The most common definition of low back pain (LBP) is the presence of pain localized between the lower border of the 12th pair of ribs and the gluteal folds [1-3]. Back pain is associated with up to 6% of all direct costs for the treatment of various diseases, 15% of days of incapacity for work and 18% of causes of disability, which makes this pathology a medical and social problem [2]. In 8-10% of cases, acute pain syndrome can transform into chronic pain. In our country, patients seek outpatient medical care for back pain in 17–46% of cases [4–6]. According to international studies, 49–70% of surveyed adults from random samples suffered from back pain at least once in their lives [7, 8]. As a rule, in 60% of cases, a few weeks after the onset of LBP, recovery is noted, but in 40% of cases, the recovery period is prolonged and the risk of chronic pain increases [9]. Russian epidemiological studies of pain syndromes show a high prevalence of chronic back pain, which is about 56.7% [2, 6]. The highest frequency of chronic pain is typical for women, people with low incomes and elderly patients, and it is also associated with psycho-emotional disorders and has cultural and ethnic characteristics. People of working age (35–55 years) suffer from LBP to a greater extent, although they often occur in other age groups, including adolescence [2].
The etiology of primary LBP syndrome is considered to be musculo-ligamentous dysfunction, musculoskeletal disorders, spondylosis, less commonly protrusion, intervertebral disc herniation, etc. The main causes of secondary LBP are diseases of the internal organs (cardiovascular, genitourinary systems, lungs, gastrointestinal tract and etc.), endocrine and other diseases.
Musculoskeletal (nonspecific) back pain is the most common, its share is up to 70-85% in the structure of pain syndromes. In 27% of cases, there are pain syndromes associated with structural changes in the spine (discoradicular conflict, facet conflict, discogenic pain syndromes, traumatic injuries of the spine). Specific causes of back pain syndromes, which are based on visceral pathology, malignant neoplasms, infectious and inflammatory lesions of the spine, are diagnosed in 3-5% of cases [1, 3, 10, 11].
The pathogenesis of acute pain is usually due to nociceptive afferentation. Neuropathic pain is associated with damage to the structures of the peripheral nervous system. The causes of the formation of chronic pain syndrome can be peripheral nociceptive effects, as well as dysfunction of the peripheral or central nervous system. The mechanism of development of LBP syndrome is associated with the release into the intercellular fluid of algogenic compounds - inflammatory mediators (bradykinin, prostaglandins, leukotrienes, biogenic amines), which play an important role in the formation of pain syndrome caused by damage, ischemia and inflammation. Efferent stimulation of the sympathetic nervous system has a certain effect on the pathogenesis of LBP, firstly, due to an increase in vascular permeability at the site of damage and an increase in the concentration of inflammatory mediators and, secondly, as a result of the direct effect of sympathetic neurotransmitters (norepinephrine, adrenaline) on α2- adrenoreceptors. During the process of nociceptive stimulation, the release of glutamate and neuropeptides from the central terminals of C-afferents is induced, which leads to the formation of persistent changes in the excitability of nociceptive neurons [2, 12, 13].
In ICD-10, primary nonspecific benign LBP corresponds to code M54.5. Based on the duration, LBP is classified into acute (up to 6 weeks), subacute (6 to 12 weeks) and chronic (more than 12 weeks). A characteristic feature of back pain is a combination of reflex muscular-tonic and myofascial syndromes with changes in the psycho-emotional sphere, against the background of which the condition becomes chronic.
According to modern recommendations, the diagnosis of LBP is aimed primarily at identifying “symptoms of a threat” through a careful collection of complaints and anamnesis and a physical examination of the patient. “Threat symptoms” refer to serious and life-threatening illnesses. If any are identified, an appropriate diagnostic search is carried out using the necessary clinical and instrumental examination. If the presence of any specific pathology is excluded, the patient's back pain is classified as nonspecific. In accordance with international standards, if a patient with back pain does not have “threat symptoms” or radicular pain, there is no need to conduct a laboratory and instrumental examination, including radiography of the spine or computed tomography (CT) and magnetic resonance imaging (MRI) [10— 12]. Often, with the help of modern imaging methods, degenerative-dystrophic changes in the spine are detected even in patients without back pain. For example, MRI of the lumbar spine in people under 40 years of age reveals asymptomatic herniated intervertebral discs in 30-40% of cases, and in people over 60 years of age - in 100% [11]. Diagnosis of LBP is based primarily on clinical methods, since the presence of a degenerative process in the spine cannot be the direct cause of back pain, but is only a prerequisite for its occurrence. A number of studies have found no correlations between the presence of signs of degenerative-dystrophic damage to spinal tissues and the nature and intensity of the pain syndrome in patients with nonspecific LBP. In this regard, many modern domestic and foreign guidelines for diagnosing LBP do not include x-ray examination in the plan for the initial examination of patients [10, 12, 14].
