Paracetamol is an antipyretic pain reliever

Quite often, during infectious diseases, a person’s body temperature rises. At the same time, in addition to the main drugs, antipyretics are often used in treatment. One of the effective medications that help with hyperthermia is Paracetamol. In addition, this drug is used to relieve various types of pain.

Paracetamol Welfarm

Indications for use

Paracetamol is a drug with antipyretic and analgesic effects. It is prescribed to adults and children for colds and viral diseases, as well as for various types of pain. The main active ingredient of this drug helps block cyclooxygenase in the central nervous system, effectively affects pain receptors and thermoregulation. The medication does not have anti-inflammatory properties and does not have a harmful effect on the mucous membrane of the stomach and intestines, which is why it is successfully used in patients with gastrointestinal diseases. But the drug can have a negative effect on the liver and kidneys, so if the patient has chronic diseases of these organs, then he should use paracetamol with caution.

Features of use by pregnant women

Pregnant women often complain of toothache. Most often, the cause is caries, which appears due to the fact that calcium in a woman’s body is directed to a greater extent towards the structure of the bone tissue of the unborn baby. This causes various problems, particularly with teeth.

Paracetamol is allowed to be taken by pregnant women, but precautions should be taken. The active substance can penetrate the placenta. The minimum dose of the medicine can be taken in the 2nd trimester, when the child’s organs are already formed.

Before taking it, you should consult your doctor. You can drink no more than 1 tablet per day. Repeated use may cause harm to the fetus.

Instructions for use

Paracetamol is prescribed in the following cases:

1. As an antipyretic for infectious and inflammatory diseases that are accompanied by an increase in temperature. In this case, the drug affects the thermoregulation center in the cerebral cortex, resulting in a decrease in body temperature.
2. As an analgesic for various types of pain of mild and moderate severity: headaches, non-inflammatory toothaches, colds, early stages of migraines, acute respiratory infections, muscle pain.
3. Painful menstruation in women (algomenorrhea).
4. Pain from burns and injuries.

How to take Paracetamol?

The dosage of the drug and the course of treatment are determined by the doctor. It all depends on the individual characteristics of the patient, the presence of chronic diseases, the intensity of the pain syndrome, and contraindications. The drug is prescribed orally with a small amount of water, 1 tablet. 2 times a day. To reduce the temperature, it can be used for no more than 3 days. For pain relief, the drug is used for no more than 5 days.

How to take for headaches

The medicine is quite effective for headaches. But when taking it, it is worth considering some features. The tablets should not be taken on an empty stomach. Before taking the pill, you need to have at least something to eat. If there is no appetite, then you can drink a glass of water.

You need to take the tablet with plain water. It is not recommended to use coffee and tea, as the effect may be reduced to zero. If unbearable pain is felt, then you can take 1000 mg of the drug at a time. You can take the medicine again after at least 4 hours. You can take no more than 4 tablets per day. This regimen does not apply to pregnant women (the dosage should be 2 times less).

Paracetamol is prescribed for migraines, which are characterized by persistent, throbbing pain, usually in one part of the head.

If the headache is associated with stress or a nervous condition, then 1 tablet is enough.

Paracetamol for children

It is used to reduce temperature, relieve pain of various localizations; in children, in addition to these indications, the drug is used to reduce the body’s reaction after vaccination.

Children's Paracetamol is available in the form of syrup. Oral dosage for children:

• 6-12 years - 250-500 mg,
• 1-5 years - 120-250 mg,
• from 3 months to 1 year - 60-120 mg,
• up to 3 months - 10 mg/kg.

The interval between doses of the drug is 4 hours, but no more than 3-4 times a day. It is allowed to combine Paracetamol with other antipyretics.

Paracetamol for a child from 3 months

Video “Paracetamol - instructions for use, side effects and method of use”

In the article we will talk about taking paracetamol for joint pain - features of use for arthrosis of the joints, dosage depending on the age group of the patient and the form of release of the medicine. We will indicate contraindications for use, provide a list of possible side effects, compatibility with other drugs, as well as a list of alternative analogues.

Paracetamol is often used for moderate joint pain. The drug has an antipyretic and analgesic effect.

Content

Show contentsIUse of paracetamol as an analgesic for joint painIIParacetamol in the treatment of arthrosisIIIForm of the drugIVHow to take paracetamol for joint pain: dosageVInstructions for use: contraindications and side effectsVICompatibility with other drugsVIIDrug analoguesVIIIConclusion

Tablets for children

Paracetamol in tablet form is prescribed to children over 12 years of age and adults to reduce body temperature.

Paracetamol tablets are used in the following cases:

• increased temperature due to respiratory and other infectious diseases,
• headache,
• toothache,
• neuralgia,
• muscle pain,
• pain from injuries, burns
• painful menstruation in women.

Paracetamol can be used in pregnant women and mothers who are breastfeeding.

How to take for toothache

Often toothache catches a person at the most inopportune moment. Not in all cases it is possible to go to the dentist right away. To eliminate unbearable pain and improve the condition, you can take Paracetamol.

The drug is able to stop the production of prostaglandins, which are the source of pain. The tooth stops hurting, but the inflammatory process continues to spread. If the toothache does not go away, then you should not hesitate to go to the dentist.

