Iron preparations during pregnancy

Sulfonamides are first class AMP for widespread use. In recent years, the use of sulfonamides in clinical practice has decreased significantly since they are significantly inferior in activity to modern antibiotics and are highly toxic. Significant is the fact that due to the long-term use of sulfonamides, most microorganisms have developed resistance to them.

Mechanism of action

Sulfonamides have a bacteriostatic effect. Being chemical analogues of PABA, they competitively inhibit the bacterial enzyme responsible for the synthesis of dihydrofolic acid, a precursor of folic acid, which is the most important factor in the activity of microorganisms. In environments containing a large amount of PABA, such as pus or tissue decomposition products, the antimicrobial effect of sulfonamides is significantly weakened.

Some topical sulfonamide preparations contain silver (silver sulfadiazine, silver sulfathiazole). As a result of dissociation, silver ions are slowly released, exerting a bactericidal effect (due to binding to DNA), which does not depend on the concentration of PABA at the site of application. Therefore, the effect of these drugs is preserved in the presence of pus and necrotic tissue.

Activity spectrum

Initially, sulfonamides were active against a wide range of gram-positive (

Currently, many strains of staphylococci, streptococci, pneumococci, gonococci, meningococci, enterobacteria are characterized by a high level of acquired resistance. Enterococci, Pseudomonas aeruginosa and most anaerobes are naturally resistant.

Drugs containing silver are active against many pathogens of wound infections – Staphylococcus spp.,

Pharmacokinetics

Sulfonamides are well absorbed in the digestive tract (70-100%). Higher blood concentrations are observed when using drugs of short (sulfadimidine, etc.) and medium duration (sulfadiazine, sulfamethoxazole) action. Sulfonamides of a long-term (sulfadimethoxin, etc.) and long-lasting (sulfalene, sulfadoxine) actions are associated with blood plasma proteins to a greater extent.

They are widely distributed in tissues and body fluids, including pleural effusion, peritoneal and synovial fluids, middle ear exudate, chamber moisture, tissues of the urogenital tract. Sulfadiazine and sulfadimethoxine pass through the BBB, reaching 32-65% and 14-30% serum concentrations in CSF, respectively. Pass through the placenta and enter the breast milk.

Metabolized in the liver, mainly by acetylation, with the formation of microbiologically inactive, but toxic metabolites. Excreted by the kidneys approximately half unchanged, with alkaline urine excretion increases; small amounts are excreted in the bile. In renal insufficiency, the accumulation of sulfonamides and their metabolites in the body is possible, leading to the development of a toxic effect.

In the local application of sulfonamides containing silver, high local concentrations of active ingredients are created. Systemic absorption through the damaged (wound, burn) surface of the sulfonamide skin can reach 10%, silver – 1%.

Unwanted reactions

Systemic drugs

Allergic reactions: fever, skin rash, itching, Stevens-Johnson and Lyell syndromes (more often with the use of long-acting and long-lasting sulfonamides).

Hematological reactions: leukopenia, agranulocytosis, hypoplastic anemia, thrombocytopenia, pancytopenia.

Liver: hepatitis, toxic dystrophy.

CNS: headache, dizziness, lethargy, confusion, disorientation, euphoria, hallucinations, depression.

GIT: abdominal pain, anorexia, nausea, vomiting, diarrhea, pseudomembranous colitis.

Kidneys: crystalluria, hematuria, interstitial nephritis, tubular necrosis. Crystalluria is often caused by poorly soluble sulfanilamides (sulfadiazine, sulfadimethoxin, sulfalene).

Thyroid gland: dysfunction, goiter.

Other: photosensitivity (increased sensitivity of the skin to sunlight).

Local preparations

Local reactions: burning, itching, pain at the site of application (usually short-term).

Systemic reactions: allergic reactions, rash, skin flushing, rhinitis, bronchospasm; leukopenia (with prolonged use on large surfaces).

Systemic drugs

Toxoplasmosis (usually sulfadiazine in combination with pyrimethamine).

