combination drugs that combine fragments of sulfanilamide and salicylic acid in their structure include salazosulfapyridine, salazopyridazine, salazodimethoxin. In the large intestine, under the influence of microflora, hydrolysis of these compounds occurs to 5-aminosalicylic acid and the sulfanilamide component. All these drugs have antibacterial and anti-inflammatory effects. Used for nonspecific ulcerative colitis and Crohn's disease, and also as basic agents in the treatment of rheumatoid arthritis. 
Salazosulfapyridine (sulfasalazine) is an azo compound of sulfapyridine with salicylic acid. The drug is prescribed orally. When taking the drug, allergic reactions, dyspeptic symptoms, burning in the rectum, and leukopenia may occur.
Salazopyridazine and salazodimethoxine have similar properties. 
Trimethoprim is a pyrimidine derivative that has a bacteriostatic effect. The drug blocks the reduction of dihydrofolic acid to tetrahydrofolic acid due to inhibition of dihydrofolate reductase.
The affinity of trimethoprim for bacterial dihydrofolate reductase is 50,000 times higher than for mammalian cell dihydrofolate reductase.
The combination of trimethoprim with sulfonamides is characterized by a bactericidal effect and a wide spectrum of antibacterial action, including microflora resistant to many antibiotics and conventional sulfonamides.
The most well-known drug from this group is Co-trimoxazole, which is a combination of 5 parts of sulfamethoxazole (sulfonamide of medium duration of action) and 1 part of trimethoprim. The choice of sulfamethoxazole as a component of Co-trimoxazole is due to the fact that it has the same elimination rate as trimethoprim.
Co-trimoxazole is well absorbed from the gastrointestinal tract, penetrates many organs and tissues, creates high concentrations in bronchial secretions, bile, urine, prostate gland. Penetrates through the BBB, especially during inflammation of the meninges. It is excreted mainly in the urine.
The drug is used for respiratory and urinary tract infections, surgical and wound infections, and brucellosis.
When using the drug, side effects occur that are characteristic of resorptive sulfonamides. Co-trimoxazole is contraindicated in cases of severe dysfunction of the liver, kidneys and hematopoiesis. The drug should not be prescribed during pregnancy.
Similar drugs are: lidaprim (sulfametrol + trimethoprim), sulfatone (sulfamonomethoxine + trimethoprim), poteseptil (sulfadimezin + trimethoprim).
QUINOLONE DERIVATIVES
Quinolone derivatives are represented by non-fluorinated and fluorinated compounds. Compounds containing an unsubstituted or substituted piperazine ring at position 7 of the quinolone ring and a fluorine atom at position 6 have the greatest antibacterial activity. These compounds are called fluoroquinolones.
General structural formula fluoroquinolones
Classification of quinolone derivatives
- Non-fluorinated quinolones
- Fluoroquinolones (first generation drugs)
- Fluoroquinolones (new drugs of the second generation)
The founder of the group of non-fluorinated quinolones is nalidixic acid. The drug is active only against certain gram-negative microorganisms - Escherichia coli, Shigella, Klebsiella, Salmonella. Pseudomonas aeruginosa is resistant to nalidixic acid. Resistance of microorganisms to the drug occurs quickly.
The drug is well absorbed from the gastrointestinal tract, especially on an empty stomach. High concentrations of the drug are created only in the urine (about 80% of the drug is excreted unchanged in the urine). t]/2 1-1.5 hours.
Nalidixic acid is used for urinary tract infections (cystitis, pyelitis, pyelonephritis). The drug is also prescribed for the prevention of infections during kidney and bladder surgeries.
When using the drug, dyspeptic disorders, central nervous system stimulation, liver dysfunction, and allergic reactions are possible.
Nalidixic acid is contraindicated in renal failure.
Oxolinic acid and pipemidic acid are similar in pharmacological action to nalidixic acid.
Fluoroquinolones have the following general properties:
- Drugs of this group inhibit the vital enzyme of the microbial cell - DNA gyrase (type II topoisomerase), which ensures supercoiling and covalent closure of DNA molecules. Blockade of DNA gyrase leads to uncoupling of DNA strands and, accordingly, to cell death (bactericidal effect). The selectivity of the antimicrobial action of fluoroquinolones is due to the fact that type II topoisomerase is absent in the cells of the macroorganism.
- Fluoroquinolones are characterized by a wide spectrum of antibacterial action. They are active against gram-positive and gram-negative cocci, Escherichia coli, Salmonella, Shigella, Proteus, Klebsiella, Helicobacter, Pseudomonas aeruginosa. Certain drugs (ciprofloxacin, ofloxacin, lomefloxacin) act against mycobacterium tuberculosis. Spirochetes, Listeria and most anaerobes are not sensitive to fluoroquinolones.
- Fluoroquinolones act on extracellular and intracellular microorganisms.
- Drugs in this group are characterized by a pronounced post-antibiotic effect.
- Microflora resistance to fluoroquinolones develops relatively slowly.
- Fluoroquinolones create high concentrations in the blood and tissues when taken orally, and bioavailability is independent of food intake.
- Fluoroquinolones penetrate well into various organs and tissues: lungs, kidneys, bones, prostate, etc.
When using fluoroquinolones, allergic reactions, dyspeptic symptoms, and insomnia are possible. Drugs in this group inhibit the development of cartilage tissue, so they are contraindicated for pregnant and nursing mothers; in children can be used only for health reasons. In rare cases, fluoroquinolones can cause the development of tendinitis (inflammation of the tendons), which may cause physical activity may lead to their ruptures.
New fluoroquinolones (II generation) exhibit higher activity against gram-positive bacteria, primarily pneumococci: the activity of levofloxacin and sparfloxacin exceeds the activity of ciprofloxacin and ofloxacin by 2-4 times, and the activity of moxifloxacin by 4 or more times. It is important that the activity of the new fluoroquinolones does not differ between penicillin-sensitive and penicillin-resistant strains of pneumococcus.
New fluoroquinolones have more pronounced activity against staphylococci, and some drugs retain moderate activity against methicillin-resistant staphylococci.
If first generation drugs have moderate activity in relation to chlamydia and mycoplasmas, the second generation drugs are high, comparable to the activity of macrolides and doxycycline.
Some new fluoroquinolones (moxifloxacin, etc.) have good activity against anaerobes, including Clostridium spp. and Bacteroides spp., which allows them to be used for mixed infections as monotherapy.
The main use of new fluoroquinolones is community-acquired respiratory tract infections. The effectiveness of these drugs has also been shown for infections of the skin and soft tissues, and urogenital infections.
The most well studied of the new fluoroquinolones is levofloxacin, which is a levorotatory isomer of ofloxacin. Since levofloxacin exists in two dosage forms - parenteral and oral, it is possible
its use for severe infections in the hospital. The bioavailability of the drug is close to 100%. Clinical effectiveness Levofloxacin with a single dose of 250-500 mg/day is a significant advantage of the drug, however, for generalized infectious processes that occur in severe form, levofloxacin is prescribed twice a day.
The formation of resistance to levofloxacin is possible, but resistance to it develops slowly and does not cross with other antibiotics.
Levofloxacin has proven to be the safest fluoroquinolone with low level hepatotoxicity. It is the safest, along with ofloxacin and moxifloxacin, with regard to its effect on the central nervous system. Side effects on cardiovascular system are much less common than with other fluoroquinolones. Increasing the dose of levofloxacin to 1000 mg/day does not lead to an increase in side effects, and their likelihood does not depend on the age of the patient.
In general, the level of side effects associated with the use of levofloxacin is the lowest among fluoroquinolones, and its tolerability is considered to be very good.
NITROFURAN DERIVATIVES
Nitrofuran derivatives with antimicrobial activity are characterized by the presence of a nitro group at the C5 position and various substituents at the C2 position of the furan ring:
General structural formula of nitrofurans
Nitrofurans
Nitrofurazone (Furacilin), nitrofurantoin (Furadonin), furazolidone, furazidin (Furagin).
