Quick drugs for the treatment of osteoarthritis

Non-narcotic analgesics (for example, paracetamol) are more often used during the washing period when NSAIDs are approved. However, the results of comparative studies conducted in the 80-90s of the last century indicate that paracetamol may be an alternative to other NSAIDs whose analgesic and anti-inflammatory effect is indisputable as a symptomatic therapy for osteoarthritis in patients with mild to moderate pain syndrome .

[1], [2], [3], [4], [5], [6], [7]

Paracetamol

The mechanism of action of paracetamol is associated with a decrease in the activity of oxidized forms of cyclooxygenase (COX) -1 and -2 in the CNS and spinal cord.

The main clinical symptom of osteoarthritis is pain - weakly correlated with the histological changes of the synovial membrane and articular cartilage. In addition, the pain in osteoarthritis can be caused not only by synovitis, but also by stretching of the joint capsule, ligaments, as well as nerve endings in the period above the OB, trabecula microperforations, intraosseous hypertension, muscle spasm. Based on the foregoing, we can conclude that with osteoarthritis, there is not always a need for an anti-inflammatory effect of the symptomatic agent.

The results of comparative studies of the efficacy and tolerability of NSAIDs in patients with osteoarthritis in the vast majority of cases demonstrate a moderate positive dynamics of the joint syndrome. Thus, for example, patients treated with VCH Tyson and A. Glynne (1980), before treatment with ibuprofen or benoxaprofen, noted sensible pain per 100 mm of VAS at an average of 55 mm, and after 4 weeks of treatment, at 34 mm, i.e., the dynamics was only 21%. In other studies, it was noted that the dynamics of indices of the joint syndrome fluctuated between 10-20% against the background of NSAID treatment and a similar difference (ie, 10-20%) was recorded between the results in the main group and in the placebo group. Usually patients with osteoarthritis per 100 mm of VAS mark the initial value of pain at the level of 40-60 mm, which against the background of course therapy NSAIDs decreases to 25-45 mm. Therefore, it is not surprising that "simple" analgesics in many patients are no less effective than NSAIDs.

Paracetamol treatment of patients with knee osteoarthritis of varying severity was found to be effective in 30% of them, including patients taking before NSAIDs.

JD Bradley and co-authors (1991) compared the efficacy of paracetamol and ibuprofen in a double-blind, placebo-controlled study in patients with manifest gonarthrosis with moderate joint changes on radiographs. The authors found that the effectiveness of the "anti-inflammatory" dose of ibuprofen (2,400 mg / day) did not differ from the "analgesic" dose of ibuprofen (1200 mg / day), and paracetamol at a dose of 4000 mg / day. In addition, in patients with clinical signs of synovitis (swelling, effusion), the dynamics of the studied parameters under the influence of the "anti-inflammatory" dose of ibuprofen did not differ from that in the treatment with paracetamol. Similar results were obtained by J. Stamp et al. (1989) who compared the efficacy and tolerability of paracetamol and flurbiprofen in patients with osteoarthritis.

JH Williams and co-authors (1993) conducted a two-year, double-blind, placebo-controlled comparative study of paracetamol efficacy at a dose of 0.65 g 4 times a day and naproxen 375 mg twice daily. Of the 178 randomized patients, only 62 completed the study, and in the paracetamol-taking group, the number of out-patients was slightly higher than that in the group treated with naproxen. A high percentage of informed consent for participation in the study is likely due to suboptimal doses of both drugs studied. In terms of efficacy and tolerability, paracetamol and naproxen did not differ.

A comparative study of the effectiveness of paracetamol in a dose of 3 g / day, as well as combinations of paracetamol in a dose of 3 g / day and codeine - 180 mg / day was interrupted, despite the noted more pronounced analgesic effect. The cause of premature termination of the study was a high incidence of side effects in patients taking paracetamol / codeine.

According to P. Seidemann and co-authors (1993), the analgesic effect was more pronounced when naproxen was added to paracetamol (4 g / day) at a dose of 0.5 or 1 g / day, this combination being as effective as naproxen alone at a dose of 1 , 5 g / day. Despite. That these data require confirmation, they indicate the advisability of combining paracetamol in a therapeutic dose with naproxen in a low dose.

According to KD Brandt (2000), in 40-50% of patients with osteoarthrosis, effective control of joint pain can be achieved with paracetamol, but it is not possible to predict the analgesic effect of simple analgesics in a particular patient.

The main advantage of paracetamol in comparison with other NSAIDs is a lower toxicity in relation to the digestive tract. However, an overdose of the drug (above 10 g / day) is associated with hepatotoxicity. In a population-based study in Sweden, it was found that the hospitalization rate associated with hepatotoxicity of paracetamol was 2 per 100,000 population per year. In patients with liver disease, the phenomenon of hepatotoxicity is observed with the use of paracetamol in usual therapeutic doses (up to 4 g / day). The results of clinical observations indicate that in patients with chronic alcoholism, hepatotoxicity occurs when paracetamol is treated with a dose of <10 g / day. To avoid side effects, it is necessary to prescribe paracetamol in the minimal dose, which allows to achieve a therapeutic effect, and also not recommend it to people who are sick with alcoholism.

