The inflammatory process in almost all cases accompanies rheumatic pathology, significantly reducing the patient's quality of life. That is why one of the leading directions in the treatment of joint diseases is anti-inflammatory treatment. Several groups of drugs have this effect: non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids for systemic and local use, in part, only as part of complex treatment, chondroprotectors.
In this article, we will consider the group of drugs listed first - NSAIDs.
Non-steroidal anti-inflammatory drugs (NSAIDs)
This is a group of drugs whose effects are anti-inflammatory, antipyretic and analgesic. The severity of each of them in different drugs is different. These drugs are called non-steroidal because they differ in structure from hormonal drugs, glucocorticoids. The latter also have a powerful anti-inflammatory effect, but at the same time they have the negative properties of steroid hormones.
Mechanism of action of NSAIDs
The mechanism of action of NSAIDs is non-selective or selective inhibition (inhibition) of varieties of the COX enzyme - cyclooxygenase. COX is found in many tissues of our body and is responsible for the production of various biologically active substances: prostaglandins, prostacyclins, thromboxane and others. Prostaglandins, in turn, are mediators of inflammation, and the more of them, the more pronounced the inflammatory process. NSAIDs, inhibiting COX, reduce the level of prostaglandins in tissues, and the inflammatory process regresses.
Scheme of prescription of NSAIDs
Some NSAIDs have a number of fairly serious side effects, while other drugs in this group are not characterized as such. This is due to the peculiarities of the mechanism of action: the effect of drugs on various types of cyclooxygenase - COX-1, COX-2 and COX-3.
COX-1 healthy person found in almost all organs and tissues, in particular, in the digestive tract and kidneys, where it performs its most important functions. For example, prostaglandins synthesized by COX are actively involved in maintaining the integrity of the gastric and intestinal mucosa, maintaining adequate blood flow in it, reducing secretion of hydrochloric acid, increasing the pH, the secretion of phospholipids and mucus, stimulating the proliferation (reproduction) of cells. Drugs that inhibit COX-1 cause a decrease in the level of prostaglandins not only in the focus of inflammation, but throughout the body, which can lead to Negative consequences, which will be discussed below.
COX-2, as a rule, is absent in healthy tissues or is found, but in small quantities. Its level rises directly during inflammation and in its very focus. Drugs that selectively inhibit COX-2, although they are often taken systemically, act specifically on the focus, reducing the inflammatory process in it.
COX-3 is also involved in the development of pain and fever, but it has nothing to do with inflammation. Some NSAIDs affect this particular type of enzyme and have little effect on COX-1 and 2. Some authors, however, believe that COX-3, as an independent isoform of the enzyme, does not exist, and it is a variant of COX-1: these questions need to be conducting additional research.
Classification of NSAIDs
Exists chemical classification non-steroidal anti-inflammatory drugs, based on the structural features of the molecule of the active substance. However a wide range readers, biochemical and pharmacological terms are probably of little interest, so we offer you another classification, which is based on the selectivity of COX inhibition. According to her, all NSAIDs are divided into:
1. Non-selective (affect all types of COX, but mainly COX-1):
- Indomethacin;
- Ketoprofen;
- Piroxicam;
- Aspirin;
- Diclofenac;
- Acyclofenac;
- Naproxen;
- Ibuprofen.
2. Non-selective, affecting equally COX-1 and COX-2:
- Lornoxicam.
3. Selective (inhibit COX-2):
- Meloxicam;
- Nimesulide;
- Etodolac;
- Rofecoxib;
- Celecoxib.
Some of the above drugs have practically no anti-inflammatory effect, but have a greater analgesic (Ketorolac) or antipyretic effect (Aspirin, Ibuprofen), so we will not talk about these drugs in this article. Let's talk about those NSAIDs, the anti-inflammatory effect of which is most pronounced.
Briefly about pharmacokinetics
Non-steroidal anti-inflammatory drugs are used orally or intramuscularly.
When taken orally, they are well absorbed in the digestive tract, their bioavailability is about 70-100%. They are better absorbed in an acidic environment, and a shift in the pH of the stomach to the alkaline side slows down absorption. The maximum concentration of the active substance in the blood is determined 1-2 hours after taking the drug.
When administered intramuscularly, the drug binds to blood proteins by 90-99%, forming functionally active complexes.
They penetrate well into organs and tissues, especially into the focus of inflammation and synovial fluid (located in the joint cavity). NSAIDs are excreted from the body in the urine. The elimination half-life varies widely depending on the drug.
Contraindications to the use of NSAIDs
Preparations of this group are undesirable for use in the following conditions:
- individual hypersensitivity to components;
- , as well as other ulcerative lesions of the digestive tract;
- leuko- and thrombopenia;
- heavy and;
- pregnancy.