The general properties of nitrofuran derivatives include the following:
- ability to disrupt DNA structure. Depending on the concentration, nitrofurans have a bactericidal or bacteriostatic effect;
- a wide spectrum of antimicrobial action, which includes bacteria (Gram-positive cocci and gram-negative bacilli), viruses, protozoa (Giardia, Trichomonas). Nitrofuran derivatives are capable of acting on strains of microorganisms that are resistant to certain antibiotics. Nitrofurans have no effect on anaerobes and Pseudomonas aeruginosa. Resistance to nitrofurans is rare;
- high frequency of adverse reactions that occur when taking drugs.
(for external use) for the treatment and prevention of purulent-inflammatory processes.
Nitrofurantoin creates high concentrations in urine, therefore it is used for urinary tract infections.
Furazolidone is poorly absorbed from the gastrointestinal tract and creates high concentrations in the intestinal lumen. Furazolidone is used for intestinal infections bacterial and protozoal etiology.
Furazidine is used orally for urinary tract infections and topically for rinsing and douching in surgical practice.
Nitrofuran derivatives can cause dyspeptic disorders, so nitrofurans should be taken during or after meals. Drugs in this group are characterized by hepatotoxic, hematotoxic and neurotoxic effects. With prolonged use, nitrofuran derivatives can cause pulmonary reactions (pulmonary edema, bronchospasm, pneumonitis).
Nitrofuran derivatives are contraindicated in cases of severe renal and liver failure and pregnancy.
8-OHYQUINOLINE DERIVATIVES
Antimicrobial agents in this group include 5-nitro-8-hydroxyquinoline-nitroxoline (5-NOK). Nitroxoline has a bacteriostatic effect due to the selective inhibition of bacterial DNA synthesis. The drug has a wide spectrum of antibacterial action. It is well absorbed from the gastrointestinal tract and is excreted unchanged by the kidneys, which is why there is a high concentration of the drug in the urine.
Nitroxoline
Nitroxoline is used to treat urinary tract infections and to prevent infections after surgery on the kidneys and urinary tract. The drug is usually well tolerated. Sometimes dyspeptic symptoms are observed. When treated with the drug, urine turns saffron-yellow.
QUINOXALINE DERIVATIVES
Some quinoxaline derivatives have pronounced antibacterial activity. Drugs in this group include quinoxidine and dioxidine. Quinoxaline derivatives have a bactericidal effect, which is associated with the ability to activate peroxidation processes, leading to disruption of DNA biosynthesis and deep structural changes in the cytoplasm of a microbial cell. Due to their high toxicity, quinoxaline derivatives are used only for life-saving indications for the treatment of severe forms of anaerobic or mixed aerobic-anaerobic infection caused by multidrug-resistant strains when other antimicrobial agents are ineffective. Quinoxidine and dioxidine are prescribed only to adults in a hospital setting. The drugs are highly toxic; cause dizziness, chills, convulsive muscle contractions, etc.
OXAZOLIDINONES
Oxazolidinones are a new class of synthetic antibacterial agents, highly active against gram-positive microorganisms.
Linezolid is the first drug of this class, registered in the Russian Federation under the patented (trade) name Zyvox. It is characterized by the following properties:
- the ability to inhibit protein synthesis in a bacterial cell. Unlike other antibiotics that act on protein synthesis, linezolid acts at the early stages of translation by irreversibly binding to the 30S and SOS subunit of ribosomes, as a result of which the formation of the 708 complex and the formation of the peptide chain are disrupted. This unique mechanism of action prevents the development of cross-resistance with antibiotics such as macrolides, aminoglycosides, lincosamides, tetracyclines, chloramphenicol;
- type of action - bacteriostatic. Bactericidal activity has been noted for Bacteroides fragilis, Clostridium perfringens and some strains of streptococci, including Streptococcus pneumoniae and Streptococcus pyogenes;
- the spectrum of action includes the main gram-positive microorganisms, including methicillin-resistant staphylococci, penicillin- and macrolide-resistant pneumococci and glycopeptide-resistant enterococci. Linezolid is less active against gram-negative bacteria;
- V high degree accumulates in the bronchopulmonary epithelium. Penetrates well into the skin, soft tissues, lungs, heart, intestines, liver, kidneys, central nervous system, synovial fluid, bones, gall bladder. Has 100% bioavailability;
- resistance develops very slowly. The development of resistance to linezolid is associated with long-term parenteral use (4-6 weeks).
The following dosage regimen is recommended: 600 mg (orally or intravenously) every 12 hours. Linezolid can be used as follows: step therapy with initial administration parenterally, then orally (on days 3-5), which determines its pharmacoeconomic advantages as an alternative to vancomycin. For the treatment of skin and soft tissue infections, the dose is 400 mg every 12 hours.
Linezolid was well tolerated both orally and intravenous use. The most commonly reported side effects were gastrointestinal (diarrhea, nausea, tongue staining), headache and skin rash. Usually these phenomena are not severe in intensity and do not last long. When using linezolid for more than 2 weeks, reversible thrombocytopenia is possible.
Linezolid is a monoamine oxidase inhibitor and may therefore enhance the effects of dopamine, adrenaline and serotonin. When taken together, it is possible to increase the pressor response to dopaminergic, vasopressor or sympathomimetic drugs, which requires a dose reduction. Linezolid oral suspension contains phenylaline and should be avoided in patients with phenylketonuria.
Interaction of synthetic antibacterial drugs with other drugs
End of the table
|
1 |
2 |
3 |
|
|
NSAIDs |
Increased concentration of sulfonamides in blood plasma |
|
Levomycetin |
Strengthening the hematotoxic effect of chloramphenicol and sulfonamides |
|
|
Fluoroquinolones |
Antacids, iron supplements |
Reduced bioavailability of fluoroquinolones |
|
NSAIDs |
Increased neurotoxic effect of fluoroquinolones |
|
|
Indirect anticoagulants |
Increased risk of bleeding |
|
|
Nitrofurans (furazolidone) |
Levomycetin |
Increased hematotoxic effect of interacting drugs |
|
Alcohol |
Disulfiram-like reaction |
|
|
MAO inhibitors |
Hypertensive crisis |
Basic drugs
|
International nonproprietary name |
Patented (trading) titles |
Release forms |
Patient Information |
|
1 |
2 |
3 |
4 |
|
Sulfathiazole (Sulfathiazolum) |
Norsulfazole |
|
The drugs are taken on an empty stomach 30-40 minutes before meals. It is necessary to take the medications with plenty of alkaline drinks. During treatment it is necessary to carry out blood and urine tests |
|
Sulfaethidol (Sulfaethidolum) |
Etazol |
Powder, tablets 0.25 and 0.5 g |
|
|
Sulfacarbamidum |
Urosulfan |
Powder, tablets 0.5 g |
|
|
Sulfadimethoxin (Sulfa- dimethoxinum) |
Madribon |
Powder, tablets 0.2 and 0.5 g |
|
|
Sulfameth- sipyrazine (Sulfametho- xypyrazine) |
Sulfalene |
Powder, tablets 0.25 and 0.5 g |
|
|
Trimethoprim + Sulfa-methoxazolum |
Co-trimox - 30 l, Bactrim, Biseptol |
Tablets (1 tablet contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim) |
|
End of the table
|
1 |
2 |
3 |
4 |
|
Salazosulfa- pyridine (Salazosulfapy- ridinum) |
Sulfasalazine |
Tablets 0.5 g |
Take 0.5 g orally 4 times a day 30-40 minutes before meals with a full glass of water. |
|
Ciprofloxacin (Ciprofloxacinum) |
Tsiprobay, Tsifran, Tsiprolet |
Tablets of 0.25, 0.5 and 0.75 g; 0.2% solution for infusion in bottles of 50 and 100 ml |
When taken orally, drink with a full glass of water. If you miss a dose, take it as soon as possible; do not take double doses. Avoid direct exposure to sunlight and ultraviolet rays |
|
Ofloxacin (Ofloxacinum) |
Tariwid |
Tablets 0.2 g |
|
|
Lomefloxacin (Lomefloxacin) |
Maxaquin |
Tablets 0.4 g |
|
|
Nitrofurantoinum |
Furadonin |
Tablets of 0.05 and 0.1 g |
Take orally after meals with a drink sufficient quantity water (100-200 ml). Do not take double doses. During treatment with furazolidone you should not use alcoholic drinks |
|
Furazolidone (Furazolidonum) |
|
Tablets 0.05 g |
|
|
Nitroxoline (Nitroxolinum) |
5-NOK |
Tablets 0.05 g |
Take 1 hour before meals |
Sulfonamides
Drugs in this group are prescribed for intolerance to antibiotics or microflora resistance to them. In terms of activity, they are significantly inferior to antibiotics and in recent years their importance for the clinic has been decreasing. Sulfonamides are close in structure to para-amnobenzoic acid. The mechanism of action of the drugs is associated with their competitive antagonism with paraaminobenzonic acid, which is used by microorganisms for the synthesis of dihydrofolic acid. Violation of the synthesis of the latter leads to blockade of the formation of purine and pyrinmidine bases and suppression of the proliferation of microorganisms (bacteriostatic effect).