Paracetamol does not inhibit the synthesis of prostaglandins in the epithelium of the kidneys, but in the experiment its tropism is shown to the kidneys of the kidneys with excessive accumulation of its metabolites in the papilla tissue, which is associated with the development of paracetamol-specific papillary necrosis. Data from the literature indicate the development of side effects on the part of the kidneys with an overdose of paracetamol. TG Murray and co-authors (1983) found no connection between chronic renal insufficiency (CRF) and analgesics. TV Perneger and co-authors (1994) reported on the results of a study of the risk of developing chronic renal failure when taking OTC analgesics. According to their data, the cumulative dose of paracetamol over 1000 tablets doubles the risk of developing chronic renal failure. At the same time, the authors of the study argue that these results indicate a lack of connection between the intake of acetylsalicylic acid and the development of chronic renal failure. The data of T. V. Perneger and co-authors are questionable and require confirmation. The National Kidney Foundation recommends paracetamol as an analgesic drug of choice in patients with impaired renal function.

At the same time, the results of the study of SM. Fored and co-authors (2001) of the materials of the Swedish Population Register for 1996-1998. Showed that regular use of paracetamol, acetylsalicylic acid, or both drugs increases the risk of developing chronic renal failure. The authors emphasize that previous kidney diseases or systemic pathology are predisposing factors. 926 patients with the first established diagnosis of renal insufficiency and 998 controls were examined, of which 918 and 980 respectively had the necessary documentation. Among patients with renal insufficiency, acetylsalicylic acid and paracetamol were regularly taken at 37 and 25%, respectively, and in the control group - 19 and 12%. The relative risk of developing kidney failure increased with the duration of admission and the increased dose of drugs that was more consistent in paracetamol than acetylsalicylic acid, but the authors could not exclude the role of predisposing factors.

Paracetamol does not affect the function of platelets, so it can be recommended as a drug of choice for patients with osteoarthritis taking anticoagulants.

Paracetamol is able to prolong the half-life of warfarin mainly in patients taking the latter at a dose above 10 mg / day. Therefore, patients taking warfarin with paracetamol should carefully monitor the prothrombin time.

Narcotic analgesics are not recommended for patients with osteoarthritis. Because of the high risk of side effects (nausea, vomiting, constipation, urinary retention, confusion, drowsiness, mental and physical dependence, etc.) opium derivatives for osteoarthritis are used only in special clinical situations.

Tramadol

Tramadol is a relatively new analgesic, is a synthetic opioid, has two mechanisms of action:

• interacts with the c-opioid receptors,
• oppresses the seizure of norepinephrine and serotonin.

As an anesthetic, tramadol in a dose of 100 mg is more effective than codeine in a dose of 60 mg and is comparable with the combinations of codeine with acetylsalicylic acid or paracetamol. In a two-week comparative study of the use of tramadol (300 mg / day) and dextropropoxyphen (300 mg / day) in 264 patients with osteoarthritis, 70% of patients with tramadol and 50% of dextropropoxyphene showed a decrease in pain in the affected joints. However, the former caused more side effects (mainly nausea / vomiting, dizziness). According to a double-blind randomized comparative study of the efficacy of tramadol (300 mg / day) and diclofenac (150 mg / day) in 60 patients with osteoarthritis, at the end of the 1st and 4th weeks of treatment, the pain reduction in the affected joints was similar in both groups; this study also reports a greater number of side effects in treatment with tramadol (23 cases) compared with diclofenac (2 cases). SF Roth (1995) published the results of a placebo-controlled study of tramadol in 50 patients with osteoarthritis who have pain syndrome on the background of NSAIDs. Treatment with tramadol was more effective than placebo, but was accompanied by a large number of side effects, mainly the appearance of nausea, constipation, drowsiness.

When administering tramadol in recommended doses, severe side effects (respiratory depression) are not fixed. To reduce the risk of dyspepsia, it is advisable to titrate the dose of tramadol to the target for 4-5 days, starting at 50 mg / day, D. Choquette and co-authors (1999) recommend the appointment of tramadol to patients with osteoarthritis only in case of ineffectiveness or intolerance of NSAIDs and paracetamol.

Codeine and dextropropoxyphene

Codeine and dextropropoxyphen are representatives of synthetic opioids, which are often used in the treatment of osteoarthritis in combination with NSAIDs and / or paracetamol, despite the ability to induce dependence. In a comparative study, a combination of paracetamol in a dose of 2 g / day and dextropropoxyphen at a dose of 180 mg / day in patients with osteoarthrosis was more effective than paracetamol (3 g / day) and codeine (180 mg / day). Another study found that dextropropoxyphene and paracetamol are better tolerated by patients than dihydrocodeine. However, according to RI Shorr and co-authors (1992), the risk of fracture of the femur in elderly patients receiving codeine or dextropropoxyphen was 1.6 (95% confidence intervals (CI) = 1.4-1.9), and the combination codeine or dextropropoxyphene with psychotropic drugs (sedatives, antidepressants, etc.) increased the risk of fractures to 2.6 (95% DI = 2.0-3.4).

[8], [9], [10]