Doxycycline monohydrate in rheumatology: problems and prospects
In the coming XXI century Infectious diseases remain one of the most significant medical problems. In rheumatology the urgency of this issue is caused by at least two factors. It is now well known and proved the role of infectious agents in the development of rheumatic diseases (RD) in which microorganisms play a triggering role in triggering inflammatory immunopathological mechanisms. Equally challenging is the fight against co-infection, is often complicated for many RH.
Despite the extensive arsenal of antimicrobial agents, developed and introduced into clinical practice in the second half of the last century, infectious pathology rational therapy issues still need to imagine the most attention as the medical scientists and practitioners of various specialties. Identification of new pathogens, the growing role of conditionally pathogenic microflora, increase in the number of resistant organisms, the inferiority of the immune response, tolerability issues and interactions with anti-rheumatic drugs, pharmacoeconomic aspects - all this requires constant awareness rheumatologist about the basic principles of rational therapy of bacterial infections in RA.
The emergence of new antibacterial agents in recent years has greatly increased the possibility of practical antimicrobial therapy in rheumatology, and in all of medicine. At the same time in a number of clinical situations still retain their significance proven considerably less expensive antibacterial agents. The latter include Doxycycline monohydrate.
Doxycycline monohydrate - a semisynthetic antibiotic of the tetracycline group - was founded in 1967 and over the years is widely used in clinical practice.
According to the chemical structure, it is a 6-deoxy-5-oxytetracycline, and has a mechanism of action common to all tetracyclines. When clinically achievable concentrations, it acts bacteriostatic, disrupting protein synthesis in the microbial cell by binding to the 30 S - subunit of the ribosome RNA.
Compared with tetracycline Doxycycline monohydrate has several advantages pharmacokinetic. Greater degree of absorption from the gastrointestinal tract, and less influence on the food and dairy process; longer half-life (which allows you to assign the drug 1-2 times a day); good penetration in various tissues due to its lipophilicity; lack of accumulation of drug in the blood as a result of increasing its excretion in the feces and increase metabolism with impaired renal function, which allows its use in patients with renal insufficiency.
Due to its special pharmacokinetic properties Doxycycline monohydrate it is much easier to bear than tetracycline. More rare side effects while taking "JUnidoks Soljutab". Neutral reaction to doxycycline monohydrate eliminates esophagitis encountered in the application of other forms of doxycycline.
Therefore, a good combination of chemical formula (monohydrate) and dosage form (tablets Soljutab soluble) makes the drug most secure and treated with the help of most compliance.
Doxycycline hyclate 100mg, like other tetracyclines, is a broad-spectrum antibiotic, however, during long-term use, many bacteria have acquired resistance thereto
In particular, drug-resistant strains over 50% of S. pyogenes, Enterococci majority Many gonococci. It is highly resistant to the drug, and most strains of E. coli, Salmonella, Shigella, enterobacteria.
Based on the above, Doxycycline hyclate 100mg is not used in the A-streptococcal tonsillitis, urinary tract infections, gonorrhea, and others. At the same time it retains its importance as a preparation of the 1st series in many infections and a number can be used situations as an alternative means.
In the last few years it has shown that Doxycycline hyclate 100mg, like other tetracyclines, and other inherent properties that allow to talk about expanding the indications for these drugs, particularly when the RE.
Doxycycline tablets is widely used in the treatment of diseases, sexually transmitted diseases, as one of the most important factors in these diseases is Chlamydia trachomatis
According to the Center for Disease Control (CDC), in 1999 in the US incidence of chlamydial infection was 254 cases per 100,000 population. The most common chlamydial infections found in young women aged 15-24 years.
The share of this pathogen accounts for 30-50% of cases of NGU, much less as the etiological factors appear U. urealyticum and M. genitalium (10-20%). According to the CDC recommendations, for the treatment of patients with acute NGU used doxycycline 100 mg orally twice a day for 7 days or 1 g azithromycin once inside.
According to numerous studies, the efficacy of both circuits is approximately the same, but the cost of treatment with azithromycin is significantly higher than with doxycycline tablets.
A significant part of chlamydial infections are asymptomatic, especially in women, and can lead to infertility and pelvic inflammatory disease. In these cases, as with non-gonococcal urethritis, doxycycline tablets and azithromycin are first-line drugs.
It should be remembered that Doxycycline 100mg, like other tetracyclines, can not be given to children up to 8 years, as these drugs may cause bone growth retardation, tooth discoloration, enamel hypoplasia. Taking into account the possibility of penetration of tetracyclines cross the placenta and breast milk, they are contraindicated in pregnancy and lactation.
Doxycycline tablets are used in combination with other antibiotics (ampicillin / sulbactam, ciprofloxacin, metronidazole) for the treatment of inflammatory diseases of the pelvic organs, as well as in patients with syphilis intolerance b-lactam antibiotics.
Given the sensitivity of the major respiratory pathogen to doxycycline tablets, the drug retains its value in the empirical treatment of infectious exacerbations of chronic bronchitis, as well as not requiring hospitalization community-acquired pneumonia, especially among young people.
With proven chlamydial or mycoplasmal etiology of community-acquired pneumonia doxycycline, along with macrolides, it is used as a first-line agent.
Lyme borreliosis and doxycycline hyclate 100mg
In recent years, the increasing interest of medical professionals, including rheumatologists, attracts Lyme borreliosis (BL) - natural focal infectious disease caused by the spirochete Borrelia genus and transmitted by ticks.