Sulfonamides are active against gram-positive and gram-negative cocci, Escherichia coli, Shigella, Vibrio cholerae, Clostrindia, protozoa (malarial plasmodium and toxoplasma), chlamydia; causative agents of anthrax, diphtheria, plague, as well as Klebsiella, Actinnomnceta and some other microorganisms.
Depending on absorption from the gastrointestinal tract and the duration of elimination from the body, the following groups of sulfonamides are distinguished:
A. Sulfonamides with good absorption:
short-term action (T1/2 - 8 hours); norsulfazole, sulfadimezin, urosulfan, etazol, sodium sulfacyl;
medium duration of action (T1/2 - 8-20 hours): sulfazine and other drugs (these drugs are not widely used);
long-acting (T1/2 - 24-48 hours): sulfapridaznn,
sulfadimethoxine (sulfomethoxazole), sulfamonomethoxine and other drugs;
extra-long action (T1/2 - 65 hours); sulfalene
B. Sulfonamides, poorly absorbed from the gastrointestinal tract and slowly released from the body: sulgin, phthalazole, ftaznn, salazopyridazine and other drugs. ^^ ^
The duration of action of sulfonamides depends on the formation of labile bonds with albumin. From the blood, sulfonamides penetrate quite well into various tissues and body fluids. Sulfapyrndase has the greatest penetrating ability. Sulfadimethoxine accumulates in significant quantities in bile. All sulfonamides penetrate the placenta well. Sulfonamides are metabolized (acetylated) in the liver. At the same time, their activity is lost and toxicity increases; in some of them, solubility in a neutral and especially in an acidic environment sharply decreases, which can contribute to their precipitation in the urinary tract (crystalluria). The degree and rate of acetyllation of various sulfonamides is not the same. Those drugs that are acetylated to a small extent are excreted from the body in an active form, and this determines their greater antimicrobial activity in the urinary tract (etazol, urosulfan). Sulfanilamides can be synthesized in the body through the formation of inactive glucuronides. This inactivation pathway is particularly characteristic of sulfadimethoxine. Sulfonamide glucuronides are highly soluble in water and do not precipitate in the kidneys. Sulfonamides and their metabolites are excreted by the kidneys.
The sensitivity of microbes to sulfonamides decreases sharply in environments where there is a high concentration of para-aminobenzoic acid, for example, in a purulent focus. The activity of long-acting drugs decreases in the presence of folic acid, methionine, purine and pnrimidine bases. The competitive mechanism of action of these drugs requires the creation of a high concentration of sulfonamides in the patient’s blood for successful treatment infections. To do this, the first loading dose should be prescribed, 2-3 times higher than the average therapeutic dose, and maintenance doses should be prescribed at certain intervals (depending on the half-life of the drug).
Side effects during treatment with sulfonamides are common to the entire group: effects on the blood and central nervous system; dysbiosis. Taking drugs can cause methhemoglobnemia and hyperglobinemia, especially in newborns. Therefore, it is not recommended to prescribe these drugs, especially long-acting ones, to pregnant women shortly before childbirth or to newborns.
Biseptol (sulfatene, co-trnoxazole) is a combination of sulfonamide - sulfamethoxazole with the drug trimethoprim. Trnmethoprim inhibits the activity of an enzyme important for the synthesis of folic acids - dagndrofolagreductase. This combined drug has a bactericidal effect. In patients, it can cause hematopoietic disorders (leukopenia, agranulocytosis),
Salase compounds of sulfonamides
Salazosulfapirishchi (sulfasalazine) is a nitrogen combination of sulfetyryadin (sulfadine) with salicylic acid. High activity of this drug is noted against diplococcus, streptococcus, gonococcus, Escherichia coli. The determining role in the mechanism of action is played by the ability of the drug to accumulate in connective tissue (including the intestines) and gradually break down into 5-ash salicylic acid (which is excreted in feces) and eulfyalides, which have an anti-inflammatory and antibacterial effect in the intestines. The medicine is used for non-specific ulcerative colitis. Salazopyrndase and salshodimethoxine have a similar mechanism of action and indications.
4- and 8-hydroxyquinoline derivatives
The drugs in this group are halogen- and nitro-derivatives of oxnquinolnia. They act mainly on the gram-negative flora, and also have an anti-rotozoal effect (dysenteric amoeba, Giardia, trichomonas, balantidia). Based on their pharmacokinetic properties, hydroxyquinol derivatives are divided into two groups; poorly absorbed (enteroseptol, mexaform, mekeaza "intestopaya) and well absorbed from the gastrointestinal tract (nntrosolnn),
Enteroseptol is active against Escherichia coli, putrefactive bacteria, pathogens of amoebic and bacillary dysentery. It is practically not absorbed from the gastrointestinal tract, therefore its high concentration is created in the intestinal lumen, which is also used in surgical practice for sterilization of the intestine before operations on this organ. Enteroseptol is machotoxic, but when taking it, dyspeptic phenomena are possible, more often by 2 1st or 3rd day of use Enteroseptol contains iodine, so symptoms of iodine are possible: runny nose, cough, joint pain, skin rashes, anti-inflammatory drug! in case of hyperthyroidism, Enteroseptol is included in the complex of complex prepphaggs; dermozolon, mexaform, mexate
Due to side effects (dysneptic disorders, neuritis, myelopathy, damage optic nerve) oxygen derivatives began to be used less frequently.
Nntrosolnn (5-NOK). a drug that is considered the least toxic compared to other oxoquinolines. It has a wide spectrum of action against gram-positive (S, aureus, S. pyogenes, Enterococcus, Diplococcus, Corinebaeterium) and gram-negative (P. vulg^is, Salmonella, Shigella, P. aeruginosa) pathogens, as well as fungi (C. albicans). Nnthroxoline is absorbed well. The drug penetrates well into the prostate tissue. Almost the entire amount of the drug is excreted unchanged by the kidneys, which, taking into account the spectrum of action (ashroxolin acts on all pathogens of infection of the urogenital tract), allows it to be used exclusively as a uroseptic.
Quinolones
Quinolones are a large group of amino acids, united by a single mechanism of action: inhibition of the enzyme of the bacterial cell - DNA gyrases. First Syntchem 3
A drug from the quinolone class was nalidixic acid (negram), used since 1962. This drug, due to its pharmacokinetics (excreted by the kidneys in an active form) and spectrum of antimicrobial action, is indicated for the treatment of urinary tract infections and some intestinal infections (bacterial enterocolitis, dysentery)
Antibacterial preparations of the fluoroquinol group
Drugs belonging to this group were obtained by introducing a fluorine atom into the 6th position of the quinolone molecule. Depending on the number of fluorine atoms, monofluorinated (profloxacin, ofloxacin, pefloxacin, norfloxacin), dnfluorinated (lomefloxacin) and trifluorinated (fleroxacin) compounds are distinguished.