The tactics for managing patients with acute nonspecific LBP includes several basic principles: 1) correctly informing the patient about the causes of the disease, effective treatment methods and the high probability of rapid pain resolution; 2) exclusion of bed rest, which can only slow down the healing process and worsen the prognosis of the disease; 3) avoidance of muscle strain and excessive physical activity; 4) prescription of non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, muscle relaxants; 5) maintaining habitual daily activity while reducing pain, which contributes to a faster and more complete resolution of the pain syndrome and restoration of the patient’s previous functional status [2, 12, 15].
Thus, in addition to the cognitive-behavioral and physical components in the complex of measures aimed at treating LBP, drug therapy with NSAIDs plays a major role in the process of restoring motor functions impaired by back pain, since it is considered pathogenetically justified. Numerous randomized controlled trials have shown that NSAIDs are highly effective for acute back pain. The feasibility of using NSAIDs due to their reliable effectiveness both in acute back pain and in exacerbation of chronic pain without radicular syndrome was convincingly shown in a meta-analysis of 65 controlled studies [16, 17]. The pathogenetic validity of the use of NSAIDs for LBP has been confirmed by a number of studies, during which markers of inflammation were identified in the tissues of the lumbar region in patients with chronic nonspecific back pain - high activity of C-reactive protein, increased levels of interleukin-6 (IL-6) and necrosis factor tumors (TNF) [18]. The mechanism of action of NSAIDs is associated with the suppression of the activity of the enzyme cyclooxygenase (COX), which catalyzes the conversion of free polyunsaturated fatty acids into prostaglandins, as well as other eicosanoids - thromboxanes and prostacyclin. Prostaglandins are inflammatory mediators involved in the process of sensitization of receptors to pain mediators (histamine, bradykinin) and mechanical agents, thereby lowering the pain threshold. In addition, prostaglandins play an important role in providing protection to the mucous membrane of the gastrointestinal tract (GIT). However, the side effects of NSAIDs in the form of the development of undesirable reactions from the gastrointestinal tract, kidneys, liver, blood vessels, and bronchopulmonary system are also associated with inhibition of the synthesis of prostaglandins and eicosanoids [16, 19]. In clinical guidelines for the diagnosis, treatment and prevention of nonspecific LBP, NSAIDs are considered first-line drugs, but attention is drawn to the high frequency of side effects with long-term use of these drugs [1, 10, 12]. According to the recommendations of the European Medicines Agency, NSAIDs should be used in the lowest effective doses, for the shortest possible duration, sufficient to relieve pain [20, 21]. Despite the abundance of NSAIDs on the Russian pharmacological market, none of the representatives of this drug group can be considered ideal in terms of their pharmacological properties. However, the use of NSAIDs includes the widespread use of nimesulide in outpatient neurological practice for the treatment of LBP.
The purpose of the work is a retrospective analysis of the effectiveness and safety of the use of nimesulide (Nemulex) in the treatment of patients with acute LBP syndrome who were treated on an outpatient basis.
Indications for use of Nimesulide
What are the pills for? Indications for use of Nimesulide are:
- osteoarthritis;
- rheumatoid arthritis;
- bursitis;
- tendinitis;
- arthritis of various origins.
The drug is prescribed for the relief of acute pain in myalgia , algodismenorrhea , toothache, arthralgia , headache , and in the postoperative period.
The drug has no effect on the progression of the disease, and is effectively used to reduce the severity of the inflammatory process, to reduce pain, and also as symptomatic therapy.
