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The antibiotic tetracycline
Semisynthetic tetracycline, bacteriostatic broad-spectrum antibiotic. Penetrating inside the cell, acts on intracellular pathogens located. It inhibits protein synthesis in the microbial cell, breaks communication transport of aminoacyl tRNA to the 30S ribosomal subunit of the membrane.
To this highly sensitive Gram-positive bacteria: Staphylococcus spp. (including Staphylococcus aureus, Staphylococcus epidermidis), Streptococcus spp. (including Streptococcus pneumoniae), Clostridium spp., Listeria spp .; Actinomyces israeli; and gram-negative organisms: Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae, Klebsiella spp., Escherichia coli, Shigella spp., Enterobacter, Salmonella spp., Bordetella pertussis. Bacteroides spp., Treponema spp. (including strains resistant to others. antibiotics, such as penicillins and cephalosporins date). The most susceptible Haemophilus influenzae (91-96%) and intracellular pathogens.
Doxycycline is active against most dangerous infectious diseases: plague (Yersinia spp.), Tularemia (Francisella tularensis), anthrax bacteria (Bacillus anthracis), Legionella (Legionella spp.), Brucella (Brucella spp.), Cholera (Vibrio cholera) , Rickettsia (Rickettsia spp.), glanders pathogens (Actinobacillus mallei), chlamydia (pathogens psittacosis (Chlamydia psittaci), psittacosis (Rickettsiaformis psittacosi), trachoma (Chlamydia trachomatis ;, venereal granuloma (Calymmatobacterium granulomatis), malaria (Plasmodium falciparum), amoebic dysentery (Entamoeba histolytica).
He acts on most strains of Proteus, Pseudomonas aeruginosa, and fungi.
To a lesser degree than other tetracycline antibiotics inhibits intestinal flora which is different from the more complete absorption and longer duration of action. According to the degree of antibacterial activity of doxycycline superior natural tetracyclines. In contrast to tetracycline and oxytetracycline has a higher therapeutic efficiency, manifested by treatment in 10-fold lower doses and longer duration of action. There is cross-resistance to other tetracyclines and penicillin.
Absorption – fast and high (nearly 100%). Food intake does not significantly influence the extent of absorption. It has high lipid solubility and low affinity binding of calcium ions (Ca2 +). Following oral administration of 200 mg of time to reach maximum plasma concentration – 2.5 h, the maximum plasma concentration – 2.5 mg / ml at 24 hours after administration – 1.25 g / ml.
Relationship to plasma proteins – 80-93%. Well into the organs and tissues; 30-45 minutes after ingestion found in therapeutic concentrations in the liver, kidney, lung, spleen, bones, teeth, prostate, eye tissues, pleural and ascites fluid, bile, synovial exudate, exudate maxillary and frontal sinuses, in the liquid sulcus. Penetrates poorly into cerebrospinal fluid (10-20% of plasma levels). It penetrates through the placental barrier, determined in breast milk. The volume of distribution – 0.7 l / kg.
It is metabolized in the liver of 30-60%. Half-life of – 10-16 hrs (mainly – 12-14 hours on average – 16.3 h). Repeated administration of the drug may accumulate. It accumulates in the reticuloendothelial system and bone. The bones and teeth forms insoluble complexes with ions of calcium (Ca2 +). Excreted in the bile, which is found in high concentrations. Treated enterohepatic recycling output intestine (20-60%); 40% of the dose is excreted by the kidneys within 72 hours (of which 20-50% – unchanged), with severe chronic renal failure – only 1-5%.
In patients with impaired renal function or azotemia is an important route of elimination gastrointestinal secretion.
Inside, adults and children over 12 years weighing more than 45 kg of average daily dose – 200 mg on the first day (divided into 2 doses – 100 mg 2 times a day), followed by 100 mg / day.
In chronic infections of the urinary system – 200 mg / day throughout the treatment period.
In the treatment of gonorrhea appoint one of the following schemes: acute uncomplicated urethritis – course dose of 500 mg (1 reception – 300 mg, the next 2 – 100 mg every 6 hours) or 100 mg / day until complete healing (women), or 100 mg 2 times a day for 7 days (males); in complicated forms of gonorrhea course dose -800-900 mg, which is distributed on 6-7 receptions (300 mg – 1 reception, and then every 6 hours for 5-6 later).
In the treatment of syphilis – 300 mg / day for at least 10 days.
In uncomplicated infections of the urethra, cervix and colon caused by Chlamydia trachomatis, administered at 100 mg two times a day for at least 7 days.