The first drugs of the fluoroquinolone group were proposed for clinical practice in 1978 -1980. The intensive development of the group of fluoroquinlonones is due to a wide spectrum of action, high antimicrobial activity, bactericidal effect, optimal pharmacological properties, and good tolerability with long-term use.
Fluoroquinlonones are drugs with a broad antimicrobial spectrum, covering gram-negative and gram-positive aerobic and anaerobic microorganisms.
Fluoroquinolones have high activity against most gram-negative bacteria (Neisseria spp., Haemophius spp., E. coli, Shigella spp., Salmonella spp.).
Sensitive microorganisms include Klebsiella spp., Proteus spp., Enterobacter spp., Legionella spp., Yersinia spp., Campylobacter spp., Staphylococcus spp. (including strains resistant to eticillin), some strains of Clostridiuni (C. perfringens). Among Psedomonas strains, including P. aerugmosa, as well as Streptococcus spp. (including S. pneumonias) there are both sensitive and moderately sensitive strains
As a rule, Brocella spp., Corynebacterim spp., Chlamydiaspp, Mycobacterium tuberculosis, and anaerobic streptococci are moderately sensitive.
Fungi, viruses, treponemes and most protozoa are resistant to fluoroquinolones.
The activity of fluoroquinolones against gran-positive microbes is less pronounced than against gram-negative ones. Streptococci are less sensitive to fluoroquinolones than staphylococci.
Among fluoroquinlonones, ciprofloxacin exhibits the highest in vitro activity against gram-negative microorganisms, and ciprofloxacin and ofloxacin show the highest activity against gram-positive microorganisms.
The mechanism of action of fluoroquinolones is associated with the effect on DNA gyrase. This enzyme is involved in the processes of replication, genetic recombination and DNA repair. DNA gnase causes negative superspinning, converting DNA into a covalently closed circular structure, and also leads to reversible binding of DNA turns. The binding of fluoroquinolones to DNA gene leads to the death of bacteria.
Pharmacokinetics, Fgorquinolones are rapidly absorbed in the gastrointestinal tract, reaching maximum concentrations in the blood after 1-3 hours. Eating slightly slows down the absorption of drugs without affecting the amount of absorption. Fluoroquinlonones are characterized by high bioavailability when taken orally, which for most drugs reaches 80-100% (the exception is norfloxacin, the bioavailability of which after oral administration is 35-45%). The duration of circulation of fluoroquinolones in the human body (for most drugs the T1/2 indicator is 5-10 hours) allows them to be prescribed 2 times a day. Fluoroquinolones are bound to a low degree by serum proteins (in most cases less than 30%). The drugs have a large volume of distribution (90 liters or more), which indicates their good penetration into various tissues, where concentrations are created, in many cases close to or exceeding low concentrations. Fluoroquinolones penetrate well into the mucous membranes of the gastrointestinal tract, genitourinary and respiratory tracts, lungs, kidneys, synovial fluid, where concentrations are more than 150% relative to serum levels; the penetration rate of fluoroquinolone into sputum, skin, muscles, uterus, inflammatory fluid and saliva is 50-150%, and into the cerebrospinal fluid, fat and eye tissue - less than 50%. Good diffusion of fluoroquinlonones in tissue is due to high lipid density and low protein binding,
Fluoroquinolones metabolize in the body, with pefloxacin being the most susceptible to biotransformation (50 - 85%), and ofloxacin and lomefloxanine being the least susceptible (less than 10%); Other drugs occupy an intermediate position in terms of the degree of metabolism. The number of metabolites formed ranges from 1 to 6. A number of metabolites (ozhso-, dezmetnl-v formnl-) have some antibacterial activity.
Elimination of fluoroquinolones in the body is carried out by renal and extrarenal (notransformation in the liver, excretion in bile, excretion in feces, etc.) ways. When fluoroquinolones (ofloxacin and lomefloxacin) are excreted by the kidneys, concentrations are created in the urine that are sufficient to suppress microflora sensitive to NNM for a long time,
Clinical application. Fluoroquinlonones are widely used in patients with urinary tract infections. Efficiency in severe and complicated infections is 70-100%, Good results have been obtained in patients with bacterial and bacterial chlamydial prostatitis (55-100%),
Fluoroquinolones are effective against sexually transmitted infections, primarily gonorrhea. For acute uncomplicated gonorrhea of different localization (including the pharynx and rectum), the effectiveness of fluoroquinlonones is 97. 100% even with one-time use. A less pronounced effect of fluoroquinlonones is observed in urogenital infections caused by chlamydia (elimination of the pathogen is 45-100%) and mucoplasma (33-100%). For syphilis, drugs of this group are not used,
Good results with the use of fluoroquinolones are observed in intestinal infections (salmonellosis, dysentery, various shapes bacterial diarrhea).
In cases of respiratory diseases, fluoroquinolones have important in the treatment of lower respiratory tract infections (pneumonia, bronchitis, bronchostatic disease) caused by gram-negative microflora, including P. awuginosa.
The use of fluoroquinolones as first-line drugs for upper respiratory tract infections is inappropriate.
Fluoroquinolones are effective drugs for the treatment of severe forms of purulent-inflammatory processes in the skin, soft tissues, purulent arthritis, chronic osteomyelitis caused by gram-negative aerobic bacteria (including P, aemgi-poaa) and S. al-esh.
Considering the good penetration of fluoroquinlonones into gynecological tissues (uterus, vagina, the fallopian tubes, ovaries^ they are successfully used in the treatment of acute inflammatory diseases of the pelvic organs,
Fluoroquinlonones (parenterally or orally) are effective in septic processes accompanied by bacteremia caused by gramstricagel and gram-positive aerobic microorganisms
Fluoroquinlonones (ciprofloxacin, ofloxacin, nefgoxacin) are successfully used in the treatment of secondary bacterial meningitis.
Adverse reactions. Adverse reactions when using fluoroquinlonones occur mainly from the gastrointestinal tract (up to 10%) (nausea, vomiting, anorexia, gastric discomfort) and the central nervous system (0.5.6%) (headache, dizziness, frustration sleep or mood, agitation, tremor, depression), Allergic reactions caused by fluorochloramines occur in no more than 2% of patients, Skin reactions are noted in 2% > in addition, photosensitivity is observed. Fluorochloramines slow down the growth of cartilage tissue in young animals ; it is not known whether they affect bone tissue in children. However, these drugs are not recommended for use in children under 12 years of age and pregnant women.
Ciprofloxacin (shshrobay, tsnfloksnnal) is one from the most active and widely used drugs of this group. It penetrates well into various organs and tissues, cells. Up to 100% of the drug is absorbed into sputum, 90-80% into pleural fluid, and up to 200-1000% of the drug into lung tissue. The drug is used for respiratory tract infections, urinary tract, osteomyelitis, abdominal infection, skin and appendage lesions
Pefloxacin (peflacin, abakgal) is a fluoroquinolone that exhibits high activity against Enterobacteriaceae and gram-negative cocci. Gram-positive staphylococci and streptococci are less sensitive to pefloxacin than gram-positive bacteria. Pefloxacin exhibits high activity against intracellularly located bacteria (hempnids, legionella, mycoplasmas). It is well absorbed when taken orally, in high concentrations it is determined in organs and tissues, including bones, accumulates well in the skin, muscles, fascia, pernoneal fluid, in the abdominal organs, prostate, and penetrates the BBB.
Pefloxacin is actively metabolized in the liver with the appearance of active compounds: N-demethylpefloxacin (norfloxacin), N-oxidepefloxacin, oxodemetshefloxa-cin and others. The drug is eliminated by the kidneys and is partially excreted in the bile.