Contraindications
Nimesulide is not prescribed for erosive and ulcerative diseases of the digestive tract, for bronchial asthma , intolerance to drugs of the NSAID group, for cerebrovascular and other bleeding, for ulcerative colitis , inflammatory bowel diseases, hemophilia , Crohn's disease, recurrent form of polyposis of the paranasal sinuses and nose, for active bleeding in the gastrointestinal tract, with blood clotting disorders .
The drug is not used in case of progressive pathology of the renal system, with a severe form of renal failure, with hepatotoxic reactions due to a history of use of nimesulide, with active diseases of the hepatic system, with a decompensated form of chronic heart failure , during pregnancy , with hyperkalemia , children under 12 years, with the simultaneous use of other gapatotoxic drugs, in the period after coronary artery bypass grafting .
Side effects
The use of the drug Nimesulide can cause a number of side effects.
Central nervous system: Reye's syndrome , headache, nightmares, fear, anxiety, dizziness, nervousness.
Skin: increased sweating, itching, rashes, dermatitis , erythema, angioedema , toxic epidermal necrolysis, erythema multiforme exudative, urticaria , Stevens-Johnson syndrome.
Urinary system: interstitial nephritis , renal failure, hematuria, dysuria , urinary retention, oliguria .
Digestive tract: cholestasis, gastritis, flatulence , constipation, increased levels of liver enzymes, bleeding from the gastrointestinal tract, vomiting, nausea, diarrhea, jaundice, fulminant hepatitis , pain in the epigastric region, perforation and ulcerative lesions of the stomach walls.
Hematopoietic organs: increased bleeding time, hemorrhage , purpura, pancytopenia, thrombocytopenia, anemia.
Respiratory system: bronchospasm , shortness of breath, possible exacerbation of existing bronchial asthma.
Sense organs: visual disturbances in the form of blurred vision.
Cardiovascular system: “flushes” of blood flow to the skin of the face, a drop in blood pressure, rapid heartbeat. Hypothermia , general weakness, and increased levels of potassium ions are also noted
Nimesulide in the treatment of chronic joint diseases
Joint diseases of various locations are one of the most common reasons for visiting a doctor, along with arterial hypertension. Joint diseases are socially significant diseases.
First, these diseases affect a large part of the population. The most common joint disease is osteoarthritis (OA), especially in people over 65 years of age, when its prevalence reaches 97% of the population. Among chronic inflammatory diseases of the joints, the most common is rheumatoid arthritis (RA), a disease that almost obligately leads to disability in patients within 3–5 years from the onset of the disease.
Secondly, these diseases characterize the development of persistent pain, which can be associated with various causes. The most common cause of pain in joint pathology is the development of synovitis. However, in OA, the development of pain may be associated with other pathogenetic components of the disease. Normally, all joint structures have pain endings, with the exception of cartilage. But with OA, partial vascularization and innervation of the cartilage occurs. Thinning and damage to the cartilage reduces its shock-absorbing properties, and the load on the subchondral bone increases with the development of swelling and pain. In addition, cartilage fibrillation also induces pain and inflammation.
Data obtained from studying the effect of pain on the prognosis of OA indicate:
- About 20% of patients do not receive adequate treatment for chronic pain syndrome, so their pain level on a 10-cm visual analogue scale (VAS) is 5 cm or more [1].
- Chronic pain due to OA leads to a decrease in women's life expectancy by an average of 10–12 years.
- The life expectancy of elderly patients with OA depends to a greater extent on the intensity of pain than on the presence of concomitant potentially life-threatening diseases [2].
- The risk of OA progression is as much associated with pain as with radiographic changes.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic, anti-inflammatory and antipyretic effects. Therefore, they are indispensable in the treatment of arthrological diseases. The rapid development of the analgesic effect determines the obligatory nature of their use in the treatment of joint pathology. The positive therapeutic effect of NSAIDs is associated with inhibition of COX-2. This enzyme, participating in the breakdown cascade of cell membranes damaged during inflammation and other lesions, is responsible for the release of pro-inflammatory prostaglandins and other inflammatory mediators not only in the joints, but also in other organs and tissues, primarily in the walls of blood vessels. Based on the above, it becomes clear that the use of selective COX-2 inhibitors has important clinical and social significance.