Infections of the male reproductive organs – 100 mg 2 times a day for 4 weeks. Treatment of malaria resistant to chloroquine, – 200 mg / day for 7 days (in conjunction with shizontotsidnymi drugs – quinine); malaria prevention -100 1 mg once a day for 1-2 days before the trip, then daily during the trip and for 4 weeks after return;
Diarrhea “travelers” (prevention) – 200 mg on the first day of the trip (1 reception or 100 mg 2 times a day) 100 mg 1 time per day during their stay in the region (no more than 3 weeks).
Treatment of leptospirosis – 100 mg orally 2 times a day for 7 days; prevention of leptospirosis – 200 mg 1 time per week for staying in disadvantaged areas and 200 mg at the end of the trip.
Preventing infections after medical abortion – 100 mg for 1 h before treatment and 200 mg – 30 minutes after.
When acne – 100 mg / day, the course – 6-12 weeks.
The maximum daily dose for adults – 300 mg / day or 600 mg / day for 5 days with severe gonococcal infections.
If you have severe liver failure requires reduction of the daily dose of doxycycline, as this is a gradual accumulation of it in the body (the risk of hepatotoxicity).
Symptoms: If high doses, especially in patients with impaired liver function may cause neurotoxic reactions, dizziness, nausea, vomiting, seizures, impaired consciousness due to increased intracranial pressure.
Treatment: removal of the drug, gastric lavage with activated charcoal, symptomatic therapy, orally administered antacid and magnesium sulphate to prevent the absorption of doxycycline. There is no specific antidote. Hemodialysis and peritoneal dialysis are ineffective.
Absorbance decrease antacids containing salts of aluminum (Al3 +), calcium (Ca2 +) and magnesium (Mg2 +), preparations of iron (Fe), sodium hydrogen carbonate, laxatives containing magnesium salt (Mg2 +), cholestyramine and colestipol, and therefore their use must be divided at 3 hour intervals.
Due to suppression of intestinal microflora reduces the prothrombin index, which require dose adjustment of indirect anticoagulants.
When combined with antibacterial antibiotics disturb the cell wall synthesis (penicillins, cephalosporins), the effectiveness of the latter decreases. It reduces the reliability of contraception and increases the frequency of bleeding “breakthrough” in patients receiving oral contraceptives estrogensoderjath.
Ethanol, barbiturates, rifampicin, carbamazepine, phenytoin, and others. Stimulants microsomal oxidation accelerating metabolism doxycycline reduce its concentration in plasma.
In an application with methoxyflurane may develop acute renal failure or death.
Simultaneous application of retinol improves intracranial pressure.
Pregnancy and lactation
Use of the drug during pregnancy is contraindicated because, penetrating through the placenta, the drug can disrupt the normal development of the teeth, cause inhibition of growth of bones of the fetus and cause fatty liver.
During lactation the use of doxycycline is contraindicated. If necessary, the drug, the period of treatment should discontinue breastfeeding.
From the nervous system: a benign intracranial hypertension (decreased appetite, vomiting, headache, swelling of the optic nerve), a toxic effect on the central nervous system (dizziness or instability)
Metabolic disorders: anorexia.
From the hearing and vestibular: tinnitus.
For part of the vision: blurred vision, diplopia, scotoma, and as a result of increased intracranial pressure.
From the digestive system: nausea, constipation or diarrhea, abdominal pain, glossitis, dysphagia, esophagitis (including erosive) gastritis, ulceration of the stomach and duodenum 12, pseudomembranous colitis, enterocolitis (due to the proliferation of drug-resistant strains of staphylococci ).
Allergic reactions: maculopapular rash, pruritus, flushing of the skin, angioedema, anaphylactoid reactions, drug lupus, erythematous rash, exfoliative dermatitis, urticaria, anaphylaxis, anaphylactic shock, anaphylactoid reactions, Stevens-Johnson syndrome.
Cardio-vascular system: pericarditis, lower blood pressure, tachycardia, erythema multiforme.
From the side of hematopoiesis: hemolytic anemia, thrombocytopenia, neutropenia, leukopenia, eosinophilia, decrease in prothrombin index.
On the part of the hepatobiliary system: abnormal liver function, increased liver enzymes, autoimmune hepatitis, cholestasis.
Musculoskeletal: arthralgia, myalgia.
Violation of the kidney and urinary tract: increased BUN.
Other: photosensitivity, superinfection; stable discoloration of tooth enamel, inflammation in the anogenital area. Candidiasis (vaginitis, glossitis, stomatitis, proctitis), goiter, a syndrome similar to serum sickness, toxic epidermal necrolysis.
Conditions and terms
In a dry, dark place at a temperature no higher than 25 ° C. Keep out of the reach of children. Shelf life – 4 years.