Ofloxacin (floxnn, tarivid) belongs to the monofluorinated hnnolones. Its antimicrobial activity is close to that of ciprofloxacin, but there is higher activity against Staphylococcus aureus. At the same time, ofloxacin has better pharmacological parameters, better bioavailability, a longer half-life and higher concentrations in serum and tissues. Used mainly for infections of the urogenital region, as well as for respiratory infection 200-400 mg 2-3 times a day.
Lomefloxadine (moxaquin) is a difluoroquinnolone. It is quickly and easily absorbed when taken orally. Bioavailability exceeds 98%. It accumulates very well in the tissues of the prostate gland. Use 1 tablet 400 mg per day for respiratory and urinary tract infections, prevention of urogenital infections in the postoperative period, damage to the skin and soft tissues, gastrointestinal tract
Nitrofurans
Nntrofurans are active against gram-positive and gram-negative flora: E. coli, dysentery bacilli, pathogens of paratyphoid fever, salmonella, Vibrio cholerae, Giardia, trnchomonads, staphylococci, large viruses, pathogens are sensitive to them gas gangrene. Drugs in this group are effective against microorganism resistance to other antimicrobial agents. Nntrofurans have antihypertensive activity and rarely cause bacterial infections and candidiasis. The drugs have a bactericidal effect by inhibiting the formation of nucleic acids. They are well absorbed from the gastrointestinal tract, quickly penetrate and are evenly distributed in fluids and tissues. Their main transformation in the body is the restoration of the nucleo group. Nitrofurans and their metabolites are excreted by the kidneys, partly with bile and into the intestinal lumen
Side effects include dyspeptic phenomena and allergic reactions, methemoglobinism, decreased platelet aggregation and, in connection with this, bleeding, disruption of the ovarian-menstrual cycle, embryotoxicity, impaired renal function; with long-term use, neuritis and pulmonary interstitial infiltrates may occur. To prevent side effects it is recommended drinking plenty of fluids, prescription of anti-tungstamine drugs and B vitamins. A large number of side effects limit the use of drugs in this group.
Furazolidone acts against Nashngella, Salmonella, Vibrio cholerae, Giardia, Homonads, Paratyphoid bacilli, Proteus. It is used for gastrointestinal infections. FurazolidoneSy»tchem6
increases sensitivity to alcoholic drinks, that is, it has a teturam-like effect. Prescribed orally after meals, 0.1-0.15 g 4 times a day. It is not recommended to take it for more than 10 days.
Furadonin (nitrofuranton) has an antimicrobial spectrum of action similar to the spectrum of action of furazolndone, but is more active against intestinal papillae, staphylococci and Proteus. When taken orally, furadonna is rapidly absorbed from the gastrointestinal tract. 50% of furadonin is excreted in the urine unchanged, and 50% as inactive; metabolites. High concentrations of the drug in urine persist for up to 12 hours. Furadonn is eliminated in large quantities with bile. The drug penetrates the placenta. The drug is used for infections of the urinary system.
Furogn (solafur) is the most widely used of the drugs in this group. For oral use, a single dose is 0.1-0.2 g, it is taken 3 times a day for 7-10 days. The main use is as a urinary agent. Locally used for rinsing (in surgery) and douching (in obstetric and diarrheal practice).
Thiosemicarbazone derivative
Faringosept (Ambazon) is a bacteriostatic drug, which is a 1,4-benzoquino-guaiyl-hydrozontnosemicarbazone. Active against hemolytic streptococcus, pneumococcus, viridans streptococcus. Indications for use of the drug are limited to diseases of the nasopharynx; treatment and prevention of cataracts, gingivitis, stomatitis caused by pathogens sensitive to this drug, as well as treatment of complications after operations in the nasopharynx. Sublinshaglio is used from 3 to 5 tablets per day 15-30 minutes after meals.
Quinoxaline derivatives
Hnnoxndnn is a quinoxal derivative, a synthetic antibacterial agent. Active against Frieddender's bacillus, Pseudomonas aeruginosa, Escherichia coli and dysentery bacilli, salmonella, staphylococci, clostridium (especially causative agents of gas gangrene). Quinoxidine is indicated for severe forms of inflammatory processes in the abdominal cavity.
In terms of pharmacodynamics and pharmacodynamics, dioxidin is similar to quinoxin, but has less toxicity and the possibility of intracavitary and intravenous administration daoxn-dia significantly increased the effectiveness of the treatment of sepsis, especially caused by staphylococcus and blue-collar daddy.
Sulfanilamide medicines
They are derivatives of sulfanilic acid amide. The chemotherapeutic activity of sulfonamides was discovered in the 30s of the twentieth century, when the German researcher Domagk discovered and proposed for medical use prontosil or red streptocide, for which he was awarded the Nobel Prize.
It was soon discovered that sulfanilic acid amide, which was called white streptocide, has an antimicrobial property in the prontosil molecule. Based on its molecule, a large number of sulfonamide drug derivatives have been synthesized.
The mechanism of action of sulfonamides is associated with specific antagonism with para-aminobenzoic acid (PABA), a factor in the growth and development of microbial cells. PABA is necessary for the synthesis of dihydrofolic acid by microorganisms, which is involved in the further formation of purine and pyrimidine bases, which are necessary for the synthesis of nucleic acids in microorganisms. Due to the similarity of the structure of PABA, sulfonamide drugs displace it and, instead of PABA, are captured by the microbial cell, thereby inhibiting the growth and development of microorganisms. (Fig.28). For getting therapeutic effect sulfonamides must be prescribed in doses sufficient to prevent the possibility of microorganisms using PABA located in the tissues.
The activity of sulfonamides decreases in purulent contents and blood, where high concentrations of PABA are observed. Their activity also decreases in the presence of substances that decompose to form PABA (novocaine, benzocaine, sulfonylurea derivatives), when administered together with folic acid and drugs involved in its synthesis.
Sulfonamides have a bacteriostatic effect. The spectrum of action of these compounds is quite wide and includes the following pathogens: gram-positive and gram-negative bacteria (streptococci, pneumococci, gonococci, meningococci, E. coli, shigella, pathogens of anthrax, plague, diphtheria, brucellosis, cholera, gas gangrene, tularemia), protozoa ( plasmodia malaria, toxoplasma), chlamydia, actinomycetes.
Most sulfonamides are well absorbed from the gastrointestinal tract, mainly into small intestine. Distribution in the body occurs evenly, they are found in cerebrospinal fluid, penetrate into the joint cavity, pass through the placenta.
In the body, sulfonamides undergo acetylation, and their chemotherapeutic activity is lost. Acetyl derivatives are less soluble in water and precipitate. The degree of acetylation for different drugs varies greatly. Sulfonamides are excreted from the body mainly by the kidneys.
Sulfonamide drugs are used to treat infectious diseases different localization. Drugs that are well absorbed from the intestines are used to treat pneumonia, meningitis, sepsis, urinary tract infections, tonsillitis, erysipelas, wound infections etc. They are often used in combination with antibiotics.
Some sulfonamides are poorly absorbed from the intestine, create high concentrations in it and actively suppress intestinal microflora (phthalazol, sulgin, phtazin).
Sulfonamide drugs are considered low-toxic compounds, but can cause the following undesirable side effects: allergic reactions (rash, dermatitis, fever), dyspeptic disorders (nausea, vomiting, loss of appetite), crystalluria (acetylated products can precipitate in the kidneys in the form of crystals and clog the urinary tract ), renal dysfunction, leukopenia, anemia, neuropsychiatric disorders. To prevent crystalluria, it is recommended to drink plenty of alkaline fluids (up to 3 liters per day).
Sulfonamides are contraindicated in cases of hypersensitivity to them, impaired renal excretory function, diseases of the blood system, liver damage, and pregnancy.
Resorptive sulfonamides
These drugs are well absorbed from the gastrointestinal tract, accumulate in all tissues and vary in duration antibacterial effect and the rate of excretion from the body.
PM short acting with a half-life (by 50%) of up to 8 hours. To maintain bacteriostatic concentrations, they are prescribed every 4-6 hours.