First came to the attention in 1975 when a local outbreak of arthritis in Lyme (USA) BL is now seen as a multisystem disease that affects not only the musculoskeletal system, but also the skin, nervous system, heart, liver, eyes and others. After penetration of Borrelia in the skin at the site of tick suction appears erythema, having a centrifugal growth (tick erythema migrans - LME), which reflects the early stage of the disease.
In the subsequent dissemination of the pathogen can occur from the primary focus of the skin to the various organs and its persistence in the tissues (stage late manifestations).
Typical for BL rheumatic manifestations (arthritis, arthralgia, tendonitis, myositis, enthesopathies, fibrositis) develops after dissemination of the causal agent in the target organs.
Neurologic manifestations of BC presented symptoms, indicating the defeat of both the central (meningitis, encephalitis, myelitis, encephalopathy) and the peripheral nervous system (cranial neuropathy, radiculopathy, and others.). The most common symptoms of heart disease, developing over 3-12 weeks from the onset of the disease are atrioventricular block of varying degrees of severity (from the first to the full).
It has been shown that early (ie, appointed on the LME) antibiotic therapy reduces the risk of secondary erythema, lesions of the joints and blood vessels and, therefore, is an important factor in the further favorable course BL.
The high degree of correlation between the treatment initiated within the first month of illness and recovery. Thus, at PB forecast clearly correlates not only with the optimal antibiotic therapy, but also with its start timing earlier.
With respect to this means of Rheumatology that timely appropriate treatment of local skin infection in fact is the primary prevention of development of arthritis, and other systemic manifestations BL.
In accordance with the recommendations of the American Society of infectious diseases, the first-line drugs for the treatment of early (local and disseminated) phase BL are doxycycline hyclate (100 mg twice a day orally) or amoxicillin (500 mg three times a day orally), appointed during the 14th -21 days.
According to prospective studies, these drugs have demonstrated similar efficacy in the treatment of LME and associated symptoms BL without neurological symptoms and / or atrioventricular block III degree. Cefuroxime axetil, close to the effectiveness of doxycycline in the treatment of CME, referred to as alternative drugs for these patients because of the high cost.
Of particular interest is made in Russia, randomized comparative study 11 treatment regimens in a large group of patients with the LME. Significantly better results obtained with doxycycline (0.2 grams per day per os for 14 days) compared with penicillin (2,000,000. ED day intramuscularly for 10-14 days) and tetracycline (1.2 g per day for 14 days).
Use of cefuroxime in a dose of 1 g per day gave results similar to those of the treatment with doxycycline hyclate 100mg. The best result of treatment is marked with the use of antibiotics in the first 5 days of illness, and the duration of the course of antibiotic therapy is not less than 14 days.
With the development of Lyme arthritis, according to the American recommendations, shows the assignment of doxycycline hyclate 100mg or amoxicillin in the above doses for 28 days.
If, after a course of treatment develop recurrent arthritis, it is advisable the appointment of another antibiotic for oral administration or use of ceftriaxone for 2-4 weeks (not earlier than after 3-4 months. By the end of the previous course of antibiotic therapy).
Certain One noteworthy results of the special epidemiological experiment conducted in Russia on a large group of patients. High efficiency of short-term antibiotic therapy for indications of rapid diagnosis of Borrelia in the tick gut, as a way of preventing tick-borne borreliosis.
Use of doxycycline to 0.2 g per day orally for 3-5 days after the tick bite reduced incidence of 11-fold.
Doxycycline - basic antirheumatic?
For rheumatologists interest to antibiotics is not limited to their direct antimicrobial activity. Not less attention should be given anti-inflammatory and immunomodulatory effects, which, as it turned out during the numerous experimental and clinical studies, has a number of anti-microbial and anti-parasitic agents. These include drugs, and tetracycline group.
Currently, there are enough strong evidence indicating the appropriateness of tetracyclines including doxycycline as a basis in the treatment of RA, particularly rheumatoid arthritis and osteoarthritis.
One of the factors responsible for anti-inflammatory activity of tetracyclines, is the ability of these drugs to inhibit matrix metalloproteinases - specific zinc-dependent enzymes (collagenase, gelatinases, stromelysins, etc.), Play an important role in the degradation of macromolecules of the extracellular matrix of connective tissue.
It is believed that patients with rheumatoid arthritis and osteoarthritis have a local imbalance between the production of the activated forms of metalloproteinases and their tissue inhibitors.
In the literature there are reports on the successful use of doxycycline in patients with rheumatologic profile. The use of this drug in a dose of 150 mg / day for 3 months. in patients with rheumatoid arthritis resulted in a clear positive trend for a number of indicators (joint account, the intensity of pain as determined by a visual analog scale, reduction of collagenase activity in the saliva, various psychopathological parameters).
During a 6-month pilot study that included 23 patients with rheumatoid arthritis, the effectiveness of doxycycline has been comparable to that of methotrexate in the treatment. These results deserve serious attention and clearly indicate the prospects of work in this direction.
On the other hand, is a proven fact the inhibition of matrix metalloproteinases and marked increase in the penetration of doxycycline in the cartilage, subchondral bone and synovial membrane layer in the presence of flurbiprofen led to the conclusion of the feasibility of conducting clinical trials in osteoarthritis doxycycline alleged terms of treatment from 12 to 18 months.
Thus, doxycycline is still one of the most interesting and promising antibiotics. Further application of this preparation, in all probability, will expand the range of indications for his purpose in rheumatology and in other areas of clinical medicine.