Main side effects of NSAIDs
These are:
- ulcerogenic effect (the ability of drugs of this group to provoke the development of the gastrointestinal tract);
- dyspeptic disorders (discomfort in the stomach, and others);
- bronchospasm;
- toxic effects on the kidneys (violation of their function, increased blood pressure, nephropathy);
- toxic effects on the liver (increased activity in the blood of hepatic transaminases);
- toxic effects on the blood (decrease in the number of formed elements up to aplastic anemia, manifested);
- prolongation of pregnancy;
- (skin rash, anaphylaxis).
The number of reports of adverse reactions of drugs of the NSAID group received in 2011-2013 Features of NSAID therapy
Since the drugs of this group, to a greater or lesser extent, have a damaging effect on the gastric mucosa, most of them must be taken without fail after a meal, drinking plenty of water, and, preferably, with the parallel use of drugs to maintain the gastrointestinal tract. As a rule, proton pump inhibitors act in this role: Omeprazole, Rabeprazole and others.
Treatment with NSAIDs should be carried out for the shortest possible time and at the lowest effective doses.
Persons with impaired renal function, as well as elderly patients, as a rule, are prescribed a dose below the average therapeutic dose, since the processes in these categories of patients are slowed down: the active substance both has an effect and is excreted for a longer period.
Consider the individual drugs of the NSAID group in more detail.
Indomethacin (Indomethacin, Metindol)
Release form - tablets, capsules.
It has a pronounced anti-inflammatory, analgesic and antipyretic effect. Inhibits aggregation (sticking together) of platelets. The maximum concentration in the blood is determined 2 hours after ingestion, the half-life is 4-11 hours.
Assign, as a rule, inside 25-50 mg 2-3 times a day.
The side effects listed above are quite pronounced for this drug, therefore, at present it is used relatively rarely, giving way to other, safer drugs in this respect.
Diclofenac (Almiral, Voltaren, Diklak, Dicloberl, Naklofen, Olfen and others)
Release form - tablets, capsules, injection, suppositories, gel.
It has a pronounced anti-inflammatory, analgesic and antipyretic effect. Rapidly and completely absorbed in the gastrointestinal tract. The maximum concentration of the active substance in the blood is reached after 20-60 minutes. Almost 100% absorbed with blood proteins and transported throughout the body. The maximum concentration of the drug in the synovial fluid is determined after 3-4 hours, the half-life of it from it is 3-6 hours, from the blood plasma - 1-2 hours. Excreted in urine, bile and feces.
As a rule, the recommended adult dose of diclofenac is 50-75 mg 2-3 times a day by mouth. The maximum daily dose is 300 mg. The retard form, equal to 100 g of the drug in one tablet (capsule), is taken once a day. With intramuscular injection, a single dose is 75 mg, the frequency of administration is 1-2 times a day. The drug in the form of a gel is applied in a thin layer on the skin in the area of inflammation, the frequency of application is 2-3 times a day.
Etodolak (Etol Fort)
Release form - capsules of 400 mg.
The anti-inflammatory, antipyretic and analgesic properties of this drug are also quite pronounced. It has moderate selectivity - it acts mainly on COX-2 in the focus of inflammation.
Rapidly absorbed from the gastrointestinal tract when taken orally. Bioavailability does not depend on food intake and antacids. The maximum concentration of the active substance in the blood is determined after 60 minutes. 95% binds to blood proteins. The plasma half-life is 7 hours. It is excreted from the body mainly with urine.
It is used for emergency or long-term therapy of rheumatological pathology:, as well as in the case of pain syndrome of any etiology.
It is recommended to take the drug 400 mg 1-3 times a day after meals. If prolonged therapy is necessary, the dose of the drug should be adjusted once every 2-3 weeks.
Contraindications are standard. Side effects are similar to those of other NSAIDs, however, due to the relative selectivity of the drug, they appear less frequently and are less pronounced.
Reduces the effect of some antihypertensive drugs, in particular ACE inhibitors.
Aceclofenac (Aertal, Diclotol, Zerodol)
Available in the form of tablets of 100 mg.
A worthy analogue of diclofenac with a similar anti-inflammatory and analgesic effect.
After oral administration, it is rapidly and almost 100% absorbed by the gastric mucosa. With the simultaneous intake of food, the rate of absorption slows down, but its degree remains the same. It binds to plasma proteins almost completely, spreading throughout the body in this form. The concentration of the drug in the synovial fluid is quite high: it reaches 60% of its concentration in the blood. Middle period elimination half-life is 4-4.5 hours. It is excreted mainly by the kidneys.
Of the side effects, dyspepsia, increased activity of hepatic transaminases, dizziness should be noted: these symptoms are quite common, in 1-10 cases out of 100. Other adverse reactions are much less common, in particular, in less than one patient per 10,000.
It is possible to reduce the likelihood of side effects by prescribing the minimum effective dose to the patient as soon as possible.
It is not recommended to take aceclofenac during pregnancy and lactation.