Sulfadimezine (sulfamethazine) is practically insoluble in water. Relatively low-toxic, but causes crystalluria and changes in the blood picture.
Sulphaethylthiadiazole (ethazole) is practically insoluble in water. Less acetylated than other sulfonamides, does not cause crystalluria and has less effect on the blood. Etazol sodium is easily soluble in water and can be used parenterally for severe infections.
Sulfacetamide (sulfacyl sodium) is highly soluble in water. It is used locally in ophthalmic practice in the form of drops and ointments for the treatment of conjunctivitis, blepharitis, purulent corneal ulcers, and for the treatment of wounds. It is also used parenterally for systemic action in severe infections.
Sulfanilamide (streptocide) for systemic action is used in tablets and powders, and it is quickly absorbed into the blood. For the treatment of purulent-inflammatory skin diseases, ulcers, wounds, streptocide ointment or streptocide liniment is used topically on the affected skin surface or on dressing napkins. Included in the combined ointments “Sunoref”, “Nitacid”, aerosol “Inhalipt”.
Long-acting drugs with a half-life of up to 24-48 hours. They are well absorbed from the gastrointestinal tract, but are slowly eliminated from the body; they are prescribed 1-2 times a day.
Sulfadimethoxine (Madribon), sulfamethoxazole are significantly reabsorbed in the renal tubules, accumulate in large quantities in bile, penetrate into the pleural fluid, but penetrate poorly and slowly through the blood-brain barrier.
Sulfapyridazine (sulfamethoxypyridazine) is also reabsorbed in the kidneys. Penetrates into the cerebrospinal and pleural fluid, accumulates in bile. Effective against some viruses and protozoa (causative agents of malaria, trachoma, leprosy).
Ultra-long-acting (prolonged) action drugs with a half-life of up to 84 hours.
Sulfamethoxypyridazine (sulfalene) is rapidly absorbed from the gastrointestinal tract, so its high concentrations are created in the intestinal lumen. They are used in the treatment of intestinal infections - bacillary dysentery, colitis, enterocolitis, for the prevention of intestinal infections, in the postoperative period.
Sulfonamides that are not absorbed from the gastrointestinal tract
Phthalylsulfathiazole (phthalazole) is a powder that is practically insoluble in water. In the intestine, the sulfonamide part of the molecule, norsulfazole, is split off. Phthalazole is often combined with antibiotics and well-absorbed sulfonamides. Its toxicity is low and well tolerated. Prescribed 4-6 times a day for intestinal infections.
Sulfaguanidine (sulgin) acts similarly to phthalazole.
Ftazin is a longer-acting drug; it is prescribed 2 times a day for dysentery, salmonellosis and other intestinal infections.
Combination sulfonamide drugs
The most commonly used combination of sulfonamides with trimethoprim. Trimethoprim blocks the conversion of dihydrofolic acid to tetrahydrofolic acid. In such a combination, antimicrobial activity increases and the effect becomes bactericidal. (Fig. 28).
Co-trimaxazole (Biseptol, Septrin, Groseptol, Bactrim, Oriprim, etc.) is a combination of sulfamethoxazole and trimethoprim. The drug is well absorbed from the gastrointestinal tract, the duration of the effect is about 8 hours. It is excreted mainly by the kidneys. Prescribed 2 times a day for respiratory tract infections, intestinal, ENT infections, genitourinary system and etc.
Side effects are the same as other sulfonamides.
Rice. 33 Mechanism of action of sulfonamides and trimethoprim
Similar drugs are Lidaprim (sulfametrol + trimethoprim), Sulfatone (sulfamonomethoxine + trimethoprim).
Drugs have been created that combine sulfonamide and salicylic acid fragments in their structure. These include Salazopyridazine (salazodin), Mesalazine (mesacol, salofalk, etc.). These drugs have antibacterial and anti-inflammatory effects. Used for nonspecific ulcerative colitis and Crohn's disease (granulomatous colitis) orally and rectally. When used, allergic reactions, leukopenia, and anemia are possible.
Nitrofuran derivatives
Nitrofuran derivatives are broad-spectrum antimicrobial agents; they are effective against many gram-positive and gram-negative bacteria, anaerobes, protozoa, rickettsia, and fungi. Pseudomonas aeruginosa, Mycobacterium tuberculosis, and viruses are resistant to them.
Nitrofurans disrupt processes tissue respiration in microorganisms and have a bacteriostatic effect. They are effective when microorganisms are resistant to other antimicrobial agents.
Nitrofurans are well absorbed from the gastrointestinal tract and are distributed approximately evenly in tissues. They penetrate into the cerebrospinal fluid poorly. They are excreted in the urine by the kidneys, partly with bile into the intestinal lumen.
They are used mainly for the treatment of intestinal and urinary tract infections, and some are used topically as antiseptics (furacilin).
The main undesirable side effects resulting from oral nitrofurans include dyspeptic and allergic reactions, dizziness. They have a teturam-like effect (increase the body's sensitivity to alcohol). In order to reduce side effects when taking nitrofuran derivatives, it is recommended to drink plenty of fluids, take drugs after meals, and B vitamins. Contraindicated in serious illnesses kidneys, liver, heart, hypersensitivity to nitrofurans, pregnancy, lactation.
Nitrofurantoin (furadonin) has a wide spectrum of antimicrobial action and is highly active against staphylococcus and Escherichia coli. Found in high concentrations in urine, it is therefore used for urinary tract infections. In addition, furadonin is excreted in the bile and can be used for cholecystitis.
Furazidin (furagin) has a wide spectrum of action. Used for acute and chronic urethritis, cystitis, pyelonephritis and other infections of the urinary tract and kidneys in tablets. For the treatment of purulent wounds, burns, for douching and rinsing, a solution of isotonic sodium chloride solution is used locally.
Furazolidone inhibits the growth and reproduction of gram-positive and gram-negative microorganisms. Poorly absorbed from the gastrointestinal tract. Particularly active against gram-negative microbes, in particular pathogens of intestinal infections. It has anti-trichomonas and anti-giardiasis activity.
Used for intestinal infections, sepsis, trichomonas colpitis, giardiasis, infected burns, etc. Sometimes used to treat alcoholism. Nifuroxazide has the same effect.
Nitrofural (furacilin) is used in the form of aqueous, alcohol solutions, ointments as an antiseptic for treating wounds, rinsing and washing cavities, during purulent-inflammatory processes on the skin. Orally in tablets can be used to treat dysentery and urinary tract infections.
Nitroimidazole derivatives
They exhibit a bactericidal effect against all anaerobes, protozoa, Helicobacter pylori. Inactive against aerobic bacteria and fungi. They are universal antiprotozoal agents. When taken orally, they are quickly and completely absorbed, penetrate into all tissues, including passing through the blood-brain and placental barriers. Metabolized in the liver, excreted in the urine unchanged and in the form of metabolites, coloring it red-brown.
Metronidazole (Trichopol, Flagyl, Klion, Metrogyl) is prescribed for trichomoniasis, giardiasis, extracellular amebiasis, gastric ulcer and other diseases. Prescribed orally, parenterally, rectally, locally.
The most common side effects are dyspeptic symptoms (appetite disturbance, metallic taste, diarrhea, nausea), which can cause disturbances in the central nervous system (impaired coordination of movements, convulsions). It has a teturam-like effect and is not compatible with alcohol.
Nitroimidazole derivatives also include Tinidazole (Fazizhin), Ornidazole (Tiberal), Nimorazole (Naxodzhin). They act longer than metronidazole. Tinidazole is part of a complex drug in combination with norfloxacin “N-Flox-T”. Has antibacterial and antiprotozoal activity.
Quinolones
1st generation - Non-fluoridated
8-hydroxynoline derivatives
Intetrix
Nitroxoline
The drugs have a wide spectrum of antimicrobial action, as well as antifungal and antiprotozoal activity.