In clinical practice, selective COX-2 inhibitors have taken a strong place, although the full potential of their capabilities is still not used by practitioners. “Myths” often arise about their potential toxicity, primarily in relation to the cardiovascular system. Information on the hepatotoxicity of nimesulides has been published in the Western literature, based on isolated and poorly documented clinical cases. I would like to specifically discuss these aspects in this message, taking the drug “Nise” as an example.
The drug "Nise" is a selective inhibitor of COX-2, which has been proven in in vivo studies [7] and in vitro on molecular models [6]. In addition, the drug has several other important mechanisms of action (Fig.). The greatest experience in using the drug “Nise” in rheumatological practice in the Russian Federation has been accumulated in the treatment of patients with OA. Patients with OA, as a rule, have a high risk of developing gastrointestinal complications due to age, the frequent presence of concomitant vascular, cardiac, and renal pathologies and the need to use concomitant therapy. Nise is usually used by this category of patients at a daily dose of 200 mg/day. This ensures the achievement of a clinical effect in 87% [8] - 93% [9] of patients with good tolerability of Nise in relation to the gastrointestinal tract, both according to domestic data (Table 1) and according to foreign controlled studies, post-marketing studies of tolerability nimesulide in 17 countries in 118,831,385 patients [10–13].
Our study involved 40 patients with OA (32 patients) and RA (8 patients), aged from 49 to 79 years (58.8 ± 18.3 years), suffering from arterial hypertension for more than 5 years, receiving a stable dose of antihypertensive drugs. medications for at least 6 months, without obvious manifestations of heart failure. Most patients received ACE inhibitors (enalapril 10-30 mg/day) - 28 patients, β-blockers (propranolol 20-40 mg/day) - 12 patients. After a 3-day break from taking NSAIDs (ibuprofen, meloxicam, ketoprofen, diclofenac), all patients were randomly assigned to either diclofenac at a dose of 100–150 mg/day or Nise at a dose of 200–400 mg/day for 20 days. Blood pressure was recorded 6 times a day: after waking up, before the first intake of antihypertensive or nitrate drugs, 2 hours after taking them, and then 3 more times at equal intervals during the entire “washing” period, the first and last week of taking NSAIDs, the rest of the time blood pressure studies were recorded 4 times a day every 3 hours from the moment of awakening. During the study period, patients kept a diary recording their blood pressure, antihypertensive medication use, and adverse reactions. Statistical processing was carried out using the conjugate pair method.
By the end of the “washing” period, almost all patients in both groups showed an increase in average daily blood pressure (Table 2). However, during the 1st week of treatment (Table 2), the differences in mean systolic pressure were significantly greater when taking diclofenac, and when taking Nise, they were practically no different from the baseline (p < 0.001). To a lesser extent, with diclofenac during the 1st week of treatment, the average daily diastolic blood pressure (DBP) increased by 3.31 ± 5.42; an increase in this parameter by the end of the 1st week of treatment with Nise was not recorded. In 16 out of 20 patients receiving diclofenac, a negative effect of the drug on the course of arterial hypertension was noted - an increase in systolic and/or diastolic pressure, accompanied by unpleasant subjective sensations - headache, cardialgia (16), the development of a hypertensive crisis (2 patients - withdrawal of diclofenac after 6 –14 days of admission), increased need for antihypertensive drugs (6 patients). Among patients receiving Nise, there were no cases of increased need for antihypertensive therapy and no significant changes in blood pressure levels, so all 20 patients completed the 3-week treatment period. Diclofenac was discontinued in 8 patients due to a change in the course of arterial hypertension: the development of a hypertensive crisis (2 patients) and an increase in blood pressure levels, both systolic and diastolic (2 patients), which required an increase in the dose of enalapril in both patients; in 2 patients due to gastralgia, in 1 patient due to diarrhea; in 1 patient due to headache. The increase in average daily systolic pressure in patients who completed treatment with diclofenac was statistically significant and amounted to 15.74 ± 11.0; by the end of Nise treatment - 1.71 ± 5.22 (p > 0.05). It is known that changes in systolic blood pressure (SBP) are a more important risk factor for cardiovascular pathology than changes in DBP [19]. Decrease in SBP level by 12 mm Hg. Art. reduces the risk of myocardial infarction by 27%, worsening congestive heart failure by 55%, and stroke by 56% [19, 20].