Reduces the antihypertensive effect of antihypertensive drugs.
Piroxicam (Piroxicam, Fedin-20)
Release form - tablets of 10 mg.
In addition to anti-inflammatory, analgesic and antipyretic effects, it also has an antiplatelet effect.
Well absorbed in the gastrointestinal tract. Simultaneous ingestion of food slows down the rate of absorption, but does not affect the degree of its effect. The maximum concentration in the blood is observed after 3-5 hours. The concentration in the blood is much higher with intramuscular administration of the drug than after taking it orally. 40-50% penetrates into the synovial fluid, found in breast milk. Undergoes a number of changes in the liver. Excreted with urine and feces. The half-life is 24-50 hours.
The analgesic effect is manifested within half an hour after taking the pill and persists for a day.
Dosages of the drug vary depending on the disease and range from 10 to 40 mg per day in one or more doses.
Contraindications and side effects standard.
Tenoxicam (Texamen-L)
Release form - powder for solution for injection.
Apply intramuscularly at 2 ml (20 mg of the drug) per day. In acute - 40 mg 1 time per day for 5 days in a row at the same time.
Enhances the effects of indirect anticoagulants.
Lornoxicam (Xefocam, Larfix, Lorakam)
Release form - tablets of 4 and 8 mg, powder for solution for injection containing 8 mg of the drug.
The recommended oral dose is 8-16 mg per day for 2-3 times. The tablet should be taken before meals with plenty of water.
Intramuscularly or intravenously administered 8 mg at a time. Multiplicity of injections per day: 1-2 times. The solution for injection must be prepared immediately before use. The maximum daily dose is 16 mg.
Elderly patients do not need to reduce the dosage of lornoxicam, however, due to the likelihood of adverse reactions from the gastrointestinal tract, persons with any gastroenterological pathology should take it with caution.
Meloxicam (Movalis, Melbek, Revmoxicam, Recox, Melox and others)
Release form - tablets of 7.5 and 15 mg, injection of 2 ml in an ampoule containing 15 mg of the active substance, rectal suppositories, also containing 7.5 and 15 mg of Meloxicam.
Selective COX-2 inhibitor. Less often than other drugs of the NSAID group, it causes side effects in the form of kidney damage and gastropathy.
As a rule, in the first few days of treatment, the drug is used parenterally. 1-2 ml of the solution is injected deep into the muscle. When the acute inflammatory process subsides a little, the patient is transferred to the tablet form of meloxicam. Inside, it is used regardless of food intake, 7.5 mg 1-2 times a day.
Celecoxib (Celebrex, Revmoxib, Zycel, Flogoxib)
Release form - capsules of 100 and 200 mg of the drug.
A specific COX-2 inhibitor with a pronounced anti-inflammatory and analgesic effect. When used in therapeutic doses, it practically does not have a negative effect on the mucosa of the gastrointestinal tract, since it has a very low degree of affinity for COX-1, therefore, it does not cause a violation of the synthesis of constitutional prostaglandins.
As a rule, celecoxib is taken at a dosage of 100-200 mg per day in 1-2 doses. The maximum daily dose is 400 mg.
Side effects are rare. In the case of long-term use of the drug in a high dosage, ulceration of the mucous membrane of the digestive tract, gastrointestinal bleeding, agranulocytosis and.
Rofecoxib (Denebol)
The release form is a solution for injection in 1 ml ampoules containing 25 mg of the active substance, tablets.
Highly selective COX-2 inhibitor with pronounced anti-inflammatory, analgesic and antipyretic properties. Virtually no effect on the mucous membrane of the gastrointestinal tract and kidney tissue.
Be wary appoint women in the 1st and 2nd trimesters of pregnancy, during lactation, persons suffering or severe.
The risk of developing side effects from the gastrointestinal tract increases when taking high doses of the drug for a long time, as well as in elderly patients.
Etoricoxib (Arcoxia, Exinef)
Release form - tablets of 60 mg, 90 mg and 120 mg.
Selective COX-2 inhibitor. It does not affect the synthesis of gastric prostaglandins, it does not affect the function of platelets.
The drug is taken orally, regardless of the meal. The recommended dose directly depends on the severity of the disease and varies between 30-120 mg per day in 1 dose. Elderly patients do not need to adjust the dosage.
Side effects are extremely rare. As a rule, they are noted by patients taking etoricoxib for 1 year or more (for serious rheumatic diseases). The range of adverse reactions that occur in this case is extremely wide.
Nimesulide (Nimegesic, Nimesil, Nimid, Aponil, Nimesin, Remesulide and others)
Release form - tablets of 100 mg, granules for suspension for oral administration in a sachet containing 1 dose of the drug - 100 mg each, gel in a tube.
A highly selective COX-2 inhibitor with a pronounced anti-inflammatory, analgesic and antipyretic effect.