The mechanism of antibacterial action is to disrupt the protein synthesis of microbial cells. Hydroxyquinoline drugs are used for intestinal infections, infections of the genitourinary system, etc.
There are 8-hydroxyquinoline derivatives that are poorly absorbed and those that are well absorbed from the gastrointestinal tract.
Intetrix is poorly absorbed from the digestive canal. Effective against most gram-positive and gram-negative pathogenic intestinal bacteria and fungi of the genus Candida. Taken for acute diarrhea, intestinal amebiasis. Low toxic.
Nitroxoline (5-NOK, 5-nitrox) is rapidly absorbed from the gastrointestinal tract and excreted unchanged by the kidneys. Used for urinary tract infections caused by various gram-positive and gram-negative microorganisms. Active against some yeast-like fungi. Prescribed internally. Side effects include dyspepsia and neuritis. When taking nitroxoline, the urine becomes bright yellow.
8-hydroxyquinoline derivatives are contraindicated in case of hypersensitivity to them, impaired renal function, liver function, or damage to the peripheral nervous system.
Naphthyridine derivatives
Nalidixic acid
Pipemidic acid
Nalidixic acid (nevigramon, negram) exhibits a strong antibacterial effect against gram-negative microorganisms. Pseudomonas aeruginosa, gram-positive pathogens and anaerobes are resistant to nalidixic acid.
Depending on the concentration, it acts bactericidal and bacteriostatic. Well absorbed when taken orally, excreted unchanged in urine. Used for urinary tract infections, especially acute forms, as well as for cholecystitis, otitis, enterocolitis.
The drug is usually well tolerated, sometimes dyspeptic disorders, allergic reactions, and photodermatoses are possible.
Nalidixic acid is contraindicated in cases of impaired liver function, kidney function, pregnancy, and children under 2 years of age.
Pipemidic acid (palin, pimidel, pipemidin, pipem) has a bactericidal effect against most gram-negative and some gram-positive microorganisms. It is well absorbed from the gastrointestinal tract and excreted unchanged by the kidneys, creating high concentrations in the urine. Used for acute and chronic diseases urinary tract and kidneys.
Dyspeptic symptoms and allergic reactions in the form of a rash are possible.
2nd generation – fluorinated (fluoroquinolones)
These drugs are quinolone derivatives containing fluorine atoms in their structure. They are highly active antibacterial agents with a wide spectrum of action. Affects bacterial DNA metabolism. They have a bactericidal effect on aerobic gram-negative bacteria, but have a somewhat weaker effect on gram-positive pathogens. Active against mycobacterium tuberculosis and chlamydia.
Fluoroquinolones are well absorbed and effective when taken orally, and are excreted by the kidneys most often unchanged. They penetrate various organs and tissues and pass through the blood-brain barrier.
They are used for severe infections of the urinary tract, kidneys, respiratory tract, gastrointestinal tract, ENT infections, meningitis, tuberculosis, syphilis and other diseases caused by microorganisms sensitive to fluoroquinolones.
The habituation of microorganisms to fluoroquinolones develops relatively slowly.
May cause unwanted side effects: dizziness, insomnia, photosensitivity, leukopenia, changes in cartilage, dysbacteriosis.
Contraindicated during pregnancy, lactation, and under 18 years of age.
1st generation – systemic action:
Ciprofloxacin (tsiprobay, tsifran, tsiprinol), Pefloxacin (abactal), Norfloxacin (norbactin, nolitsin), Ofloxacin (tarivid, oflomax), Lomefloxacin (maxaquin, lomitas) are widely used in urology, pulmonology, ophthalmology, otolaryngology, dermatology for the treatment of infectious diseases of various courses. Used orally, by injection, locally.
2nd generation – respiratory fluoroquinolones:
They selectively accumulate in the respiratory tract. Levofloxacin (Tavanic), Moxifloxacin (Avelox) are used for respiratory tract infections, pulmonary tuberculosis, skin and soft tissues once a day. Effective for infections resistant to β-lactam antibiotics, macrolides and other chemotherapeutic agents. Less likely to cause unwanted effects.
| Drug name, synonyms, storage conditions | Release forms | Methods of application |
| Sulfadimidinum (Sulfadimezinum) (B) | First dose 4 tablets, then 2 tables. in 4 hours |
|
| Sulfanilamidum (Streptocidum) (B) | Table 0.3; 0.5 Ointment 10% – 15.0; 20.0; 30.0; 50.0 Liniment 5% – 30.0 | 1-2 tables each. 5-6 times a day Into the wound cavity Externally on affected areas of skin Externally on affected areas of skin |
| Sulfaaethylthiadizolum (Aethazolum) (B) | Table 0.5 | 2 tables each 4-6 times a day Into the wound cavity |
| Aethazolum-natrium (B) | Amp. 10% and 20% solution – 5 ml and 10 ml | Into a muscle (into a vein) slowly) 3 times a day |
| (Sulfacylum-natrium) (B) | Flak. (tube- dropper) 10%, 20%, 30% solution – 1.5 ml, 5 ml and 10 ml Ointment 30% - 10.0 Amp. 30% solution – 5 ml | 2 drops per cavity conjunctiva 3 times a day Place behind the eyelid 3 times a day Into a vein slowly 2 times a day |
| Sulfadimethoxinum (Madribonum) (B) | Table 0.5 | 1-2 tables each. 1 time per day (1 day – 4 tablets) |
| 1 table each 1 time per day (1 day 5 tablets). at chronic infection 1 table each 1 time per week |
||
| Phthalylsulphathiazidum (Phthalazolum) | Table 0.5 | 2 tables each 4-6 times a day |
| Sulraguanidinum (Sulginum) | Table 0.5 | 2 tablets 4-6 times a day |
| Co-Trimoxazolum Biseptolum, Septrinum, Oriprinum) | Table 0.12; 24; 0.48; 0.96 Susp. 80ml and 100ml | Pa 2 tab. morning and evening after meals 2 teaspoons each spoon 2 times a day 10 ml into a vein 2 times a day |
| Salazopyridazinum (Salazodinum) |
1. Antihelminthics
For intestinal nematodes: mebendazole, albendazole, pyrantel, piperazine, bephenium, levamisole, etc.
For intestinal cestodias: praziquantel, fenasal, etc.
Used for extraintestinal invasions: mebendazole, praziquantel, etc.
2. Antiprotozoal
For malaria: chloroquine, primaquine, pyrimethamine, quinine
For amoebiasis: metronidazole, tinidazole, emetine, quiniophone, chloroquine
For trichomonas: metronidazole, tinidazole
For giardiasis: metronidazole, tinidazole, furazolidone, aminoquinol
For toxoplasmosis : spiramycin, pyrimethamine, sulfonamides
For balantidiasis: tetracycline
For leishmaniasis: solyussurmin
For trypanosomiasis: melarsoprol, primaquine.
Antihelminthics.
More than 2 billion people suffer from helminth infections in the modern world. They are especially widespread in tropical countries, and their globalization is facilitated by tourism, population migration, wars, and other events.
Mebendazole (vermox) - available in tablets of 0.1.
It is a derivative of benzimidazole. The drug is prescribed according to regimens that are individual in cases of each specific helminth. When administered orally, the drug is poorly absorbed. Considering that mebendazole is rapidly destroyed during its first passage through the liver, these pharmacokinetic features provide low bioavailability of the drug with this route of administration, about 22%. In the blood, mebendazole is 95% bound to plasma proteins. The drug is metabolized in the liver to inactive metabolites and is excreted mainly with bile through the intestines. T ½ is about one and a half hours.
The mechanism of action of mebendazole is associated with the suppression of the activity of mitochondrial fumarate reductase of sensitive microorganisms, which slows down glucose transport and oxidative phosphorylation of the corresponding helminths. In addition, the drug can inhibit the assembly of helminth microtubules by binding mebendazole to β-tubulin. Benzimidazole derivatives interact with nematode β-tubulin in lower concentrations than with mammalian β-tubulin, which explains the selectivity of the action of such drugs.
