1. Selective inhibitors of COX-1 - acetylsalicylic acid in small doses.
2. Non-selective inhibitors of COX-1 and COX-2 - the majority of NSAIDs.
3. Drugs with a predominant effect on COX-2 - meloxicam, nimesulide.
4. Highly selective COX-2 inhibitors - celecoxib, rofecoxib.
Pharmacodynamics. The main mechanism of the anti-inflammatory action of NSAIDs, as well as antipyretic analgesics, is the inhibition of cyclooxygenase (COX), a key enzyme involved in the conversion of arachidonic acid to endoperoxides, from which prostaglandins and thromboxane are synthesized.
In the focus of inflammation, under the influence of various damaging factors, the enzyme phospholipase A, (PLA,) is activated, under the influence of which arachidonic acid is released from the phospholipids of cell membranes. Prostaglandins (PG) are mediators and modulators of inflammation, pain and fever.
Inhibition of COX sharply reduces the level of PG responsible for the main symptoms of inflammation: edema, vasodilation, fever, pain, i.e. the therapeutic target of anti-inflammatory drugs is the COX enzyme: COX-1, COX-2 and COX-3. The first takes part in the most important physiological processes, in particular in the synthesis of prostacyclin and other prostaglandins that regulate the integrity of the mucous membrane of the gastrointestinal tract, platelet function and blood circulation in the kidneys. The level of COX-2 is low under normal conditions and increases under the influence of cytokines and other anti-inflammatory agents. This enzyme is involved in the synthesis of prostanoids necessary for the development and maintenance of inflammation, therefore, the anti-inflammatory effect of non-steroidal anti-inflammatory drugs is due to the inhibition of COX-2, and side reactions - COX-1, COX-3 function in the structures of the central nervous system.
For new generation drugs (meloxicam, mesulide, tenoxicam, lorioxicam, elderin, solpaflex, nabumeton, etc.), the mechanism of action differs from traditional NSAIDs in the selective inhibition of PG, which leads to a pronounced anti-inflammatory activity of new drugs and, at the same time, to a low degree of development complications with long-term use.
Celecoxib is a highly selective specific inhibitor of COX-2; it has a very low affinity for COX-1, therefore it does not affect the synthesis of those PGs that are responsible for physiological processes in the gastric mucosa and platelets.
The mechanism of action of NSAIDs is also associated with many links in the pathogenesis of inflammation, pain and fever and includes a number of processes.
Thus, inhibition of the exudative phase of inflammation by anti-inflammatory drugs is a consequence of a decrease in the activity of inflammatory mediators - PG, bradykinin, histamine, serotonin, which leads to a decrease in the permeability of the vascular wall. During inflammation, PG and other inflammatory mediators are released and interact.
Prostaglandins sensitize nocireceptors, vessels, tissues, and increase reactivity to the action of nonspecific inflammatory mediators (histamine, serotonin, kinins, complement, microsomal enzymes). In turn, histamine plays the role of an inflammation trigger, expands microvessels, and increases their permeability.
Serotonin also increases vascular permeability. Kinins can cause the main manifestations of inflammation - vasodilation, pain, increase the corresponding effects of histamine and serotonin, PGE biosynthesis, and PGE2. Along with the mediator role, PGs can be modulators of inflammation, affecting platelet aggregation (inhibiting thromboxane biosynthesis). In the later stages, complement, lysosomal enzymes, and other mediators (kinins, leukotrienes) are involved in inflammation. An important component The mechanism of action is a local effect: they prevent the release of lysosomal enzymes from the cell and reduce the degree of development of the inflammatory process.
The anti-hyaluronidase activity of NSAIDs also helps to reduce the permeability (anti-edematous effect) of blood vessels and cell membranes in the focus of inflammation.
Non-steroidal anti-inflammatory drugs inhibit oxidative phosphorylation, which disrupts the synthesis of glycosaminoglycans, and this inhibits proliferation processes; inhibits the development of the fibrous phase of inflammation in rheumatism.
By inhibiting free radical reactions, NSAIDs reduce the level of oxygen free radicals that damage cell membranes at the site of inflammation and contribute to its spread.
These anti-inflammatory drugs block the formation of ATP and thereby reduce the energy supply of the inflammatory response.