You need to take the medicine after meals. Relief is observed after about 15-20 minutes. You can take the pill again no earlier than after 4 hours. You can take 4 tablets per day. Paracetamol can be taken for no more than 3 days.

Syrup for children

The syrup is used in children aged from one month. The drug has an antipyretic and analgesic effect.

Paracetamol is indicated for:

• Pain syndrome of weak and moderate intensity.
• Increased temperature due to respiratory and other infectious diseases.
• Hyperthermia after vaccination.

Dosage of the drug

• To reduce the reaction to vaccination in children, it is recommended to take 2.5 ml of the drug once.
• Children from 3 months to 1 year use 2.5-5 ml of paracetamol.
• For children from 1 to 6 years old, 5-10 ml of the drug is recommended.
• Children from 6 to 14 years old - 10-20 ml of paracetamol.

Most often, the frequency of administration is from 1 to 4 times a day, the interval between doses is 4-5 hours. In addition, it is allowed to take paracetamol simultaneously with other antipyretic drugs.

Drug therapy for pain in patients with arthritis

The modern possibilities of drug treatment of pain in patients with rheumatoid arthritis and osteoarthritis are considered. Particular attention is paid to the place of non-steroidal anti-inflammatory drugs, in particular meloxicam, in the arsenal of rheumatologists, internists, family doctors and doctors of other specialties when managing such patients. The concept of the golden mean in relation to this drug is substantiated. The principles of drug therapy for neuropathic pain in joint pathology are presented.

Table 1. Comparative characteristics of the main groups of NSAIDs used for rheumatoid arthritis

Table 2. Recommendations for the use of NSAIDs for osteoarthritis

Introduction

Chronic pain is one of the main manifestations of arthritis - osteoarthritis, or osteoarthritis (OA), and rheumatoid arthritis (RA). The generally accepted criterion for chronic pain is that it persists for at least three months. However, in a significant proportion of patients with OA and RA, chronic pain syndrome fits the definition of severe (high impact). This is defined as constant pain with significant limitation of the possibility of professional activity, social activity and self-care for six months or more [1].

Chronic pain is a complex and multifactorial phenomenon [2]. The most typical type of arthritis is chronic musculoskeletal pain [3], which is a nociceptive type of pain (occurs due to stimulation of peripheral pain receptors due to damage/inflammation of the affected tissue). However, a significant number of patients develop neuropathic pain associated with damage to the somatosensory nervous system [4].

Treatment of nociceptive pain

Rheumatoid arthritis

Pain is one of the most challenging symptoms in patients with RA.

Pain in RA has traditionally been considered a consequence of inflammation in the joints. However, the results of recent studies indicate that several mechanisms are involved in its development. The following facts confirm this. Pain may begin even before the onset of RA symptoms, and its severity often does not correlate with the degree of inflammation or pharmacological suppression of disease activity [5]. The causes of pain may vary at different stages (early or late) of RA and depend on the presence of exacerbations, as well as on the individual characteristics of the patients. Pain may persist even in the absence of exacerbations [6, 7]. It can intensify with increasing joint damage secondary to the inflammatory process. Moreover, the prevalence of chronic non-inflammatory pain syndromes, such as fibromyalgia, is higher among patients with RA than in the general population [8, 9].

According to the results of the international study QUEST-RA (7028 patients with RA, 83 centers in 30 countries, including Russia) [10], pain is the most important determinant of the patient’s overall assessment of the condition. According to Norwegian researchers, in 30% of patients with RA, taken under observation in the early stages of the disease, for ten years, despite active anti-inflammatory and immunosuppressive treatment, the severity of pain remained quite high (> 40 mm on the visual analogue scale (VAS)) [eleven].

As mentioned above, the mechanism of pain in arthritis is predominantly local (nociceptive). Many inflammatory mediators (bradykinin, histamine, adenosine triphosphate, neurotrophins and cytokines), as well as damaged molecular structures, activate sensory neurons to generate action potentials and/or enhance neuronal excitability and sensory transduction through neuronal receptors. This leads to pain and hyperalgesia. The contribution of cytokines to the initiation of pain is confirmed by the fact that it weakens when cytokines are neutralized or cytokine receptors are blocked at the site of inflammation [12].

It has been established that the inflamed synovium generates mediators such as prostaglandins, bradykinin and pro-inflammatory cytokines (tumor necrosis factor (TNF) alpha, interleukins (IL) 1 and 6, nerve growth factor beta). They sensitize peripheral nerves and thus contribute to the onset and maintenance of pain [13–16]. It should be noted that in addition to the synovium, sensory nerves are localized in the area of ​​the joint capsule, ligaments, external areas of the menisci, subchondral bone, tendon sheaths and muscles [13]. They can also become a source of pain impulses.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of many pain conditions, including rheumatic diseases, because they have antipyretic, anti-inflammatory and analgesic effects [17]. Unlike basic anti-inflammatory drugs, NSAIDs have an analgesic effect, and their therapeutic effect develops quickly. That is why drugs of this group are the basis of symptomatic (pain-relieving) therapy for RA. Thus, this is the main group of drugs for controlling pain in RA in Russia [18] and the USA [19].

The vast majority of NSAIDs do not differ in effectiveness [20]. At the same time, it has been established that NSAIDs may differ in their safety profiles in relation to the gastrointestinal tract (GIT), cardiovascular system, kidneys and liver [21].