Similar results were demonstrated in the study by V.I. Mazurov et al. [21], who compared hemodynamic parameters in patients with OA (n = 40), with (23 patients) or without (17 patients) concomitant arterial hypertension (AH), when prescribing Nise or diclofenac for 1 month. Patients of all subgroups were comparable in terms of OA localization and radiological stage. Patients who had OA in combination with hypertension were approximately 10 years older than patients with normal blood pressure levels. The dose of Nise was 200 mg/day and diclofenac 100 mg/day. For the treatment of hypertension, all patients in the second subgroup were prescribed Renitec (enalapril) 5–10 mg 2 times a day. All patients, before the prescription of NSAIDs and after 1 month, in addition to a clinical examination and pain assessment (on the VAS scale), underwent an ECG, 24-hour blood pressure monitoring, impedanceometric cardiography (IMC), and determination of the level of desquamated endothelial cells in the peripheral blood according to the method of Hladovec J. et al. (1978), determination of the state of endothelium-dependent and endothelium-independent (nitroglycerin test) vasodilation (EDVD, ENVD, respectively) of the brachial artery using high-resolution ultrasound.
After one month of treatment, no statistically significant differences in pain reduction according to VAS were noted when taking Nise or diclofenac (p > 0.05). Data on the average parameters of 24-hour blood pressure monitoring are presented in
And
When Nise was prescribed to patients with OA without hypertension (group 1A), the average daily SBP and the average daily SBP and DBP increased within normal values without subjective sensations. In group 1B, who received diclofenac, there was a more significant increase in systolic and DBP, both average and average daily (p < 0.05), which was accompanied by a deterioration in the well-being of patients, and in one case the prescription of antihypertensive therapy was required.
In the group of patients with OA and hypertension who received Nise (2A), no statistically significant increase in blood pressure levels was recorded, but when treated with diclofenac (group 2B), the levels of average daily SBP (p < 0.01), average daily SBP (p < 0 .05), while the SBP area index increased more than 2 times per day (p < 0.05), and DBP increased almost 3 times (p < 0.05), which indicates a stable increase in blood pressure during the day. These changes in blood pressure were accompanied by a deterioration in the well-being of patients, the appearance of shortness of breath, edema of the lower extremities, and correction of antihypertensive therapy was required (increasing the dose of Renitec or using combination therapy).
When studying the parameters of systemic hemodynamics in subgroups of patients receiving Nise, no significant changes were detected. In the subgroup of patients with initially normal blood pressure levels who received diclofenac, there was a significant (p < 0.05) increase in total peripheral resistance (TPSR), a decrease in parameters reflecting the overall performance of the heart: cardiac index (CI) and stroke index (SI), and also a significant increase in the volume of extracellular fluid. Even more significant negative dynamics of systemic hemodynamic parameters were detected in patients with hypertension who received diclofenac. In a comparative study of the effect of Nise and diclofenac on endothelial function in patients with OA with hypertension, it was found that taking Nise did not affect the indicators of EDV and EDV, while treatment with diclofenac resulted in statistically significant (p < 0.05) changes in EDV, EDV and number of desquamated endothelial cells. These data indicate that the non-selective COX inhibitor diclofenac significantly worsened endothelial function, although the mechanisms of this effect remain unclear and require further study.
These data once again confirm that the use of selective COX-2 inhibitors, which include the drug "Nise", has a positive effect on the condition of the vascular endothelium. In patients at risk of developing thrombosis, these drugs should be prescribed together with low doses of Aspirin. This combination can lead to an increase in the incidence of gastrointestinal complications, so these patients should be carefully monitored with endoscopic examination of the gastrointestinal tract and monitoring of hemodynamic parameters, and preventive measures (Table 5).
The drug "Nise" is an effective anti-inflammatory drug. As with all NSAIDs, its effectiveness is dose dependent. When treating patients with OA, as a rule, it is sufficient to prescribe it at a dose of 200 mg/day, which provides both an analgesic and anti-inflammatory effect. As mentioned above, COX-2 inhibitors, unlike classical NSAIDs, do not have a negative effect on articular cartilage. In addition, nimesulide in the spectrum of its mechanism of action includes inhibition of IL-1b [22], inhibition of chondrocyte apoptosis [23], and suppression of metalloprotease activity [24], which confirms the absence of a negative effect on articular cartilage. In chronic inflammatory joint diseases, such as RA or psoriatic arthritis (PsA), the severity of synovitis can be many times greater than in OA, which requires individual selection of a daily dose of Nise from 200 to 400 mg/day. An increase in its effectiveness with increasing daily dose in RA was shown by domestic authors, and in PsA by foreign authors [25].