Take the drug inside 100 mg twice a day, after meals. The duration of treatment is determined individually. The gel is applied to the affected area, gently rubbing into the skin. Multiplicity of application - 3-4 times a day.
When prescribing Nimesulide to elderly patients, dose adjustment of the drug is not required. The dose should be reduced in case of severe impairment of the patient's liver and kidney function. May have a hepatotoxic effect, inhibiting liver function.
During pregnancy, especially in the 3rd trimester, it is strongly not recommended to take nimesulide. During lactation, the drug is also contraindicated.
Nabumeton (Synmeton)
Release form - tablets of 500 and 750 mg.
Non-selective COX inhibitor.
A single dose for an adult patient is 500-750-1000 mg during or after a meal. In especially severe cases, the dose may be increased to 2 grams per day.
Side effects and contraindications are similar to those of other non-selective NSAIDs.
It is not recommended to take during pregnancy and lactation.
Combined non-steroidal anti-inflammatory drugs
There are drugs containing two or more active substances from the NSAID group, or NSAIDs in combination with vitamins or other drugs. The main ones are listed below.
- Dolaren. Contains 50 mg diclofenac sodium and 500 mg paracetamol. In this preparation, the pronounced anti-inflammatory effect of diclofenac is combined with the bright analgesic effect of paracetamol. Take the drug inside 1 tablet 2-3 times a day after meals. The maximum daily dose is 3 tablets.
- Neurodiclovitis. Capsules containing 50 mg of diclofenac, vitamin B1 and B6, and 0.25 mg of vitamin B12. Here, the analgesic and anti-inflammatory effect of diclofenac is enhanced by B vitamins, which improve metabolism in the nervous tissue. The recommended dose of the drug is 1-3 capsules per day in 1-3 doses. Take the drug after meals with plenty of fluids.
- Olfen-75, produced in the form of a solution for injection, in addition to diclofenac in an amount of 75 mg, also contains 20 mg of lidocaine: due to the presence of the latter in the solution, injections of the drug become less painful for the patient.
- Fanigan. Its composition is similar to that of Dolaren: 50 mg diclofenac sodium and 500 mg paracetamol. It is recommended to take 1 tablet 2-3 times a day.
- Flamidez. Very interesting, different drug. In addition to 50 mg of diclofenac and 500 mg of paracetamol, it also contains 15 mg of serratiopeptidase, which is a proteolytic enzyme and has a fibrinolytic, anti-inflammatory and anti-edematous effect. Available in the form of tablets and gel for topical use. The tablet is taken orally, after a meal, with a glass of water. As a rule, appoint 1 tablet 1-2 times a day. The maximum daily dose is 3 tablets. The gel is used externally, applying it to the affected area of the skin 3-4 times a day.
- Maxigesic. A drug similar in composition and action to Flamidez, described above. The difference lies in the manufacturing company.
- Diplo-P-Pharmeks. The composition of these tablets is similar to the composition of Dolaren. The dosages are the same.
- Dolar. Same.
- Dolex. Same.
- Oksalgin-DP. Same.
- Cinepar. Same.
- Diclocaine. Like Olfen-75, it contains diclofenac sodium and lidocaine, but both active ingredients are in half the dosage. Accordingly, it is weaker in action.
- Dolaren gel. Contains diclofenac sodium, menthol, linseed oil and methyl salicylate. All these components to some extent have an anti-inflammatory effect and potentiate the effects of each other. The gel is applied to the affected areas of the skin 3-4 times a day.
- Nimid forte. Tablets containing 100 mg of nimesulide and 2 mg of tizanidine. This drug successfully combines the anti-inflammatory and analgesic effects of nimesulide with the muscle relaxant (muscle relaxing) effect of tizanidine. Applicable for acute pain caused by spasm skeletal muscle(popularly - with infringement of the roots). Take the drug inside after eating, drinking plenty of fluids. The recommended dose is 2 tablets per day in 2 divided doses. The maximum duration of treatment is 2 weeks.
- Nizalid. Like nimid forte, it contains nimesulide and tizanidine in similar dosages. The recommended doses are the same.
- Alit. Soluble tablets containing 100 mg of nimesulide and 20 mg of dicycloverine, which is a muscle relaxant. It is taken orally after a meal with a glass of liquid. It is recommended to take 1 tablet 2 times a day for no longer than 5 days.
- Nanogan. The composition of this drug and the recommended dosages are similar to those of the drug Alit described above.
- Oksigan. Same.
Osteoarthritis, rheumatoid arthritis and other diseases of the joints and spine, occurring with pain and inflammation.
Peculiarities: all drugs in this group act on a similar principle and cause three main effects: analgesic, anti-inflammatory and antipyretic.
In different drugs, these effects are expressed to varying degrees, so some drugs are better suited for the long-term treatment of joint diseases, others are mainly used as painkillers and antipyretics.The most common side effects: allergic reactions, nausea, abdominal pain, erosion and ulcers of the mucous membrane of the gastrointestinal tract.