The main pharmacological effects of NSAIDs are associated with inhibition of cyclooxygenase (COX) 2 activity [22]. This enzyme is responsible for the production of inflammatory mediators - prostaglandins. Activation of COX-2 leads to the development of pain, including the central mechanisms of pain impulse transmission, inflammatory response, neoangiogenesis, etc. [23]. Another isoform of the enzyme, COX-1, plays an important role in maintaining many parameters of homeostasis, including the protective potential of the gastrointestinal mucosa, renal blood flow, and the process of platelet aggregation. The use of NSAIDs is associated with a natural risk of developing undesirable reactions - erosive and ulcerative lesions of the gastrointestinal tract, bleeding, impaired renal function, destabilization of blood pressure, and thrombotic complications. Depending on the ability of NSAIDs to inhibit the activity of COX-2 or COX-1 in greater or lesser concentrations, they are divided into different groups. Inhibition of predominantly COX-1 is characteristic of acetylsalicylic acid. Thus, to suppress COX-1, a significantly lower concentration of acetylsalicylic acid is required than to suppress COX-2. Therefore, to implement the antiplatelet effect, a dose tens of times less is required than to implement the anti-inflammatory effect. Most NSAIDs are non-selective COX inhibitors. They are able to inhibit the activity of both isoforms at similar concentrations (ibuprofen, indomethacin, naproxen, piroxicam, diclofenac, etc.). The use of non-selective NSAIDs is associated with a fairly high risk of developing adverse reactions from the gastrointestinal tract [24]. Within this group, moderately selective COX-2 inhibitors are often identified, for which the concentrations required to suppress the activity of this isoform are many times lower than the concentrations required to inhibit COX-1 [25]. This group includes meloxicam (Artrosan®), nimesulide and etodolac. More selective for COX-2 are drugs from the coxib group – celecoxib and etoricoxib [26]. The use of selective and moderately selective COX-2 inhibitors is associated with a significantly lower risk of developing adverse reactions from the gastrointestinal tract.

Due to the high selectivity of coxibs for COX-2, there were initially concerns about an increased risk of cardiovascular complications. Indeed, suppression of COX-2 (without affecting COX-1) may lead to an imbalance in the synthesis of thromboxane A2 and prostacyclin and, therefore, increase the risk of vascular thrombosis. In patients with cardiovascular comorbidity, this is fraught with an increased risk of developing myocardial infarction and ischemic stroke [27, 28].

The results of meta-analyses also confirm an increase in cardiovascular risk during treatment with coxibs [29]. In addition, in 2004–2005. Rofecoxib and valdecoxib were withdrawn from the pharmaceutical market, mainly due to the development of cardiovascular accidents [30, 31]. Subsequently, it was shown that other NSAIDs, to varying degrees, can increase cardiovascular risks [32–36].

The drug meloxicam, one of the first COX-2-selective NSAIDs, has a good balance between gastrointestinal and cardiovascular safety.

Meloxicam is a non-steroidal anti-inflammatory drug from the oxicam group. Its half-life is approximately 20 hours. As a result, the possibility of application once a day. Neither moderate renal nor hepatic impairment significantly alters the pharmacokinetics of meloxicam.

In addition, elderly patients do not require dose adjustment of the drug [37].

Meloxicam, along with nimesulide, is a moderately selective COX-2 inhibitor. The ratio of drug concentrations required to suppress the activity of COX-1 and COX-2 ranges from 2.0 to 6.1, when measured by different methods [38–40].

The widespread use of meloxicam began in 1995. The clinical characteristics of meloxicam (the drug Artrosan®) include pronounced analgesic and anti-inflammatory activity.

The drug has been tested for RA. Already by the beginning of the 2000s. Based on the results of meta-analyses of randomized clinical trials, it became obvious that meloxicam is not inferior in effectiveness to non-selective NSAIDs with a significantly better safety profile [41, 42]. Thus, according to the results of a randomized clinical trial that included 894 patients with RA in the acute phase [43], meloxicam in different doses (up to 22.5 mg/day) demonstrated sufficient safety with efficacy comparable to diclofenac at a dose of 150 mg/day.

It should be noted that meloxicam has one of the most favorable safety profiles. In addition, it is one of the most economically acceptable drugs [44, 45].

Another advantage of meloxicam is the availability of different dosage forms, including injection (for intramuscular administration).

Local and general tolerability of meloxicam and piroxicam administered intramuscularly was compared in a multicenter randomized clinical trial [46] in patients with RA (n = 95) or OA (n = 116). The drugs were administered for seven days. Local tolerability of meloxicam was significantly better than that of piroxicam. We are talking, in particular, about such indicators as redness after the first injection (p = 0.03) and global assessment after the first and final injections (p

Another important aspect when choosing NSAIDs is taking into account possible drug interactions. This primarily applies to methotrexate, since NSAIDs can theoretically delay its elimination. It was found that meloxicam did not affect the pharmacokinetics of methotrexate [47].