Thus, the drug “Nise” has proven itself to be an active NSAID; with individual selection of its dose, the number of patient “responders” reaches 93% in combination with good tolerability.
For questions regarding literature, please contact the editor.
N. V. Chichasova , Doctor of Medical Sciences, Professor G. R. Imametdinova E. L. Nasonov , Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Medical Sciences MMA named after. I. M. Sechenova , Moscow
Interaction
The risk of hepatotoxicity increases significantly with the simultaneous use of hepatotoxic medications. The drug increases the effectiveness of anticoagulants. When taking Furosemide, there is a decrease in the severity of its diuretic effect.
Nimesulide displaces salicylic acid, fenofibrate and furosemide from their bonds with proteins. The drug increases the level of lithium ion concentration in the blood plasma.
The drug can increase the toxicity of methotrexate and enhance the nephrotoxic effect of Cyclosporine . The risk of gastrointestinal bleeding increases with simultaneous therapy with selective serotonin reuptake inhibitors and glucocorticosteroids.
NIMESULIDE
special instructions
Since iimesulide is partially eliminated by the kidneys, its dose in patients with impaired renal function should be reduced depending on creatinine clearance.
Considering reports of visual impairment in patients taking other NSAIDs. Treatment should be stopped immediately if any visual disturbance occurs and the patient should be examined by an ophthalmologist.
The drug can cause fluid retention in tissues, so patients with high blood pressure and cardiac disorders should use nimesulide with extreme caution.
Patients should undergo regular medical monitoring if they, along with nimesulide, take medications that are known to affect the gastrointestinal tract. If signs of liver damage appear (itching, yellowing of the skin, nausea, vomiting, abdominal pain, dark urine, increased activity of liver transaminases), you should stop taking the drug and consult your doctor. The drug should not be used simultaneously with other NSAIDs.
During treatment with nimesulide, it is recommended to avoid the simultaneous use of hepatotoxic drugs, analgesics, other NSAIDs (with the exception of low doses of acetylsalicylic acid used in antiplatelet doses) and the use of ethanol does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases and diseases.
The use of the drug may adversely affect female fertility and is not recommended for women planning pregnancy.
After 2 weeks of using the drug, monitoring of biochemical indicators of liver function is necessary.
Gastrointestinal bleeding or ulcer/perforation may develop at any time while using the drug, with or without clinically significant symptoms. both with and without a history of gastrointestinal complications. The risk of their development is higher when high doses of NSAIDs are prescribed, when taken by patients with a history of gastric and duodenal ulcers, as well as by the elderly. If therapy is necessary in these cases, the need for concomitant use of misoprostol or proton pump inhibitors should be considered. If gastrointestinal bleeding or gastrointestinal ulcers occur, the drug should be discontinued.
Elderly patients most often develop side effects when taking the drug, including gastrointestinal bleeding, perforation, dysfunction of the heart, kidneys, and liver, so regular clinical monitoring of the condition of these patients is recommended.
special instructions
During treatment with Nimesulide, patients are recommended to monitor the condition of the liver system twice a month. If the level of liver enzymes increases, itching, rashes, pain in the epigastric region, jaundice, or darkening of the urine appear, treatment is stopped.
Reviews of the drug Nimesulide indicate impaired visual perception in patients who have been taking the drug for a long time. If any changes in the visual organs are registered, therapy is stopped and a mandatory full ophthalmological examination is carried out.
The description of the medication indicates possible fluid retention in the body, which requires caution when treating patients with hypertension .
It is not recommended to prescribe Nimesulide together with other medications from the NSAID group.
The drug cannot replace the preventive effect of antiplatelet agents, despite a pronounced decrease in the rate of platelet aggregation.
The drug is not prescribed to women planning pregnancy due to its negative effect on fertility.
Nimesulide may affect driving.