A decrease in the intensity of the inflammatory reaction, tissue edema under the influence of NSAIDs is accompanied by a decrease in pain. By reducing the formation of PGE and PGE2, NSAIDs reduce their potentiating effect on pain receptors and the flow of pain impulses into the central nervous system. In addition, drugs of this group limit the accumulation of PG in the brain structures involved in the perception of pain. This leads to a reduction in pain, especially associated with an inflammatory response - a central mechanism. The significance of the anti-inflammatory properties of NSAIDs in reducing pain is also due to purely mechanical factors. Reducing edema reduces pressure on baroreceptors, helps to relieve pain - a peripheral mechanism.
The antipyretic effect of NSAIDs is associated with their ability to inhibit the synthesis of PG and other pyrogens that cause a hyperthermic reaction, as well as with an inhibitory effect on the central mechanisms of the temperature reaction. NSAIDs reduce the content of PG in the cerebrospinal fluid and reduce the activating effect of pyrogens on the thermoregulatory center in the hypothalamus. This causes an increase in heat transfer and increased sweating due to a decrease in body temperature.
Amizon has an immunomodulatory effect, enhancing humoral and cellular immunity, influencing the factors of natural antimicrobial resistance (lysozyme level). Amizon is an active oral inducer of endogenous interferon. Mefenamic acid also has immunomodulatory properties.
Non-steroidal anti-inflammatory drugs (acetylsalicylic acid, lysine acetylsalicylate, ketoprofen, diclofenac sodium, nifedipic acid, indomethacin, artrotek, anapirin) also have an antiplatelet effect. The desensitizing effect is characteristic of indomethacin, diclofenac sodium, acetylsalicylic acid.
According to the degree of anti-inflammatory activity, NSAIDs can be arranged as follows: indomethacin = diclofenac > meloxicam > nimesulide > piroxicam > ketoprofen > naproxen > ibuprofen > acetylsalicylic acid.
The non-narcotic analgesic paracetamol (paracetaminophen) has a high analgesic and antipyretic activity, but it has practically no anti-inflammatory effect. Already in small doses, it inhibits the COX-3 isoform in the structures of the central nervous system and does not affect this enzyme in peripheral tissues.
Salicylates[Edit]
Acetylsalicylic acid(aspirin) - NSAID used in the clinic for over 100 years. Nowadays, about 50 thousand tons of aspirin are produced annually.
Pharmacokinetics. Acetylsalicylic acid (ASA) is absorbed in the stomach and upper small intestine. The latent period is 30 minutes, the maximum content in the blood plasma is observed after 2 hours, the duration of action is 4-6 hours. As an anti-inflammatory agent, ASA is prescribed in a daily dose of 3-4 g (up to 6 g). The kinetics of ASA depends on the dose: when used at a dose of 300-400 mg, its plasma level increases proportionally, with an increase in a single dose of the drug to 1-2 g, its concentration in the blood plasma increases disproportionately quickly, which can lead to the development of intoxication, so a single dose should not exceed 1 g.
It is used for rheumatism, infectious-allergic myocarditis, rheumatoid arthritis, systemic lupus erythematosus, etc. Salicylic acid derivatives are used mainly for inflammatory processes and pain syndromes of moderate strength (myositis, myalgia, arthralgia, neuralgia, toothache, headache, dysmenorrhea). As an antiplatelet agent, ASA acts on the initial phase of thrombus formation in small doses - 0.08-0.3 g per day or every other day. In such doses, the drug disrupts the synthesis of thromboxane A, by acetylation of COX. The antiplatelet effect persists for 4-7 days, since the inhibitory effect on platelet COX is irreversible. In the indicated doses, ASA is prescribed to prevent postoperative blood clots, in the presence of thrombophlebitis, retinal vascular thrombosis, cerebrovascular accidents, as well as to prevent thrombotic complications in angina pectoris and myocardial infarction.
Lysine acetylsalicylate - a water-soluble form of ASA - is used for parenteral administration.
ben gay- a combined preparation of the salicylates group, which includes methyl salicylate and menthol, exhibits a pronounced analgesic and warming effect. Used for topical application for muscle and joint pain. In the form of an ointment, a sports balm is used to relieve muscle tension before and after training, as well as to relieve pain in myalgia and arthralgia.