In addition, meloxicam did not increase the risk of latent hepato- and nephrotoxicity when combined with methotrexate [48]. At the same time, according to the results of a Cochrane meta-analysis, there are certain risks with respect to the combined use of methotrexate, celecoxib and etoricoxib, especially anti-inflammatory doses of acetylsalicylic acid [49]. Thus, for etoricoxib, when taken simultaneously with methotrexate, the development of a severe toxic-allergic complication (Stevens-Johnson syndrome) was recorded [50]. Data have been obtained on adverse drug interactions between methotrexate and non-selective NSAIDs (ketoprofen, indomethacin, naproxen, diclofenac, ibuprofen) [51, 52]. The NSAIDs listed above compete with or inhibit (particularly etoricoxib) the organic anion transporter (hOAT3), which slows the elimination of methotrexate and therefore increases the risk of toxicity [51].

Table 1 summarizes the above facts [28, 53].

Osteoarthritis

The high prevalence of pain in the geriatric population [54] makes a significant contribution to the general therapeutic problem of chronic pain. Long-term analgesia in elderly patients is a complex and poorly understood issue. Elderly people are often not included in randomized clinical trials, so there is limited data in the literature regarding this population. In addition, such patients often have several comorbidities, including cardiovascular diseases. As a result, the risk of drug interactions increases and the range of therapeutic options is limited [54]. This primarily applies to NSAIDs. It should be noted that, along with simple analgesics (paracetamol), NSAIDs are most often prescribed for OA [55, 56].

Indications for the use of NSAIDs for OA according to the recommendations of various medical societies are presented in Table. 2 [55, 57–64]. Thus, NSAIDs should be used systemically as second-line drugs if simple analgesics (paracetamol) or topically (gels, ointments, patches) are insufficiently effective. However, in real practice [65], due to the limited ability to control pain with paracetamol, NSAIDs are often prescribed as first-line therapy.

Another important issue related to NSAIDs is their use without taking into account relative contraindications [66]. Therefore, their use is often associated with significant safety problems.

When prescribing NSAIDs, it is necessary to minimize the risk of adverse reactions, especially in elderly patients. In this regard, there is increasing interest in the use of meloxicam, one of the first moderately selective COX-2 inhibitors, for OA. Meloxicam has confirmed its high effectiveness in OA, including in low doses [67].

In studies in OA [41, 68–70], meloxicam 7.5 and 15.0 mg/day demonstrated efficacy, safety and good tolerability. It was superior to placebo and was comparable to diclofenac 100 mg/day, piroxicam 20 mg/day, and naproxen 750–1000 mg/day for all primary and secondary endpoints. At the same time, the frequency of adverse reactions from the gastrointestinal tract with its use was lower than with the use of diclofenac.

Compared with traditional NSAIDs, meloxicam was less likely to cause dyspepsia. In addition, it was associated with a lower rate of treatment discontinuation due to gastrointestinal complications [71].

The good tolerability of meloxicam is confirmed by the results of a network meta-analysis of 36 randomized clinical trials (n = 112,351). Its authors compared the incidence of gastrointestinal complications when using coxibs and moderately selective NSAIDs - meloxicam, nabumetone and etodolac. In general, the risk of serious complications with meloxicam treatment was lower than with non-selective NSAIDs [37, 72, 73].

Subjective assessment of NSAID tolerability significantly affects the quality of life and often becomes the reason for interruption of therapy, especially in elderly patients. In real practice, meloxicam, along with other COX-2 inhibitors, has demonstrated an undoubted advantage in this regard over most non-selective NSAIDs [74, 75]. Thus, in a German observational study, 13,307 patients received meloxicam 7.5–15.0 mg/day [76]. Indications for the use of NSAIDs were OA (61%), rheumatoid arthritis (24%), ankylosing spondylitis (1.6%) and other rheumatic pathologies (28%). A significant proportion of patients had a high risk of developing adverse reactions: 12% had a history of perforation, ulceration and bleeding in the gastrointestinal tract, 24% had at least one concomitant cardiovascular disorder, and 26% were on antihypertensive therapy. Before meloxicam, many (58%) patients were taking NSAIDs. In 43% of them, previous therapy was not effective enough, and in 21%, adverse reactions occurred due to NSAIDs. In 85 and 94% of patients, respectively, the effectiveness and tolerability of meloxicam therapy were assessed as good or very good. Quality of life and functioning in daily life improved in 64 and 84% of patients. Only 0.8% of patients reported gastrointestinal adverse reactions: four cases of gastric ulceration, one of a serious perforated gastric ulcer, and one of a serious small bowel complication following misuse or overdose of meloxicam. Thus, although patients were at high risk of side effects, treatment safety was good.

The safety of meloxicam in relation to the cardiovascular system has also been sufficiently confirmed. The results of a large population-based study conducted in Finland (33,309 episodes of acute myocardial infarction, controls included 138,949 individuals without this pathology) indicated that the risk of cardiovascular accidents while taking meloxicam was no higher than when using nimesulide, nabumetone and etodolac , coxibs and non-selective NSAIDs [77]. Direct and indirect comparisons with coxibs demonstrated a definite advantage for meloxicam. According to the results of a meta-analysis, which included a large number of randomized clinical trials [44], moderately selective COX-2 inhibitors (meloxicam, etodolac) were significantly superior to non-selective NSAIDs (diclofenac, piroxicam, etc.) in the incidence of adverse events from the gastrointestinal tract with similar effectiveness and absence increasing the risk of developing adverse events from the cardiovascular system. Highly selective COX-2 inhibitors (rofecoxib, celecoxib, etoricoxib) were also significantly safer than non-selective NSAIDs in relation to the gastrointestinal tract, but were associated with an increased risk of myocardial infarction.