Chloroquine Resistant Malaria

Local preparations

Contraindications

Allergic reactions to sulfa drugs, furosemide, thiazide diuretics, carbonic anhydrase inhibitors and sulfonylurea derivatives.

It should not be used in children up to 2 months. An exception is congenital toxoplasmosis, in which sulfonamides are used for health reasons.

Severe abnormal liver function.

Warnings

Allergy. It is a cross to all sulfa drugs. Given the similarity of the chemical structure, sulfonamides cannot be used in patients allergic to furosemide, thiazide diuretics, carbonic anhydrase inhibitors and sulfonylurea derivatives.

Pregnancy. Since sulfonamides pass through the placenta, and in animal studies have revealed their adverse effects on the fetus, use during pregnancy is not recommended.

Lactation. Sulfonamides penetrate into breast milk and can cause nuclear jaundice in breastfed babies, as well as hemolytic anemia in children with glucose-6-phosphate dehydrogenase deficiency.

Pediatrics. Sulfonamides compete with bilirubin for binding to plasma proteins, increasing the risk of developing nuclear jaundice in newborns. In addition, since liver enzyme systems are not fully formed in the newborn, elevated concentrations of free sulfanilamide may further increase the risk of nuclear jaundice. Therefore, sulfonamides are contraindicated in children up to 2 months. An exception is congenital toxoplasmosis, in which sulfonamides are used for health reasons.

Geriatrics. In the elderly, there is an increased risk of severe undesirable skin reactions, hematopoietic depression, thrombocytopenic purpura (the latter especially when combined with thiazide diuretics). Requires strict control. If possible, avoid the appointment of sulfonamides to patients over 65 years of age.

Impaired renal function. Slowing of renal excretion leads to the accumulation of sulfonamides and their metabolites in the body, which significantly increases the risk of toxic action. In particular, nephrotoxic reactions can intensify up to the development of severe interstitial nephritis and necrosis of the renal tubules. Therefore, sulfonamides should not be used in renal failure.

Liver dysfunction. Slowing the metabolism of sulfonamides with an increased risk of toxic action. Possible development of toxic liver dystrophy. Sulfonamides are contraindicated in severe hepatic pathology.

Pathological changes in the blood. The risk of hematological adverse reactions increases.

Deficiency of glucose-6-phosphate dehydrogenase. High risk of hemolytic anemia.

Porphyria. Perhaps the development of an acute attack of porphyria.

Local application. With prolonged use or application on large surfaces of the skin, it is necessary to control the function of the kidneys, liver and the picture of peripheral blood.

Drug interactions

Sulfonamides can enhance the effect and / or toxic effect of indirect anticoagulants (coumarin or indandion derivatives), anticonvulsants (hydantoin derivatives), oral antidiabetic agents and methotrexate due to their displacement from the connection with proteins and / or weakening their metabolism.

With simultaneous use with other drugs that cause bone marrow depression, hemolysis, hepatotoxic effects, the risk of toxic effects may increase.

When combined with sulfonamides, the effect of estrogen-containing contraceptives can be weakened and the frequency of uterine bleeding may increase.

With the simultaneous use of cyclosporine may increase its metabolism, accompanied by a decrease in serum concentrations and effectiveness. At the same time, the risk of nephrotoxic action increases.

It is not recommended to use simultaneously sulfonamides and methenamine (hexamine) due to the increased risk of crystalluria in the acid reaction of urine.

Phenylbutazone (butadion), salicylates, and indomethacin can displace sulfonamides from their association with plasma proteins, increasing their concentration in the blood.

Patient Information

Sulfonamide drugs must be taken on an empty stomach with a full glass of water; The amount of fluid consumed (preferably alkaline drink) should be sufficient to maintain diuresis at a level of at least 1.2 liters per day for an adult. When applied topically, plenty of drink is also necessary.

Observe the mode of appointment during the entire course of treatment, do not skip the dose and take it at regular intervals. If you miss a dose, take it as soon as possible; Do not take if it is almost time to take the next dose; do not double the dose.

Do not be exposed to direct sunlight and avoid ultraviolet radiation.