Results and discussion
Analysis of examination data from the studied group of patients showed that reflex muscular-tonic syndrome - tension and pain on palpation of the paravertebral muscles - was present in all patients. Thus, in 100% of patients, clinical neurological examination revealed signs caused only by muscular-tonic syndrome. When analyzing the results of an X-ray examination of the spine, all patients showed varying degrees of severity of degenerative-dystrophic changes. In order to exclude compression-radicular pathology, 14 (26%) patients underwent CT or MRI of the lumbar spine, which revealed median and/or paramedian localization of disc protrusion of varying severity without compression of the spinal cord roots and signs of spinal canal stenosis. By the 5th day of non-mulex therapy, the severity of spontaneous pain according to VAS, which was 3.86±1.28 points before treatment, and 6.62±1.25 points during movement, was statistically significant ( p
<0.001) decreased, amounting to 1.53±0.34 points at rest, and with movement 2.74±0.67 points.
10 days after the start of treatment, almost complete relief of pain was noted ( p
<0.001): 0.78±0.14 points at rest, and with movement 1.12±0.18 points according to VAS. Along with pain relief, patients with LBP showed improved mobility in the lumbar spine, both flexion when bending forward and lateral mobility when bending to the right and left. Analysis of the results of treatment of patients with LBP depending on gender did not show significant differences between men and women.
No serious adverse events were identified. On the 10th day, one patient had an increase in liver transaminases (maximum 1.5 times higher than normal), which resolved within 1 week with diet. Dyspepsia was recorded in 2 patients, which was relieved by the patients following a diet and taking proton pump inhibitors (omeprazole 40 mg per day) after 1 week. These patients underwent esophagogastroduodenoscopy, which did not reveal serious changes in the gastrointestinal tract. We did not find any significant fluctuations in blood pressure and blood lipid spectrum during the retrospective analysis.
A retrospective analysis of the effectiveness and safety of the use of nimesulide (Nemulex) in the treatment of patients with acute LBP who were treated on an outpatient basis confirmed the information about the high anti-inflammatory activity and safety of nimesulide, previously noted both in multicenter foreign and domestic studies. Reliable data obtained on the relief of pain and increased mobility in the lumbar spine when prescribing Nemex at a dose of 200 mg per day already on the 5th day of treatment indicate the effectiveness of anti-inflammatory therapy in terms of restoring the previous functional status of patients with LBP. The use of non-mex was accompanied not only by a statistically significant analgesic effect (0.78±0.14 points at rest; 1.12±0.18 points when moving according to VAS on the 10th day of treatment), but also by high safety (only in 1 of 54 patients had increased liver transaminases; 2 had dyspepsia without endoscopic changes in the gastrointestinal tract).
The advantage of nimesulides, belonging to the sulfonanilide class, is their relatively low effect on COX-1 in the gastric mucosa, but inhibition of its activity in areas of inflammation. Due to its biochemical properties, nimesulide easily enters inflammation sites, being there in a higher concentration than in plasma. In addition, nimesulide, unlike non-selective NSAIDs, does not affect the production of histamine and, thus, does not contribute to the development of symptoms of “aspirin asthma” [22]. In recent years, it has been shown that this group of drugs not only has a COX-dependent symptomatic effect, but to a certain extent is capable of suppressing immune responses, which is manifested by a decrease in the activity of proinflammatory cytokines. A large number of studies, including those carried out from the standpoint of evidence-based medicine, have shown the high effectiveness of nimesulide for both acute and chronic pain characteristic of LBP. Despite the severity of the analgesic and anti-inflammatory effects of nimesulide, it is well tolerated, which is confirmed by a number of foreign studies [23-25].
However, symptomatic NSAID therapy should be carried out in the shortest possible courses to minimize adverse events. It is necessary to take into account the likelihood of the risk of developing erosive and ulcerative changes in the gastrointestinal tract in patients with a high risk of NSAID gastropathy while taking NSAIDs, therefore it is advisable to use proton pump inhibitors for prophylactic purposes. It should also be taken into account, especially in outpatient practice, that NSAIDs have maximum effectiveness in the early stages of the development of back pain, with acute and subacute pain, and compliance with generally accepted approaches in the management of patients with acute nonspecific LBP in most cases leads to positive treatment results, improvement functional status and prevention of relapses and chronicity of pain.