A comparative real-life study showed a lower incidence of gastrointestinal and higher incidence of thromboembolic complications during treatment with rofecoxib compared with meloxicam therapy [78, 79].

Meloxicam is also characterized by minimal hepatotoxicity [80]. In randomized clinical trials, meloxicam, celecoxib, and etoricoxib were significantly less likely to cause increases in alanine aminotransferase and aspartate aminotransferase levels than non-selective NSAIDs [81, 82].

According to the results of an analysis of the US Drug Induced Liver Injury Network database, which is a prospective registry of severe idiosyncratic drug-induced hepatotoxicity [83], of 1322 cases of drug-induced hepatotoxicity, only 30 were associated with NSAIDs, the majority (53%) of them with diclofenac. With regard to meloxicam, only three cases of probable hepatotoxicity of the cholestasis type were recorded with a favorable outcome.

In a recently published meta-analysis [84], none of the 18 selected studies reported hepatotoxicity of meloxicam. Eight studies reported hepatotoxicity among three NSAIDs: celecoxib, etoricoxib and diclofenac.

The results of Russian studies confirm the data of international observations. The multicenter PRINCIPLE study, the results of which were published not long ago [85], demonstrated that in real practice meloxicam in relation to indicators such as pain severity and patient satisfaction with treatment, treatment safety, the incidence of adverse reactions (dyspepsia, peripheral edema and increased blood pressure), comparable to celecoxib, nimesulide, aceclofenac and naproxen. However, the incidence of dyspepsia with meloxicam was significantly lower than with diclofenac. According to data from the Republic of Crimea, the number of adverse reactions associated with treatment with meloxicam was lower than when taking diclofenac, ibuprofen, acetylsalicylic acid, ketorolac, metamizole, paracetamol, nimesulide [86].

Thus, the advantages of prescribing moderately selective COX-2 inhibitors (of which meloxicam is a representative) for OA are obvious, primarily for elderly patients.

In connection with the above, it is necessary to recall the concept of the golden mean [28], which is based on the optimal balance of fairly high safety of the drug in relation to both the gastrointestinal tract and the cardiovascular system. This concept is universal and has been discussed in relation to various drugs [22].

An additional benefit of meloxicam as a first-line treatment for OA is its potential beneficial effect on cartilage. It was found that in OA, meloxicam and aceclofenac in concentrations found in synovial fluid had a positive effect on the overall metabolism of proteoglycans and hyaluronic acid in cartilage. Therefore, these two drugs should not interfere with the biomechanical properties of joint tissues and may prevent the progression of OA [87]. The experiment showed that meloxicam, as well as naproxen, are able to suppress the activity of metalloproteinases in the synovial tissue of joints, thereby exerting an organoprotective effect on cartilage tissue [88, 89]. Although this effect appears to apply to different anti-inflammatory drugs.

Meloxicam at both low and high doses had chondroprotective effects in animal models of osteoarthritis. Its high doses have been associated with protection of subchondral bone from damage [90].

Therapy for neuropathic pain

Neuropathic pain occurs in approximately 7% of the population [91]. It can be caused by a number of diseases, injuries, and surgical interventions that lead to disruption of somatosensory pathways in the peripheral or central nervous system [92].

Rheumatic diseases, in particular RA and OA, occupy an important place among the causes of neuropathic pain.

The high prevalence of neuropathic pain in rheumatic diseases is associated with chronic inflammation. During a chronic inflammatory process, the threshold of excitability of neurons in the pain system changes—peripheral and central sensitization. During the inflammatory reaction, the intercellular space in the area of ​​damage is filled with pro-inflammatory mediators, such as TNF-alpha, IL-1, IL-6, prostaglandins, as well as neurotropic factors (nerve growth factor beta, serotonin, substance P, neurokinin A, etc.) [93]. In this case, first, pain receptors are sensitized (become more sensitive) to mechanical or chemical irritation, then they become multimodal (acquire the ability to be excited by any external stimuli), so-called silent nociceptors are activated, turning on only after stimulation by pro-inflammatory mediators [94, 95]. As a result, primary hyperalgesia develops (weak painful stimuli are perceived as strong and prolonged), secondary hyperalgesia, which involves intact tissue, and allodynia (the sensation of pain when exposed to non-painful stimuli) [93].

In OA, the neuropathic component of pain manifests itself as local symptoms in the form of paresthesia (burning, numbness) and the development of hyperalgesia [96–98]. This activates the brain structures responsible for the perception of pain as a manifestation of central sensitization [99, 100].

Even more neuropathic pain is characteristic of RA. Thus, according to the results of a domestic study, using a questionnaire for diagnosing the type of pain (Douleur Neuropathique 4 questions - DN4), pain was found in 43% of RA patients [101].

In RA, the mechanisms of inflammation-induced peripheral and central sensitization also include:

• sensitization of nociceptive neurons with the inclusion of a mechanism of direct action of autoantibodies (in particular, anti-citrullinated antibodies) on the membrane structures of nociceptors of nerve cells, not associated with the inflammatory reaction [93, 102];
• development of direct immunoinflammatory damage to the nervous system in the form of sensorimotor polyneuropathy, mononeuropathy [101];
• mechanical damage to peripheral nerves during tunnel syndromes, the spinal cord (cervical myelopathy with damage to the atlantoaxial joint and other structures of the cervical spine) [101, 103].