Side effects: complications of salicylates therapy are associated with irritation of the mucous membrane. Blockade of mucosal PGs that inhibit secretion hydrochloric acid and increase the secretion of mucus, leading to an exacerbation of gastric ulcer. Possible development of allergic reactions in the form of a rash, attacks of bronchial asthma, anaphylactic shock. In pregnant women, Moiyr salicylates delay the onset of labor; at the end of pregnancy, they can contribute to premature occlusion of the ductus botulinum, which leads to the birth of a child with a corresponding cardiac pathology. In cases of prolonged use, chronic poisoning develops - salicism, characterized by headache, hearing loss, impaired consciousness, depression, drowsiness, nausea, vomiting, diarrhea, respiratory alkalosis. These negative phenomena disappear after the abolition of ASA. Acute ASA poisoning can develop if a single dose exceeds 2 g (in children - 1 g). The described symptoms are accompanied by fever, anxiety, hallucinations, mania, convulsions, coma. Dehydration and ketosis, metabolic acidosis are observed, hemorrhages develop. Such patients are subject to treatment in a hospital in order to eliminate dehydration, acid-base balance disorders. To remove ASA from the body, the stomach is washed with a solution of sodium bicarbonate, adsorbents are prescribed, forced diuresis, peritoneal dialysis or hemodialysis are carried out. Vikasol, a solution of sodium bicarbonate, glucose, potassium chloride are administered intravenously; carry out a blood transfusion, cover the patient with a compress with ice.
Phenylbutazone (butadione) differs from other pyrazolones by a more pronounced anti-inflammatory activity than salicylates, but the analgesic and antipyretic effects of butadione are weaker than those of them. The main complications when using the drug are violations of hematopoiesis: aplastic anemia, agranulocytosis, thrombocytopenia.
When taking butadione and other NSAIDs, the repair of cartilage of the joints and subchondria of bone tissue is disrupted, which can lead to the formation of foci of destruction and cysts. At the same time, NSAIDs reduce pain and synovitis, but do not delay degenerative-dystrophic changes in the tissues of the joints, so they are recommended to be used only during an exacerbation of the inflammatory process.
Given the presence a large number side effects, butadion is currently used for external use in the form of a 5% ointment.
Mefenamic acid is superior in analgesic action to ASA. Niflufenamic acid in the form of a gel and cream is more active than mefenamic acid.
Indomethacin has a pronounced anti-inflammatory, analgesic and antipyretic activity, it is used orally at 25-50 mg 2-3 times a day. Rapidly and almost completely absorbed from the intestine. The maximum effect develops after 2 hours, the half-life is 7 hours. Indomethacin is one of the most active anti-inflammatory drugs for rheumatoid arthritis, periarthritis, ankylostomosing spondylitis (Bechterew's disease), osteoarthritis, gout, inflammatory diseases of the connective tissue, musculoskeletal system, thrombophlebitis. Apply it long time, with a sharp withdrawal of the drug, the pathological process may worsen.
Side effects: occur in 25-50% of patients even when using the drug in small doses, especially in children under 7 years of age. Dyspeptic disorders are characteristic, it has an ulcerogenic effect. To prevent a negative effect on the gastrointestinal tract, the drug must be taken after meals, washed down with milk or sodium bicarbonate solution, and antacids should be used.
Indomethacin may cause migraine-like headache, dizziness, blurriness visual perception, depression. These phenomena are especially dangerous in persons whose profession requires a quick psychological and physical reaction. Sometimes the drug causes allergic reactions, granulocytopenia, liver and kidney damage. Contraindicated in peptic ulcer of the stomach and duodenum, in bronchial asthma. It should not be given to women during pregnancy and lactation. Indomethacin ointment combines a highly effective active ingredient and a convenient dosage form, which ensures high bioavailability of the drug, as well as the absence of systemic side effects.
ibuprofen- a derivative of propionic acid; the strength of the anti-inflammatory action is weaker than indomethacin. It has an analgesic and antipyretic effect. As an anti-inflammatory agent, it is used in a daily dose of 0.6-1.2 g. It is prescribed orally 3-4 times a day for rheumatoid arthritis, deforming osteoarthritis, ankylosing spondylosis, especially if patients cannot tolerate ASA. Ibuprofen sometimes causes dyspeptic disorders, allergic reactions. Cross-allergy with penicillin is possible. Cases of granulocytopenia have been described.