Main contraindications: individual intolerance, exacerbation of peptic ulcer of the stomach and duodenum.
Important information for the patient:
Drugs that have a pronounced analgesic effect and a significant number of side effects (diclofenac, ketorolac, nimesulide and others) can only be used as directed by a doctor.
Among non-steroidal anti-inflammatory drugs, a group of so-called "selective" drugs is distinguished, which are less likely to have side effects from the gastrointestinal tract.
Even over-the-counter pain relievers cannot be used long-term. If they are required frequently, several times a week, it is necessary to be examined by a doctor and treated according to the recommendations of a rheumatologist or neurologist.
In some cases, long-term use of this group of drugs requires additional intake of proton pump inhibitors that protect the stomach.
| Trade name of the drug | Price range (Russia, rub.) | Features of the drug, which is important for the patient to know |
| Active substance: diclofenac | ||
| Voltaren(Novartis) | A powerful pain reliever, mainly used for back and joint pain. It is undesirable to use for a long time, as the drug has numerous side effects. May adversely affect liver function, cause headache, dizziness and tinnitus. Contraindicated in "aspirin" asthma, disorders of hematopoiesis and blood coagulation processes. Do not use during pregnancy, breastfeeding and children under 6 years of age. | |
| diclofenac(various manufacturers) | ||
| Naklofen(Krka) | ||
| Ortofen(various manufacturers) | ||
| Rapten Rapid(Stada) | ||
| Active substance: Indomethacin | ||
| Indomethacin(various manufacturers) | 11,4-29,5 | It has a powerful anti-inflammatory and analgesic effect. However, it is considered quite outdated, as it leads in the likelihood of developing a variety of side effects. It has many contraindications, including the III trimester of pregnancy, the age of up to 14 years. |
| Metindol retard(Polfa) | 68-131,5 | |
| Active substance: diclofenac + paracetamol | ||
| Panoksen(Oxford Laboratories) | 59-69 | A powerful two-component pain reliever. Used to reduce severe pain and inflammation in arthritis, osteoarthritis, osteochondrosis, lumbago, dental and other diseases. Side effects - like diclofenac. Contraindications are inflammatory bowel disease, severe hepatic, renal and cardiac failure, the period after coronary artery bypass grafting, progressive kidney disease, active liver disease, pregnancy, period breastfeeding, childhood. |
| Active substance: Tenoxicam | ||
| Texamen(Mustafa Nevzat Ilach Sanai) | 186-355 | It has a powerful analgesic and anti-inflammatory effect, the antipyretic effect is less pronounced. Distinctive feature the drug is a long duration of action: more than a day. Indications are radicular syndrome in osteochondrosis, osteoarthritis with inflammation in the joints, neuralgia, muscle pain. Has a number of side effects. Contraindicated in bleeding from the gastrointestinal tract, pregnancy and during breastfeeding. |
| Active substance: Ketoprofen | ||
| artrosilene(Dompe Pharmaceuticals) | 154-331 | A drug with a pronounced analgesic and anti-inflammatory effect. Does not adversely affect the condition of the articular cartilage. Indications for use are symptomatic therapy of various arthritis, osteoarthritis, gout, headache, neuralgia, sciatica, muscle pain, post-traumatic and postoperative pain, pain syndrome during oncological diseases, painful periods. It causes many side effects and has many contraindications, including the III trimester of pregnancy and breastfeeding. In children, age restrictions depend on the trade name of the drug. |
| Quickcaps(Medana pharma) | 161-274 | |
| Ketonal (Lek. d.d.) | 93-137 | |
| Ketonal duo(Lek. d. d.) | 211,9-295 | |
| Oki (Dompe Pharmaceuticals) | 170-319 | |
| Flamax(Sotex) | 86,7-165,8 | |
| Flamax forte(Sotex) | 105-156,28 | |
| Flexen(Italfarmaco) | 97-397 | |
| Active substance: Dexketoprofen | ||
| Dexalgin(Berlin-Chemie/Menarini) | 185-343 | New powerful drug of short-term action. The analgesic effect occurs 30 minutes after taking the drug and lasts from 4 to 6 hours. Indications for use are acute and chronic inflammatory diseases of the musculoskeletal system (rheumatoid arthritis, spondyloarthritis, arthrosis, osteochondrosis), pain during menstruation, toothache. Side effects and contraindications are similar to those of other drugs. In general, with short-term use according to indications and at recommended doses, it is well tolerated. |
| Active substance: Ibuprofen | ||
| Ibuprofen(various manufacturers) | 5,5-15,9 | It is most often used as an antipyretic drug and a remedy for relieving headaches. However, in large doses it can also be used for diseases of the spine, joints and to relieve pain after bruises and other injuries. There may be side effects from the gastrointestinal tract, hematopoietic organs, as well as headache, dizziness, insomnia, increased blood pressure and a number of other undesirable reactions. It has many contraindications. Can not be used in the III trimester of pregnancy and while breastfeeding, in the I and II trimester it must be used with caution, only on the advice of a doctor. cha. |