In rheumatic diseases, therapy for neuropathic pain should be included in the complex of measures for the treatment of musculoskeletal pain in cases where it is chronic and the mechanism of central sensitization is involved in its pathogenesis [104]. As a rule, NSAIDs are included in this complex. It is known that NSAIDs can influence the central mechanisms of pain formation, since one of the most important mechanisms is determined by the production and accumulation of pro-inflammatory mediators in the tissue of the central nervous system, among which prostaglandin E2 plays a leading role [105].

The importance of this component of therapy is proven by the effectiveness of NSAIDs in direct damage to the peripheral nervous system - radiculopathies. Thus, meloxicam is highly effective not only against spinal radicular syndrome [106], especially in injection form [107–109], but also in preventing its complications [110].

Currently, the following pharmacological treatments are recommended for neuropathic pain [111, 112]:

• first line - anticonvulsants (gabapentin and pregabalin), antidepressants (tricyclic antidepressants and dual serotonin and norepinephrine reuptake inhibitors);
• second line - opioid analgesics and tramadol;
• third line - some antiepileptic drugs, N-methyl-D-aspartate receptor antagonists, capsaicin, etc.

Invasive techniques such as neuromuscular blocks, spinal cord stimulation, intrathecal anesthetics and neurosurgical interventions are also widely used for neuropathic pain [113]. These types of treatment require separate consideration and therefore remain outside the scope of this review.

For neuropathic pain, the effectiveness of non-pharmacological, non-invasive methods such as transcutaneous electrical nerve stimulation and cognitive behavioral therapy has not been well studied and their role remains unclear [113].

A special place in the treatment of neuropathic pain is given to anticonvulsants.

Recently, gabapentin (Convalis®) has occupied an increasingly important place in the treatment of pain in rheumatic diseases. Gabapentin is an anticonvulsant for the treatment of epilepsy as well as neuropathic pain. Gabapentin is structurally similar to the neurotransmitter gamma-aminobutyric acid (GABA), but its mechanism of action is not associated with a direct effect on GABA receptors. It has been established that gabapentin binds to the alpha-2-delta subunit of voltage-gated calcium channels and thus inhibits the flow of calcium ions, which play an important role in the occurrence of neuropathic pain. At clinically relevant concentrations, gabapentin does not bind to other common drug and neurotransmitter receptors found in the brain, including GABAA and GABAB. The use of gabapentin leads to suppression of the release of monoamine neurotransmitters [114].

According to the recommendations of experts from the European Federation of Neurological Societies [115], the group for the study of neuropathic pain at the International Association for the Study of Pain [116], the British National Institute for Health and Clinical Excellence [117], as well as the Russian Expert Society [118], gabapentin is the first drug lines for the treatment of neuropathic pain.

In addition to its proven effectiveness, gabapentin has a good safety profile and the absence of adverse drug interactions [114]. It can be prescribed in combination with most NSAIDs, including meloxicam [119].

B vitamins are traditionally prescribed as an additive therapy method that enhances the effect of basic drugs for neuropathic pain [120]. The active combination of such vitamins is Combilipen® (in injection form) and Combilipen® tabs (in tablet form). These drugs include pyridoxine, thiamine/benfotiamine, and cyanocobalamin in therapeutic doses [121]. The first component provides synaptic transmission and analgesic effect, participating in the synthesis of key neurotransmitters: norepinephrine, dopamine, GABA, serotonin, and is involved in the transport of the nerve sheath component - sphingosine. The second two components stimulate the regeneration of nerve tissue, providing axonal transport, and participate in the conduction of nerve impulses. And finally, the third component, cyanocobalamin, is involved in the synthesis of the myelin sheath of the nerve and has a direct analgesic effect.

These drugs are indicated for complex therapy of mono- and polyneuropathies of various origins, dorsalgia, lumboischialgia, plexopathy, radicular syndrome caused by degenerative changes in the spine.

The experiment demonstrated the potentiating effect of a combination of B vitamins when administered together with NSAIDs [122]. The combined use of meloxicam (the drug Artrosan®) and Combilipen® in patients with low back pain was characterized by a pronounced decrease in the intensity of the pain syndrome, a reduction in the time for its relief, good tolerability, and a low frequency of clinically significant unwanted side effects [123]. Moreover, the positive effect persisted even after the end of the course of therapy.

The effectiveness of Combilipen® tabs in combination with Convalis has been proven for neuropathic pain in patients with diabetic neuropathy [124]. Thus, the administration of a B complex of vitamins was accompanied by a significant decrease in the severity of neuropathic pain.

Conclusion

Pain in rheumatic diseases such as rheumatoid arthritis and osteoarthritis is determined by a combination of nociceptive and neuropathic pain.

NSAIDs are the mainstay of treatment for musculoskeletal pain in arthritis. For most patients, based on the optimal combination of gastrointestinal and cardiovascular safety profiles, moderately selective NSAIDs (meloxicam) may be the drugs of choice.