The degree of resistance of nematodes to drugs of this group correlates with the expression of genes of various β-tubulin isotypes, which reduces the resistance of helminths to benzimidazole derivatives. This is due to a point mutation, as a result of which Fen 200 β-tubulin is mixed with tyrosine. And since humans also have tyrosine at the same position of the β-tubulin gene, the new benzimidazole derivatives, toxic to β-tubulin-resistant helminths, probably become toxic to humans.
S.D. SSD: roundworm, pinworm, intestinal hookworm, whipworm, intestinal eelworm, trichinella, echinococcus, etc.
P.P. Ascariasis, enterobiasis (after 2 weeks, repeated deworming is necessary to prevent reinfestation), hookworm disease, trichuriasis, strongyloidiasis, trichinosis, sometimes for echinococcosis, etc.
P.E. Abdominal pain, diarrhea; in case of overdose - inhibition of hematopoiesis, hepatotoxicity; teratogenic effect; individual intolerance.
Thiabendazole acts and is used similarly to mebendazole. Differences: 1) the drug is more quickly and completely absorbed from the gastrointestinal tract, excreted mainly in the urine in the form of metabolites; 2) ineffective against Trichinella; 3) a more toxic agent, P.E. + hallucinations, convulsions; Steven-Johnson syndrome; Individual intolerance most often occurs in the form of anaphylactoid reactions.
Albendazole acts and is used similarly to mebendazole. Differences: 1) the drug binds to plasma proteins by 70%; 2) T ½ ranges from 4 to 15 hours: 3) penetrates well into tissues, incl. in hydrate cysts, therefore more effective for echinococcosis; 4) excreted in urine; 5) has more SSD: + cysticerci, clonorchia, Encephalitozoon intestinali et lieneusi (pathogens of microsporidiosis in patients with AIDS), hookworms of dogs and cats, causing larva migrans syndrome in humans; 6) better tolerated.
Levamisole (decaris) - available in tablets of 0.05 and 0.15.
The drug is prescribed orally, according to regimens individual in cases of each specific helminth. Rapidly absorbed from the gastrointestinal tract. Metabolized in the liver, excreted mainly through the kidneys in the urine. T ½ is about 16 hours.
In humans, the drug can cause an immunomodulatory effect, i.e. suppress the immune system when it is hyperactivated and, conversely, stimulate it during immunosuppression. This mainly concerns the T-link of the immune system.
O.E. 1) Antihelminthic, S.D.: roundworm, pinworm, intestinal crooked head, trichostrongyloid, American necator, whipworm, toxoplasma, etc.
2) Immunomodulatory.
P.P. Ascariasis, enterobiasis (after 2 weeks, repeated deworming is necessary to prevent reinfestation), hookworm disease, trichostrongyloidiasis, necatoriasis, trichocephalosis, toxoplasmosis.
P.E. Nausea, vomiting, diarrhea; stomatitis; headache, dizziness, central nervous system stimulation to hallucinations and convulsions; inhibition of hematopoiesis; nephrotoxicity; allergies.
Bethenius (naftamon, naftamon K, alcopar) - available in tablets of 0.5.
It is practically not absorbed from the gastrointestinal tract and acts in the intestinal lumen. Moreover, the naphthamon K shell disintegrates mainly in the small intestine, providing a local effect there. But naphthamon simply exerts its predominant effect in the lumen of the large intestine.
S.D. Ascaris, pinworm, intestinal crooked head, trichostrongyloides, whipworm.
P.P. Ascariasis, enterobiasis (repeated deworming is necessary after 2 weeks to prevent reinfestation), hookworm disease, trichostrongyloidiasis, trichocephalosis.
P.E. Nausea, vomiting, diarrhea; sometimes - hepatotoxicity; allergies.
Pirantel (combantrin) - available in tablets of 0.25.
The drug is prescribed according to regimens that are individual in cases of each specific helminth. The drug is poorly absorbed from the gastrointestinal tract, therefore, it is especially effective for intestinal nematodes. Most of the pyrantel is excreted in feces, almost 50% unchanged, about 15% of the applied dose is excreted from the patient’s body in the urine.
Pyrantel is a depolarizing muscle relaxant. It opens cation channels and thereby causes persistent stimulation of H - cholinergic receptors. As a result, spastic paralysis occurs in helminths, and the ability of the drug to suppress the activity of acetylcholinesterase also contributes to this. That is why pyrantel should not be combined, for example, with piperazine, which, on the contrary, has the opposite effect on the muscles of helminths, as well as with other drugs of the same type of action. As a result of the above, helminths are expelled from the gastrointestinal tract due to its peristalsis. Pregnant women and children under 2 years of age are not recommended to use pyrantel.
S.D. Ascaris, pinworm, intestinal hookworm, trichostrongyloides, American necator, etc.
P.P. Ascariasis, enterobiasis (after 2 weeks, repeated deworming is necessary to prevent reinfestation), hookworm disease, trichostrongyloidiasis, necatoriasis, etc.
P.E. Nausea, vomiting, diarrhea; headache, dizziness; skin rashes; fever.
Piperazine adipate - Available in tablets of 0.2 and 0.5.
The drug is prescribed orally, according to regimens individual in cases of each specific helminth. Piperazine is quickly and completely absorbed from the gastrointestinal tract, excreted in the urine, and up to 20% of the prescribed dose is excreted unchanged.
Under the influence of piperazine, sensitive roundworms experience flaccid paralysis and are expelled from the gastrointestinal tract due to its peristalsis. The drug acts as a GABA agonist: it increases the chlorine permeability of the membranes of roundworm muscle cells, resulting in hyperpolarization of the membranes, which reduces the excitability of the cells, leading to muscle relaxation and flaccid paralysis. Therefore, unlike pyrantel, piperazine is relatively safe when used in pregnant women and children.
S.D. Ascaris, pinworm.
P.P. Ascariasis, enterobiasis (after 2 weeks, repeated deworming is necessary to prevent reinfestation).
P.E. Nausea, vomiting, diarrhea; headache, dizziness; in case of severe overdose - convulsions, respiratory depression; allergies.
Praziquantel (biltricide, azinox) - available in tablets of 0.6.
The drug is prescribed orally, according to regimens individual in cases of each specific helminth. With this route of administration, the drug is absorbed quickly and almost completely (by 80%), but the bioavailability of the drug is low, because a significant part of the dose taken is biotransformed in the liver during the first passage of the drug through it with the formation of inactive or low-active hydroxylated or conjugated metabolites. In the blood, praziquantel is 80% bound to plasma proteins. Almost 70% of the dose taken is excreted in the urine in the form of metabolites within 24 hours, the rest is excreted in bile through the intestines. T ½ is about 1.5 hours for the drug and 4 - 6 hours for its metabolites.
Even in minimal doses, praziquantel increases the muscle tone of helminths sensitive to it, causing them to have prolonged muscle contractions and the phenomenon of spastic paralysis. In higher doses, the drug causes the destruction of the tegument of helminths, which exposes their antigens and triggers the immune response of the sick person.
S.D. Bovine tapeworm, pork tapeworm and cysticerci, dwarf tapeworm, broad tapeworm, cat fluke, Chinese and lung flukes, schistosomes, metagonima, paragonima, intestinal eel.
P.P. Opisthorchiasis, schistosomiasis, clonarchiasis, meta- and paragonism, taeniasis and sometimes with cystecircosis, taeniarinchiasis, hymenolepiasis, diphyllobothriasis, strongyloidiasis.
P.E. Nausea, vomiting; headache, dizziness, fatigue; allergies; muscle and joint pain; stimulation of the central nervous system to the point of convulsions; teratogenic.
Fenasal (niclosamide) acts and is used similarly to praziquantel. Differences: 1) has a narrower spectrum of action, used only for taeniasis, teniarynchosis, diphyllobothriasis, hymenolepiasis; 2) more cheap remedy; 3) a less active and more toxic agent.
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