| Burana (Orion Corporation) | 46,3-98 | |
| Ibufen (Polfa, Medana pharma) | 69-95,5 | |
| Moment (Berlin-Chemie/Menarini) | 71,6-99,83 | |
| Nurofen(Reckitt Benckiser) | 35,65-50 | |
| Nurofen Ultracap(Reckitt Benckiser) | 116-122,56 | |
| Nurofen Express(Reckitt Benckiser) | 102-124,4 | |
| Nurofen Express Neo(Reckitt Benckiser) | 65-84 | |
| Faspik(Zambon) | 80-115 | |
| Active substance: ibuprofen + paracetamol | ||
| Ibuklin(Dr. Reddy's) | 78-234,5 | Combined preparation containing two analgesic and antipyretic substances. It works more powerful than the same drugs taken separately. It can be used for pain in the joints and spine, injuries. However, it does not have a very pronounced anti-inflammatory effect, therefore, it is not recommended for long-term treatment in rheumatic diseases. It has many side effects and contraindications. Do not use in children under 12 years of age, as well as in the III trimester of pregnancy and while breastfeeding. |
| Brustan(Ranbaxi) | 60-121 | |
| Next(Pharmstandard) | 83-137 | |
| Active substance: Nimesulide | ||
| nise(Dr. Reddy's) | 111-225 | Selective analgesic drug, mainly used for back and joint pain. May also relieve period pain, headaches and toothaches. It has a selective effect, therefore it has less negative effect on the gastrointestinal tract. However, it has a number of contraindications and side effects. It is contraindicated during pregnancy and lactation; in children, age restrictions depend on the trade name of the drug. |
| Nimesulide(various manufacturers) | 65-79 | |
| Aponil(Medochemi) | 71-155,5 | |
| Nemulex(Sotex) | 125-512,17 | |
| Nimesil(Berlin-Chemie/Menarini) | 426,4-990 | |
| Nimika (IPKA) | 52,88-179,2 | |
| Nimulid(Panacea Biotek) | 195-332,5 | |
| Active substance: Naproxen | ||
| Nalgezin(Krka) | 104-255 | A powerful drug. It is used to treat arthritis, osteoarthritis, adnexitis, exacerbation of gout, neuralgia, sciatica, pain in the bones, tendons and muscles, headache and toothache, pain in cancer and after surgery. It has quite a few contraindications and can cause a variety of side effects, so long-term treatment is possible only under the supervision of a doctor. |
| Naproxen(Pharmstandard) | 56,5-107 | |
| Naproxen-acry (Akrikhin) | 97,5-115,5 | |
| Active substance: Naproxen + esomeprazole | ||
| Vimovo(AstraZeneca) | 265-460 | Combination preparation containing naproxen with analgesic and anti-inflammatory action and proton pump inhibitor esomeprazole. Developed in the form of tablets with sequential delivery of substances: the shell contains immediate release esomeprazole magnesium, and the core contains sustained release enteric-coated naproxen. As a result, esomeprazole is released in the stomach before naproxen dissolves, which protects the gastric mucosa from the possible negative effects of naproxen. Indicated for symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in patients at risk of gastric and duodenal ulcers. Despite good protective properties against the stomach, it can cause a number of other side effects. Contraindicated in severe liver, heart and kidney failure, gastrointestinal and other bleeding, cerebral hemorrhage and a number of other diseases and conditions. Not recommended in the III trimester of pregnancy, while breastfeeding and children under 18 years of age. |
| Active substance: Amtolmetin guacil | ||
| Nizilat(Dr. Reddy's) | 310-533 | A new non-steroidal anti-inflammatory drug with a minimal negative effect on the gastric mucosa. Despite a number of possible side effects, it was generally well tolerated by patients (including long-term use for 6 months). It can be used both for rheumatic diseases (rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout, etc.), and for the treatment of pain syndromes of other origin. It has a lot of contraindications. Not applicable during pregnancy, breastfeeding and under the age of 18 years. |
| Active substance: Ketorolac | ||
| Ketanov(Ranbaxi) | 214-286,19 | One of the most potent analgesics. because of a large number contraindications and side effects should be used occasionally and only in cases of very severe pain. |
| Ketorol(Dr. Reddy's) | 12,78-64 | |
| Ketorolac(various manufacturers) | 12,1-17 | |
| Active substance: Lornoxicam | ||
| Xefocam(Nycomedes) | 110-139 | It has a pronounced analgesic and anti-inflammatory effect. Indicated for short-term treatment of pain, including rheumatic diseases (rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout, etc.). It has many side effects and contraindications. |
| Xefokam Rapid(Nycomedes) | 192-376 | |
| Active substance: Aceclofenac | ||