Diclofenac sodium (ortofen, voltaren)- a derivative of phenylacetic acid - surpasses ibuprofen in anti-inflammatory action, has analgesic and antipyretic effects and low toxicity, does not cause degradation of glycosaminoglycans and collagen in the joints. When taken orally, the maximum effect develops after 2 hours and lasts 6-7 hours. It is used for rheumatism, arthrosis, spondyloarthrosis. The drug is well tolerated, sometimes there are dyspeptic disorders, allergic reactions. With prolonged use, an ulcerogenic effect is possible. Contraindicated in peptic ulcer of the stomach and duodenum, in the first trimester of pregnancy. With prolonged use, it is necessary to control the blood picture.
Ketoprofen inhibits platelet aggregation, the anti-inflammatory effect in articular syndrome occurs by the end of the first week.
Piroxicam- a derivative of oxicam, has a strong anti-inflammatory effect, is well absorbed when taken orally. The maximum concentration in the blood is observed after 3-5 hours, the half-life is 48-50 hours, the daily dose is 20-40 mg (when it is increased to 60 mg, the effect increases, but the number of side effects also increases). Apply the drug 1-2 times a day. The risk of developing gastrointestinal bleeding is quite high, which is explained by a long half-life.
Lornoxicam slightly exceeds piroxicam in activity. Meloxicam predominantly affects COX-2 and causes fewer gastrointestinal side effects.
Main side effects that are observed with the use of NSAIDs - non-selective COX inhibitors, are presented in table 2.15.
The treatment of inflammatory diseases of the connective tissue of a rheumatoid nature is a difficult and complex process that requires the maintenance of a certain sequence. At the beginning of the disease, NSAIDs are used, the main purpose of their use is to suppress the inflammatory process, reduce pain, stiffness of muscles and joints. However, they do not change the course of the disease. Basic therapy drugs can modify the course of the disease.
Means of basic therapy used in the treatment of rheumatoid arthritis, systemic and other connective tissue diseases[Edit]
Delayed-type hypersensitivity plays an important role in the pathogenesis of these diseases. Its implementation involves cytotoxic T-lymphocytes that destroy cells that have antigens on their surface; sensitized T-lymphocytes, which, through their lymphokines, recruit monocytes, turning them into macrophages, activate the secretion and function of the latter, consisting in cytotoxicity, phagocytosis of damaged cells, etc. But in a pathologically altered synovial membrane of the joints (with rheumatoid arthritis) or connective tissue with it pathology, both immune complexes (i.e., Ig and components of the complement system) and macrophages, which release proteolytic enzymes, oxygen free radicals, various cytokines, etc., were found.
In the deployment of the pathological process, one of the key functions is performed by mono-kin - interleukin-1 (IL-1), produced by macrophages that infiltrate damaged tissues, and synoviacytes, acquiring this ability. Due to its increased formation, the synthesis of PGE2 and the function of neutrophils are activated; both stimulate latent proteases that destroy the synovial membrane of cartilage. At the same time, collagen metabolites are formed that have the properties of endogenous antigens, lymphocytes are activated, releasing various lymphokines, of which IL-2 should be noted, activating the proliferation of T-killer lymphocytes, as well as lymphokines that transmit sensitization to other cells, forming their clones.
In the treatment of systemic diseases of the connective tissue, the so-called basic antirheumatic drugs are used, which are characterized by the development of a slow effect - a few months after the start of treatment (hingamin, penicillinamine, gold preparations), cytostatics, and glucocorticoids.
Chingamine (delagil, chloroquine) introduced into medicine as an antimalarial agent, but it is able to suppress inflammatory reactions, in which an element of delayed-type hypersensitivity (DTH) is involved. Stabilizes cellular and subcellular membranes of lysosomes, limiting the release of hydrolases from them and thereby inhibiting the alteration phase of normal inflammation. In addition, hingamin inhibits the activity of nucleic acids (introducing between their base pairs), in particular lymphocytes, inhibits their production of lymphokines, including IL-2, as a result, the activity and division of T-lymphocytes decreases, the stimulating effect of T-helpers on the division of monocytes , their production of IL-1. As a result, the inflammatory process that occurs due to the ingress of antigen into the connective tissue of the joint gradually fades. It is used for continuously recurrent rheumatism, moderate form of rheumatoid arthritis, systemic lupus erythematosus and some other diseases of this kind. The therapeutic effect develops slowly (after 10-12 weeks) with daily administration of the drug. Treatment should be long - at least 6 months, usually 1-2 years.