Nimesulide's analogs
Level 4 ATX code matches:
Nimulid
Diacerein
Aponil
Chondroitin sulfate
Sigan
Don
Nimegesic
Artiflex
Nimesil
Nimika
Artron Hondrex
Artron Flex
Artron Complex
Arthroker
Arthrodarin
Nemulex
Chondroitin
Glucosamine Hydrochloride
Glucosamine
Nimid Forte
Analogues of Nimesulide are the following drugs:
- Ameolin
- Aponil
- Mesulid
- Nise
- Negan
- Nimegesic
- Nimesil
- Nimesin
- Nimid
- Nimujet
- Nimulid
- Nimuspaz
- Remesulide
- Remisid
- Sulidin
Nimesulide price, where to buy
The price of Nimesulide for a package of 20 tablets of 100 mg is 50 - 150 rubles.
- Online pharmacies in RussiaRussia
- Online pharmacies in UkraineUkraine
- Online pharmacies in KazakhstanKazakhstan
ZdravCity
- Nimesulide-Teva tablets 100 mg 30 pcs. Blupharma-Industry Pharmaceuticals
177 rub. order - Nimesulide tab. 100mg 20pcsOzon LLC
125 rub. order
- Nimesulide tablets 100 mg 20 pcs. Ozon LLC
103 rub. order
- Nimesulide tablets 100 mg 20 pcs. Replek Pharm LLC Skopje MK/ JSC BFZ
68 RUR order
- Nimesulide Renewal tab. 100 mg No. 20 Renewal JSC "PFK Obnovleniye" RU
RUB 159 order
Pharmacy Dialogue
- Nimesulide Welfarm (tab. 100 mg No. 30) Welfarm LLC
186 RUR order
- Nimesulide-Teva (tab. 100 mg No. 20)Bluepharma
RUB 139 order
- Nimesulide-Teva (100 mg tablet No. 20)Bluepharma
RUB 154 order
- Nimesulide-Teva tablets 100 mg No. 30Bluepharma
172 RUR order
- Nimesulide-LekT (tab. 100 mg No. 20) Tyumen chemical-pharma plant/Patent-Pharm
61 rub. order
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Pharmacy24
- Nimesulide-Darnitsa 100 mg No. 30 tablets PrAT" Pharmaceutical company "Darnitsa", Ukraine
36 UAH. order - Nimesulide 0.1 g No. 30 tablets PrAT "Lekhim-Kharkiv", Kharkov, Ukraine
37 UAH order
- Nimesulide 100 mg No. 12 tablets PRAT "Fitofarm", Ukraine
13 UAH order
PaniPharmacy
- NIMESULIDE tablets Nimesulide tablets. 100 mg No. 30 Ukraine, Lekhim-Kharkov CJSC
53 UAH order
- Nimesulide tablets Nimesulide tablets. 0.1g No. 30 Ukraine, Lubnyfarm PJSC
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Material and methods
The medical records of 54 patients, 32 women and 22 men aged 32-65 years (average - 46.2±9.1 years) with primary LBP syndrome, were studied. The criteria for inclusion
in the study
were: acute period of LBP, taking non-mex 100 mg 2 times a day after meals in the form of a suspension for 10 days, stopping taking other NSAIDs and muscle relaxants 4 or more days before starting treatment with non-mex, excluding taking psychotropic and other drugs. analgesic agents.
Exclusion criteria
were the presence of spinal injuries and the consequences of spinal surgery in history, compression-radicular syndromes, clinical signs of gastric or duodenal ulcers, kidney disease, blood diseases, hypersensitivity to NSAIDs. The analysis took into account data from a clinical neurological examination, assessment of pain intensity at rest and during movement on a visual analogue scale (VAS), severity of Lasegue's symptom, limitation of movements in the lumbar spine (flexion, lateral mobility to the right and left). The assessment of the patients' condition, the effectiveness and safety of treatment was carried out based on information obtained during three visits (days 1, 5 and 10). The safety of therapy was monitored by taking into account undesirable side effects, analyzing data from physical examination and laboratory monitoring (increased serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin or its fractions). Cardiovascular safety was assessed by blood pressure and blood lipid levels on the 10th day.
The retrospective analysis used medical documentation of patients treated in the neurological department of City Clinic No. 166 of Moscow. Statistical processing was carried out using Microsoft Office Excel 2010 (Microsoft Corp., USA).