For neuropathic pain in rheumatoid arthritis and osteoarthritis, it is advisable to prescribe a combination of NSAIDs and anticonvulsants (meloxicam and gabapentin). As an additional agent that potentiates the effect of the main drugs, a complex of thiamine, pyridoxine and cyanocobalamin (the drug Combilipen®) can be considered.

special instructions

When Paracetamol is used simultaneously with certain medications, the harmful effects on the liver increase. For this purpose, it is not recommended to prescribe together such groups of substances as ethanol, sleeping pills, antidepressants, the antibiotic rifampicin - when interacting with Paracetamol, the drugs increase the level of liver enzymes, which negatively affects the organ. Important! The required dosage and duration of the course should be determined by the attending physician. Interaction with alcohol. Paracetamol should not be combined with alcoholic beverages. In addition, the instructions for the drug indicate that persons prone to frequent alcohol consumption should not take this drug. In people who abuse such drinks, liver cells are replaced by connective tissue, which leads to the development of fatty hepatosis or cirrhosis.

In this case, toxic damage to the liver occurs, which manifests itself as follows:

• General weakness, nausea and vomiting appear.
• The patient feels pain in the right hypochondrium, his condition worsens.
• Yellowing of the skin and sclera is noted, confusion and convulsions may occur.

When taking the drug for a long time, it is recommended to monitor the condition of the liver and blood tests.

What is it used for?

If you have joint pain, you should not immediately rush to the pharmacy to buy up the entire source of healing available to the pharmacist. First, you need to contrast all the pros and cons of the medicine, study the method of its use, storage, analogues, contraindications. These properties of paracetamol will be discussed in this article.

Paracetamol (20 rubles)

So, the medicine is known to us as an inexpensive antipyretic and analgesic drug, which is marketed on the pharmaceutical market in the form of tablets and suppositories. Indicated for use by adults, children, including infants. Here it is important to correctly calculate the amount of the drug so as not to harm the patient.

Tablets, syrup, capsules, suppositories are used as one of the medications in complex therapy. For example, for joint disease, the medicine is taken by combining it with Diclofenac. This effect on the inflamed area of ​​the human musculoskeletal system enhances the effect of application and relieves pain faster. Before starting treatment, be sure to talk to a qualified healthcare professional about how to take paracetamol if you have joint pain.

The medicine is taken to lower body temperature, eliminate general weakness, increased fatigue or reduce headaches. Sometimes pediatricians recommend a pharmacological drug for young children when teething or inflammation of the child’s oral cavity. Interestingly, the inexpensive drug gets rid of pimples, as well as acne.

Interaction with other drugs

When using Paracetamol, interactions with other drugs should be taken into account.

• When this drug is used simultaneously with inducers of microsomal liver enzymes, the risk of liver damage increases, so their combined use is not permissible.
• When used together with drugs that affect hematopoiesis, an increase in some indicators (prothrombin time) is possible.
• When the drug is used simultaneously with anticholinergics, the effect of the former is reduced.
• When taken together with oral contraceptives, the analgesic effect of paracetamol is reduced.
• When used simultaneously with uricosuric drugs, their effectiveness decreases.
• When using sorbents (activated carbon) with the drug paracetamol, the effect of the latter is reduced.
• When this medicine is combined simultaneously with the drug zidovudine, a negative effect on hematopoiesis and the liver is possible.
• When used simultaneously with carbamazepine, phenytoin, phenobarbital, primidone, the effectiveness of paracetamol is reduced, since the latter affects metabolic processes in the body.
• When the drug paracetamol is used together with anticonvulsants (lamotrigine), the removal of the latter from the body is accelerated.
• When used simultaneously with certain drugs (rifampicin, sulfinpyrazone), the metabolism of paracetamol in the liver increases.
• The simultaneous use of the drug paracetamol with antiviral drugs (for example, arbidol, kagocel) is acceptable.
• Concomitant use with broad-spectrum antibiotics (for example, amoxiclav) is permitted.

Storage and analogues

There are many drugs that are considered analogues of paracetamol. They can only be prescribed by a doctor, who is guided by the reasons for the prescription, the reaction of the individual organism to the active substances, the presence of contraindications for use, etc.

The most famous analogues of paracetamol are:

1. Panadol. The drug consists of paracetamol and caffeine, the ratio of which is designed to relieve inflammation, relieve pain, and normalize body temperature. It is marketed as tablets and is recommended for use only by children over 12 years of age or by adults. At the same time, a person should consume no more than four grams per day.
2. Baralgetas. Analgin and pitofeton act on the source of inflammation in a similar way to paracetamol. It can be used in the absence of contraindications for children or adults. It is only important to correctly calculate the number of active ingredients, depending on the weight and age of the patient.
3. Nimid. The basis of the pharmacological agent is nimesulide. This medicine actively fights inflammation in the joints, normalizes body temperature, and relieves pain. Typically used as tablets, granules or suspensions.

The drug with a good shelf life should be stored in a clean, dry place with limited exposure to sunlight. The temperature where the drug is stored should in no case exceed 25 degrees (depending on the form of release). Such conditions are optimal for storing paracetamol for two to three years.

Manufacturers of an effective medicine that fights various types of inflammation or fever require compliance with the storage standards indicated on the packaging. At the same time, remember that paracetamol, like any other medicine, should be stored in a place where it is difficult for a small child to reach on his own.

Contraindications

Like any medicine, paracetamol has some contraindications.

Paracetamol Extratab

It is not recommended to use Paracetamol in these cases:

• if you are hypersensitive to paracetamol,
• elderly people over 65 years old,
• children under two years old,
• if a person has liver and kidney diseases,
• for blood diseases (for example, hemophilia).