| Aertal(Gideon Richter) | 577-935 | It has a good anti-inflammatory and analgesic effect. It contributes to a significant reduction in the severity of pain, morning stiffness, swelling of the joints, does not adversely affect cartilage tissue. It is used to reduce inflammation and pain in lumbago, toothache, rheumatoid arthritis, osteoarthritis and a number of other rheumatological diseases. Causes many side effects. Contraindications are similar to those of Panoxen. Do not use during pregnancy, lactation and in children under 18 years of age. |
| Active substance: Celecoxib | ||
| Celebrex(Pfizer, Searl) | 365,4-529 | One of the most selective (selectively acting) drugs of this group, which has a minimal negative effect on the gastrointestinal tract. Indications for use are symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, back pain, bone and muscle pain, postoperative, menstrual and other types of pain. May cause swelling, dizziness, cough, and a number of other side effects. It has many contraindications for use, including class II-IV heart failure, clinically significant coronary heart disease, peripheral arterial disease and severe cerebrovascular disease. Not applicable during pregnancy, breastfeeding and under the age of 18 years. |
| Active substance: Etoricoxib | ||
| Arcoxia(Merck Sharp & Dome) | 317-576 | Potent selective drug. The mechanism of action, side effects and contraindications is similar to celecoxib. Indications for use are osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute gouty arthritis. |
| Active substance: Meloxicam | ||
| Amelotex(Sotex) | 52-117 | A modern selective drug with a pronounced anti-inflammatory effect. Indications for use are pain and inflammatory syndrome in osteoarthritis, osteochondrosis, rheumatoid arthritis and ankylosing spondylitis. It is not usually used for antipyretic purposes and for the treatment of other types of pain. It can cause a variety of side effects, but the negative effect on the gastrointestinal tract is less than that of non-selective drugs in this group. It has many contraindications, including pregnancy, lactation and children under 12 years of age. |
| Artrozan(Pharmstandard) | 87,7-98,7 | |
| Bi-xicam(Veropharm) | 35-112 | |
| Meloxicam(various manufacturers) | 9,5-12,3 | |
| Mirloks(Polfa) | 47-104 | |
| Movalis(Boehringer Ingelheim) | 418-709 | |
| Movasin(Synthesis) | 73,1-165 | |
Remember, self-medication is life-threatening, for advice on the use of any medicines see a doctor.
Undoubtedly, the most important mechanism of action of NSAIDs is the ability to inhibit COX - an enzyme that catalyzes the conversion of free polyunsaturated fatty acids (for example, arachidonic) into prostaglandins (PG), as well as other eicosanoids - thromboxanes (TrA2) and prostacyclin (PG-I2) (Fig. one). It is proved that prostaglandins have versatile biological activity:
a) are mediators of the inflammatory response: they accumulate in the focus of inflammation and cause local vasodilation, edema, exudation, migration of leukocytes and other effects (mainly PG-E2 and PG-I2);
b) sensitize receptors to mediators of pain (histamine, bradykinin) and mechanical influences, lowering the threshold of sensitivity;
in) increase the sensitivity of the hypothalamic centers of thermoregulation to the action of endogenous pyrogens (interleukin-1, etc.) formed in the body under the influence of microbes, viruses, toxins (mainly PG-E2);
G) play an important physiological role in protecting the mucous membrane of the gastrointestinal tract(increased secretion of mucus and alkali; preservation of the integrity of endothelial cells inside the microvessels of the mucosa, contributing to the maintenance of blood flow in the mucosa; preservation of the integrity of granulocytes and, thus, the preservation of the structural integrity of the mucosa);
e) affect kidney function: cause vasodilation, maintain renal blood flow and glomerular filtration rate, increase renin release, sodium and water excretion, participate in potassium homeostasis.
Fig.1. "Cascade" of metabolic products of arachidonic acid and their main effects.
Note: * - LT-S 4 , D 4 , E 4 are the main biological components of the slowly reacting anaphylaxis substance MPS-A (SRS-A).
In recent years, it has been established that there are at least two cyclooxygenase isoenzymes that are inhibited by NSAIDs. The first isoenzyme, COX-1, controls the production of PGs that regulate the integrity of the gastrointestinal mucosa, platelet function, and renal blood flow, and the second isoenzyme, COX-2, is involved in the synthesis of PGs during inflammation. Moreover, COX-2 is absent under normal conditions, but is formed under the influence of some tissue factors that initiate an inflammatory reaction (cytokines and others). In this regard, it is assumed that the anti-inflammatory effect of NSAIDs is due to inhibition of COX-2, and their undesirable reactions - inhibition of COX-1. The ratio of the activity of NSAIDs in terms of blocking COX-1 / COX-2 makes it possible to judge their potential toxicity. The smaller this value, the more selective the drug in relation to COX-2 and, thus, less toxic. For example, for meloxicam it is 0.33, diclofenac - 2.2, tenoxicam - 15, piroxicam - 33, indomethacin - 107.