Exercise caution if dizziness occurs.

Use caution when using toothbrushes, dental floss and toothpicks; postpone dental surgery.

Consult a doctor if improvement does not occur within a few days or new symptoms appear.

Co-trimoxazole

Combined antimicrobial drug, consisting of 5 parts of sulfamethoxazole (which is sulfanilamide of average duration) and 1 part of trimethoprim. When it was created, it was calculated on the synergistic effect of the components. However, it turned out that when combining trimethoprim with sulfamethoxazole at a ratio of 1: 5, synergy can only be achieved in vitro, while in clinical use it practically does not manifest itself. According to modern concepts, the activity of co-trimoxazole is determined mainly by the presence of trimethoprim. Sulfanilamide component is only important in pneumocystic pneumonia, toxoplasmosis and nocardiosis, and in most clinical situations, its presence determines the risk of adverse reactions characteristic of sulfanilamides.

Mechanism of action

Sulfamethoxazole competitively replaces PABA and prevents the formation of dihydrofolic acid. Trimethoprim, in turn, blocks the next stage of folic acid metabolism, disrupting the formation of tetrahydrofolic acid. Co-trimoxazole has a bactericidal effect.

Activity spectrum

Co-trimoxazole is active against many gram-positive and gram-negative aerobic microorganisms. Staphylococci are sensitive (including some methicillin-resistant strains), pneumococci, some streptococcal strains. Of the gram-negative cocci, meningococci are most sensitive and

Co-trimoxazole acts on a variety of enterobacteria, such as

According to a study conducted in 1998-2000, more than 60% of strains are resistant to co-trimoxazole in Russia

Enterococci, Pseudomonas aeruginosa, many gonococci and anaerobes have a natural resistance.

Pharmacokinetics

After ingestion is well absorbed in the digestive tract. Bioavailability – 90-100%. The maximum plasma concentration is reached in 2-4 hours. It penetrates the BBB, especially during inflammation of the membranes. The components of co-trimoxazole (trimethoprim and sulfamethoxazole) are bound to plasma proteins by 45% and 60%, respectively. Partially metabolized by the liver, excreted mainly by the kidneys in unchanged form, in a small amount – with bile. The average half-life of both components is about 10 hours. In case of renal failure, their accumulation in the body is possible.

Unwanted reactions

Gastrointestinal tract: abdominal pain, nausea, vomiting, diarrhea, pseudomembranous colitis.

Allergic reactions: rash, Stevens-Johnson syndrome, Lyell’s syndrome.

Hematologic reactions: neutropenia, thrombocytopenia, anemia, methemoglobinemia.

Liver: cholestatic hepatitis.

CNS: headache, mental disorders, aseptic meningitis (the latter especially in patients with collagenosis).

Kidneys: crystalluria, hematuria, interstitial nephritis, renal tubular necrosis.

Metabolic disorders: goiter, thyroid dysfunction, hypoglycemia, hyperkalemia.

Local reactions: thrombophlebitis (with a / in the introduction).

Intestinal infections: shigellosis, salmonellosis, travelers’ diarrhea (in regions with low levels of resistance).

Community-acquired infections MEP: acute cystitis, chronic recurrent cystitis, pyelonephritis (in regions with low levels of resistance).

Infections caused by

Pneumocystis pneumonia (treatment and prevention).

Contraindications

Allergic reactions to sulfa drugs, furosemide, thiazide diuretics, carbonic anhydrase inhibitors, sulfonylurea preparations.

It should not be used in children under 2 months, except for children born to HIV-infected mothers.

Severe renal failure.

Severe abnormal liver function.

Megaloblastic anemia associated with folic acid deficiency.

Warnings

Allergy. If any rash appears during the application of co-trimoxazole, it should be immediately canceled in order to avoid the development of severe skin-toxic-allergic reactions. Co-trimoxazole should not be used in patients allergic to furosemide, thiazide diuretics, carbonic anhydrase inhibitors and sulfonylurea derivatives.