Use with caution

• jaundice (Gilbert's syndrome),
• congenital increase in blood bilirubin.

Before taking the drug, you should definitely consult your doctor if:

• if you have severe liver or kidney disease,
• you are taking drugs against nausea and vomiting (metoclopramide, domperidone), as well as drugs that lower blood cholesterol (atorvastatin),
• you are taking anticoagulants and need painkillers every day for a long time. In this case, paracetamol can be taken occasionally.

Diagnostics

Diagnosing rheumatoid arthritis in the early stages can be difficult. Unfortunately, there is no pathognomic analysis that allows a confident diagnosis of rheumatoid arthritis. But nowadays, the diagnosis of rheumatoid arthritis is based on factors closely associated with this disease. There are a number of criteria for diagnosing rheumatoid arthritis:

• Morning stiffness in and around joints for at least one hour.
• Simultaneous swelling in three or more joints
• The presence of swelling in the wrist or fingers.
• Symmetrical involvement of similar joints on both sides.
• Rheumatoid nodules are tumor-like formations in the skin (mainly in the elbow area).
• The presence of an increased level of rheumatic factor in the blood.
• X-ray signs of changes in the hands and wrists with damage to the bone tissue around the joints characteristic of rheumatoid arthritis.

The diagnosis of rheumatoid arthritis can be reliably made if 4 or more factors are present. The first four factors must be present for at least 6 weeks. The doctor needs to see the joints when the process is activated due to the following reasons:

• Patients cannot always describe their symptoms.
• Rheumatoid arthritis may present like other joint diseases
• Patients sometimes do not pay attention to mild pain and endure it until it is time to seek medical help.
• Some diseases that mask rheumatoid arthritis can make it difficult to diagnose: - gout, fibromyalgia, other autoimmune diseases (for example, SLE).

In view of the above, early diagnosis can be difficult. In fact, the average time from the onset of symptoms to diagnosis is almost 9 months.

Although diagnosing rheumatoid arthritis is not an easy task, it is extremely important to correctly identify the disease. A late diagnosis can be fraught with consequences due to the early involvement of internal organs in the process. Experts believe that timely treatment allows for good long-term results.

The doctor needs to carry out a number of measures in order to make a diagnosis:

• Medical history It is important to provide your doctor with information about the frequency, intensity, and time of day when symptoms occur.
• Physical examination The examination allows you to visually assess the presence of an inflammatory process in the joints.
• Laboratory tests These include both general tests and detection of rheumatic factor and high levels of sialic acid or the presence of autoantibodies, changes in the level of various enzymes, etc.
• Radiography allows you to diagnose any damage to bone tissue.

Side effects of the drug Paracetamol

Like any medicine, paracetamol has a number of side effects. Infrequent adverse reactions that may occur after using paracetamol include:

• Hives;
• Skin itching;
• Rash;
• Quincke's edema.

Rare adverse reactions include:

• On the part of digestion: nausea, vomiting, abdominal pain are possible.
• From the side of hematopoiesis - anemia, thrombocytopenia, leukocytopenia.

If adverse reactions occur, stop taking the medication and the doctor selects another drug.

Effect of the drug

Paracetamol has been considered a popular and sought after pain reliever and antipyretic for half a century. Efficiency is associated with uniform distribution across tissues.

The active ingredients block the action of prostaglandins, which are sources of pain. This eliminates moderate pain. The drug also copes well with fever. This serious symptom can indicate a variety of infectious and inflammatory diseases.

Before taking it, you should consult your doctor and read the instructions to prevent side effects. You should strictly follow the dosage, otherwise complications related to the functioning of the heart and kidneys may occur. The risk increases when taken concomitantly with alcoholic beverages.

Signs of poisoning do not appear immediately. Initially, your general well-being may only slightly deteriorate.

Pharmacodynamics

The drug belongs to the group of non-narcotic analgesics - the drug has an analgesic effect. Paracetamol has a pronounced antipyretic and analgesic effect. The biochemical basis of these reactions is inhibition of cyclooxygenase (one of the leading enzymes responsible for the synthesis of prostaglandins - mediators of inflammation).

Thus, the synthesis of prostaglandins is inhibited in the nervous system, which, moreover, have a pyrogenic effect (leading to an increase in temperature) on the hypothalamus, where the thermoregulation center is located. The hypothalamus is a brain structure responsible for both maintaining the required body temperature and producing certain hormonal factors. Inhibition of prostaglandin synthesis leads to a decrease in their pyrogenic effect on the hypothalamus, heat transfer from the body increases, and temperature decreases.

In parallel, Paracetamol affects the conduction of pain sensitivity impulses along afferent nerve fibers. This mechanism of action provides an analgesic effect.

Research is being conducted on the effect of Paracetamol on the serotonin system, as well as cannabinoid transmission in the brain.

Pregnancy and lactation

The use of Paracetamol during pregnancy is justified if the potential benefit to the mother outweighs the risk to the health of the fetus. During the period of active breastfeeding, the mother is not prohibited from taking Paracetamol. It has been proven that the medicinal compound passes into breast milk in very small quantities, which does not affect the baby’s health. In addition, published data regarding the use of Paracetamol during lactation indicate that breastfeeding is not a contraindication for taking the drug.