The latest data indicate that NSAIDs not only inhibit cyclooxygenase metabolism, but also actively influence PG synthesis associated with Ca mobilization in smooth muscles. Thus, butadione inhibits the conversion of cyclic endoperoxides into prostaglandins E2 and F2, and fenamates can also block the reception of these substances in tissues.
An important role in the anti-inflammatory action of NSAIDs is played by their influence on the metabolism and bioeffects of kinins. In therapeutic doses, indomethacin, orthophene, naproxen, ibuprofen, acetylsalicylic acid (ASA) reduce the formation of bradykinin by 70-80%. This effect is based on the ability of NSAIDs to provide nonspecific inhibition of the interaction of kallikrein with high molecular weight kininogen. NSAIDs cause chemical modification of the components of the kininogenesis reaction, as a result of which, due to steric hindrances, the complementary interaction of protein molecules is disrupted and effective hydrolysis of high-molecular kininogen by kallikrein does not occur. A decrease in the formation of bradykinin leads to inhibition of the activation of -phosphorylase, which leads to a decrease in the synthesis of arachidonic acid and, as a result, the manifestation of the effects of its metabolic products, shown in Fig. one.
No less important is the ability of NSAIDs to block the interaction of bradykinin with tissue receptors, which leads to the restoration of disturbed microcirculation, a decrease in capillary hyperextension, a decrease in the release of the liquid part of the plasma, its proteins, pro-inflammatory factors and formed elements, which indirectly affects the development of other phases of the inflammatory process. Since the kallikrein-kinin system plays the most important role in the development of acute inflammatory reactions, the NSAIDs are most effective in the early stages of inflammation in the presence of a pronounced exudative component.
Inhibition of the release of histamine and serotonin, blockade of tissue reactions to these biogenic amines, which play a significant role in the inflammatory process, have a certain significance in the mechanism of the anti-inflammatory action of NSAIDs. The intramolecular distance between the reaction centers in the molecule of antiphlogistics (compounds of the butadione type) approaches those in the molecule of inflammatory mediators (histamine, serotonin). This suggests the possibility of competitive interaction of the mentioned NSAIDs with receptors or enzyme systems involved in the processes of synthesis, release and transformation of these substances.
As mentioned above, NSAIDs have a membrane-stabilizing effect. By binding to the G-protein in the cell membrane, antiphlogistics affect the transmission of membrane signals through it, inhibit the transport of anions, and affect biological processes that depend on the overall mobility of membrane lipids. They realize their membrane-stabilizing effect by increasing the microviscosity of membranes. Penetrating through the cytoplasmic membrane into the cell, NSAIDs also affect the functional state of the membranes of cell structures, in particular lysosomes, and prevent the pro-inflammatory effect of hydrolases. Data were obtained on the quantitative and qualitative features of the affinity of individual drugs for the protein and lipid components of biological membranes, which can explain their membrane effect.
One of the mechanisms of damage to cell membranes is free radical oxidation. Free radicals generated during lipid peroxidation play an important role in the development of inflammation. Therefore, the inhibition of NSAID peroxidation in membranes can be considered as a manifestation of their anti-inflammatory action. It should be borne in mind that one of the main sources of free radical generation is the metabolism of arachidonic acid. Individual metabolites of its cascade cause the accumulation of polymorphonuclear neutrophils and macrophages in the focus of inflammation, the activation of which is also accompanied by the formation of free radicals. NSAIDs, by acting as scavengers for these compounds, offer a new approach to the prevention and treatment of tissue damage caused by free radicals.
In recent years, studies of the effect of NSAIDs on the cellular mechanisms of the inflammatory response have received significant development. NSAIDs reduce cell migration to the site of inflammation and reduce their phlogogenic activity, and the effect on polymorphonuclear neutrophils correlates with inhibition of the lipoxygenase pathway of arachidonic acid oxidation. This alternative arachidonic acid pathway leads to the formation of leukotrienes (LT) (Fig. 1), which meet all the criteria for inflammatory mediators. Benoxaprofen has the ability to influence 5-LOG and block the synthesis of LT.
Less studied is the effect of NSAIDs on the cellular elements of the late stage of inflammation - mononuclear cells. Some NSAIDs reduce the migration of monocytes that produce free radicals and cause tissue destruction. Although important role cellular elements in the development of the inflammatory response and the therapeutic effect of anti-inflammatory agents is undoubted, the mechanism of action of NSAIDs on the migration and function of these cells is still to be clarified.
There is an assumption about the release of NSAIDs of natural anti-inflammatory substances from the complex with plasma proteins, which comes from the ability of these drugs to displace lysine from its association with albumin.