Pregnancy. The use of co-trimoxazole during pregnancy (especially in I and III trimesters) is not recommended, since the sulfa component can cause nuclear jaundice and hemolytic anemia, and trimethoprim disrupts the metabolism of folic acid.

Lactation. Sulfamethoxazole penetrates into breast milk and can cause nuclear jaundice in breastfed babies, as well as hemolytic anemia in children with glucose-6-phosphate dehydrogenase deficiency. Trimethoprim disrupts the metabolism of folic acid.

Pediatrics. Sulfonamides compete with bilirubin for binding to plasma white proteins, increasing the risk of developing nuclear jaundice in newborns. In addition, since liver enzyme systems are not fully formed in the newborn, elevated concentrations of free sulfamethoxazole may further increase the risk of nuclear jaundice. In this regard, sulfonamides are contraindicated in children up to 2 months. However, co-trimoxazole can be used in children from 4-6 weeks of age who were born to HIV-infected mothers.

Geriatrics. In older people, there is an increased risk of severe unwanted skin reactions, generalized hematopoietic depression, thrombocytopenic purpura (the latter especially when combined with thiazide diuretics). In case of impaired renal function, the risk of hyperkalemia increases. Strict control is required and, if possible, long courses of co-trimoxazole should be avoided.

Impaired renal function. Slowing of renal excretion leads to the accumulation of co-trimoxazole components in the body, which increases the risk of toxic action. Co-trimoxazole should not be used for severe renal failure (creatinine clearance less than 15 ml / min). If kidney damage occurs, the risk of hyperkalemia increases.

Liver dysfunction. Slowing the metabolism of sulfonamides with an increased risk of toxic action. Possible development of toxic liver dystrophy.

Iron preparations during pregnancy

Dysfunction of the thyroid gland. Care is required when using in connection with the possible exacerbation of thyroid dysfunction.

Hyperkalemia. The component of co-trimoxazole – trimethoprim can cause hyperkalemia, the risk of which is increased in the elderly, in violation of kidney function, while the use of potassium or potassium-sparing diuretics. In these patient groups, the content of potassium in the blood serum should be monitored, and in the event of the development of hyperkalemia, co-trimoxazole should be abolished.

Pathological changes in the blood. The risk of hematological adverse reactions increases.

Deficiency of glucose-6-phosphate dehydrogenase. High risk of hemolytic anemia.

Porphyria. Perhaps the development of an acute attack of porphyria.

Patients with AIDS. The risk of adverse reactions increases significantly in patients with AIDS.

Drug interactions

The sulfanilamide component may enhance the effect and / or toxic effect of indirect anticoagulants (K-marin or indandion derivatives), anticonvulsants (hydantoin derivatives), oral anti-diabetic drugs and methotrexate due to their displacement from the connection with proteins and / or weakening of their metabolism.

With simultaneous use with other drugs that cause bone marrow depression, hemolysis, hepatotoxic effect, the risk of the development of corresponding toxic effects may increase.

When combined with co-trimoxazole, the effect of oral contraceptives may be weakened and the frequency of uterine bleeding may increase.

With simultaneous use of cyclosporine may increase its metabolism, accompanied by a decrease in serum concentrations and effectiveness. At the same time, the risk of nephrotoxic action increases.

Phenylbutazone, salicylates and indomethacin can displace the sulfanilamide component from its association with plasma proteins, thereby increasing its concentration in the blood.

It should not be combined with penicillins, as sulfonamides weaken their bactericidal effect.

Patient Information

Co-trimoxazole must be taken on an empty stomach with a full glass of water. Proper use of liquid dosage forms for oral administration (suspension, syrup).

Strictly observe the regimen of administration during the entire course of treatment, do not skip the dose and take it at regular intervals. If you miss a dose, take it as soon as possible; Do not take if it is almost time to take the next dose; do not double the dose.

Do not use expired or decomposed products as they may be toxic.

You must consult your doctor if improvement does not occur within a few days or new symptoms appear.

Do not take any other drugs without consulting a doctor during co-trimoxazole treatment.

Follow the rules of storage, keep out of reach of children.

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