Such a long-term administration of the drug may be accompanied by the occurrence of undesirable effects associated with the accumulation of the drug in tissues (inhibition of gastric juice secretion, impaired liver function, dermatitis, leukopenia, myopathy). The most dangerous is retinopathy, which can lead to blindness, therefore, when using the drug, it is necessary to regularly monitor the sharpness and size of the visual field, prescribe hydrochloric acid with pepsin, non-steroidal anabolic agents (orotic acid, carnitine, etc.).
Penicillamine (cuprenil)- product of penicillin metabolism; contains a sulfhydryl group capable of binding many substances, including heavy metals. It is believed that penicillamine forms complex compounds with copper, thereby facilitating its delivery to inflammation sites, in which both its content and superoxide dismutase activity are usually reduced, eliminating excess oxygen free radicals released in the inflammation site and damaging the membranes of neighboring cells. Forming complex compounds with iron, penicillamine limits its catalytic role in the formation of an extremely active oxygen radical (OH). In addition, it inhibits the formation of antigens of the collagen structure.
Penicillamine is used primarily in the treatment of active progressive rheumatoid arthritis. The therapeutic effect appears after 12 weeks, a clear improvement - after 5-6 months. With long-term administration, undesirable effects are possible: rashes, dysfunction of the gastrointestinal tract, temporary loss of taste, thrombocytopenia (sometimes severe with hemorrhages), proteinuria (sometimes ending in the development of nephrotic syndrome).
Preparations of gold- krizanol, solganal, aurothioglucose, auronofin - disrupt antigen uptake by macrophages, prevent the release of interleukin-1 by monocytes and interleukin-2 by lymphocytes, inhibit the proliferation of T-lymphocytes, reduce the activity of T-helpers, the formation of Ig by B-lymphocytes, rheumatoid factor, immune complexes, inhibit the activation of the complement system.
These drugs are used to treat rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, and other collagen diseases. Solutions (krizanol, solganal - oil, aurothioglucose - water) are intended for parenteral administration (intramuscularly or directly into the area of the affected joint), auronofin is a drug for oral administration.
Injections of these drugs are made once a week (Auronofin is taken daily) for a long time. The first signs of improvement in the patient's condition may appear after 6-7 weeks, a distinct therapeutic effect occurs after 10-12 weeks. To obtain a more pronounced effect, gold preparations are prescribed simultaneously with non-steroidal anti-inflammatory drugs or glucocorticoids. It should be noted that in approximately 25-30% of patients these drugs are ineffective, but this can be judged after 6 months of their use.
Complications with the use of gold preparations: rash, ulcers on the oral mucosa, proteinuria, thrombocytopenia and occasionally pancytopenia, functional disorders of the liver are noted, with oral administration, a nitritoid crisis can sometimes occur. The oral drug is less dangerous, as it is excreted by the wall of the colon, accumulates less in the kidneys and liver.
Cytostatics(cyclophosphamide, chlorbugin, azathioprine less often - mercaptopurine, cyclosporine A) are used in the treatment of diffuse connective tissue diseases. By inhibiting cell division, including lymphoid tissue, they limit the formation of immunocompetent cells and the development of immunological mechanisms in rheumatoid arthritis, systemic lupus, etc. These drugs are considered as reserve ones, they are usually used when other slow-acting antirheumatoid drugs are ineffective.
They are sometimes prescribed in severe forms of the disease with HAT, since by inhibiting the division of T-lymphocytes, they disrupt their cooperation with B-lymphocytes, and consequently, the formation of immunoglobulins.
When prescribing cytostatics, serious complications are possible.
Cyclosporin A is an antibiotic, which is a cyclic peptide consisting of 11 amino acids. The drug is introduced into lymphocytes, binds to cytoplasmic and nuclear proteins, inhibiting the coding of the synthesis of lymphokines in activated T-lymphocytes, in particular interleukin-2, γ-interferon, a factor that inhibits the migration of macrophages, and their chemotaxis factor. In addition, it stimulates the function of monocytes (since it suppresses their activation by lymphokines), including the production of interleukin-1, and suppresses the generation of clans of cytostatic killer cells in relation to transplanted tissues. Very important is its ability to maintain and even increase the activity of T-suppressors, i.e. cyclosporine A promotes the manifestation of natural immunosuppression, suppresses the rejection of transplanted tissues and organs. It inhibits cell division in various tissues less than other cytostatics, and when it is used, there are fewer hematological and infectious complications.