– Infectious and inflammatory diseases caused by susceptible organisms: respiratory infections (pharyngitis, bronchitis, acute and chronic, tracheitis, bronchopneumonia, lobar pneumonia, lung abscess, empyema);
– Upper respiratory tract infections (otitis, tonsillitis, sinusitis, etc.);
– Infections of the genitourinary system (cystitis, pyelonephritis, prostatitis, urethritis, urethrocystitis, urogenital mycoplasmosis, endometritis, endocervicitis acute orhiepididimit, gonorrhea);
– Infections of the biliary tract and the gastrointestinal tract (cholecystitis, cholangitis, gastroenterocolitis, bacillary dysentery, diarrhea, “traveler”); infections of skin and soft tissue (cellulitis, abscesses, furunculosis, whitlow, infected burns, wounds, and others.);
– Infectious eye disease, syphilis, yaws, yersiniosis, legionellosis, rickettsial disease, chlamydia different localization (including prostatitis, proctitis), Q fever, Rocky Mountain spotted fever, typhus (including typhus, tick, return) Lyme disease (I st. – erythema migrans), bacillary and amoebic dysentery, tularemia, cholera, actinomycosis, malaria; in a combination therapy – leptospirosis, trachoma, psittacosis, psittacosis, granulocytic ehrlichiosis; whooping cough, brucellosis, osteomyelitis; sepsis, subacute bacterial endocarditis, peritonitis;
– Prevention of postoperative septic complications; Malaria, caused by Plasmodium falciparum, during short trips (less than 4 months) in an area where common strains resistant to chloroquine and / or pyrimethamine-sulfadoxine;
– As a drug “first” number is assigned to 65 patients during exacerbation of chronic bronchitis (including on the background of asthma) without concomitant diseases (these are often caused by acute Haemophilus influenzae). Effective with the exacerbation of bronchopulmonary infection (usually staphylococcal etiology) in patients with cystic fibrosis, chlamydial arthritis, granulocytic ehrlichiosis. Older patients used for acute treatment of prostate and urinary infection caused by Escherichia coli.
– Hypersensitivity to doxycycline, the drug, other tetracyclines;
– Lactase deficiency;
– Lactose intolerance;
– Galactose malabsorption glucose;
– Severe hepatic impairment;
– Children’s age (up to 12 years – the possibility of the formation of insoluble complexes with calcium ions (Ca 2+) deposition in the bone skeleton, enamel and dentin of the teeth);
– Children over the age of 12 years with a body weight up to 45 kg.
To prevent irritant action (esophagitis, gastritis, ulceration of the mucosa of the gastrointestinal tract) is recommended reception in the daytime with many liquid food. In connection with the possible development of photosensitivity need to limit sun exposure during treatment and 4-5 days after it. With prolonged use, requires periodic monitoring of liver function of the blood. May mask the symptoms of syphilis, in connection with the possibility of mixed infection is necessary to monthly serological analysis for 4 months. All tetracyclines form stable complexes with ions of calcium (Ca2 +) in any kostnoobrazuyuschey tissue. In this connection, in the reception period of tooth development may cause lasting tooth staining in the yellow-gray-brown color, as well as hypoplasia of enamel. Perhaps falsely elevated levels of catecholamines in the urine when determining the fluorescence method. When biopsy thyroid gland in patients receiving long-term doxycycline may dark brown staining tissue slides without disrupting its function.
The experiment found that doxycycline may have a toxic effect on fetal development (delayed skeletal development) – Blocks metalloproteinases (enzymes that catalyze the degradation of collagen and proteoglycans) in the cartilage, reduces lesions in deforming osteoarthritis. After increasing the dose above 4 g pharmacokinetics of doxycycline is not dependent on the dose and blood concentration does not increase.
When applying the preparation, while receiving and 2-3 weeks after cessation of treatment may develop diarrhea caused by Clostridium difficile. In mild cases enough to discontinuation of treatment and the use of ion exchange resins (cholestyramine, colestipol), in severe cases, loss of refund shown fluid, electrolytes and protein, the appointment of vancomycin, metronidazole or bacitracin. Do not use medicines which inhibit peristalsis.
Effects on ability to drive vehicles and management mechanisms
Patients should refrain from all activities that require attention, rapid mental and motor.
If abnormal liver function
Contraindicated in severe hepatic insufficiency. If you have severe liver failure requires reduction of the daily dose of doxycycline, as this is a gradual accumulation of it in the body (the risk of hepatotoxicity).
Application in childhood
It is contraindicated in children under 12 years (possibility of forming insoluble complexes with calcium ions (Ca 2+) deposition in the bone skeleton, enamel and dentin of the teeth); and children after the age of 12 years with a body weight up to 45 kg.
Application is possible in children over 12 years weighing more than 45 kg according to the dosage regimen.
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