Cyclosporine A is usually used in combination with prednisolone in the treatment of patients with glomerulonephritis, which allows to reduce the dose of prednisolone and reduce the number of exacerbations of this disease.
When prescribing cyclosporine A, it is necessary to maintain its level in the blood plasma no higher than 200-400 mg ml "1 in order to prevent the development of severe complications. At higher concentrations of cyclosporine A in the blood, the patient's blood supply to the kidneys may be impaired, diuresis, glomerular filtration, increase the level of potassium in the blood plasma and blood pressure, develop hyperchloremic acidosis, appear hypomagnesemia, manifested in the occurrence of tremors, seizures.In addition, when taking cyclosporine A, gingival hyperplasia, inhibition of the formation of prostacyclin by endothelial cells, which contributes to thrombosis, inhibition of liver function can be observed. With the ineffectiveness of NSAIDs and basic therapy, and in cases of a very severe course of the inflammatory process, glucocorticosteroids are used.
Non-steroidal anti-inflammatory drugs (NSAIDs, NSAIDs) are a group of drugs whose action is aimed at symptomatic treatment (pain relief, inflammation and temperature reduction) in acute and chronic diseases. Their action is based on a decrease in the production of special enzymes called cyclooxygenases, which trigger the reaction mechanism to pathological processes in the body, such as pain, fever, inflammation.
Medicines of this group are widely used all over the world. Their popularity is ensured by good efficiency against the background of sufficient safety and low toxicity.
Most famous representatives groups of NSAIDs are for most of us aspirin (), ibuprofen, analgin and naproxen, available in pharmacies in most countries of the world. Paracetamol (acetaminophen) is not an NSAID because it has a relatively weak anti-inflammatory activity. It acts against pain and temperature on the same principle (by blocking COX-2), but mainly only in the central nervous system, almost without affecting the rest of the body.
Soreness, inflammation and fever are common pathological conditions that accompany many diseases. If we consider the pathological course at the molecular level, we can see that the body "forces" the affected tissues to produce biologically active substances - prostaglandins, which, acting on the vessels and nerve fibers, cause local swelling, redness and pain.
In addition, these hormone-like substances, reaching the cerebral cortex, affect the center responsible for thermoregulation. Thus, impulses are given about the presence of an inflammatory process in tissues or organs, so a corresponding reaction occurs in the form of fever.
Responsible for triggering the mechanism for the appearance of these prostaglandins is a group of enzymes called cyclooxygenases (COX) . The main action of non-steroidal drugs is aimed at blocking these enzymes, which in turn leads to inhibition of the production of prostaglandins, which increase the sensitivity of nociceptive receptors responsible for pain. Consequently, painful sensations that bring suffering to a person, unpleasant sensations, are stopped.
Types behind the mechanism of action
NSAIDs are classified according to their chemical structure or mechanism of action. The long-known drugs of this group were divided into types according to their chemical structure or origin, since then the mechanism of their action was still unknown. Modern NSAIDs, on the contrary, are usually classified according to the principle of action - depending on what type of enzymes they act on.
There are three types of cyclooxygenase enzymes - COX-1, COX-2 and the controversial COX-3. At the same time, non-steroidal anti-inflammatory drugs, depending on the type, affect the main two of them. Based on this, NSAIDs are divided into groups:
- non-selective inhibitors (blockers) of COX-1 and COX-2- act immediately on both types of enzymes. These drugs block COX-1 enzymes, which, unlike COX-2, are constantly present in our body, performing various important functions. Therefore, exposure to them can be accompanied by various side effects, and a particular negative effect is on the gastrointestinal tract. This includes most classic NSAIDs.
- selective COX-2 inhibitors. This group affects only enzymes that appear in the presence of certain pathological processes, such as inflammation. Taking such drugs is considered safer and preferable. They do not affect the gastrointestinal tract so negatively, but at the same time, the load on the cardiovascular system is greater (they can increase pressure).
- selective NSAID COX-1 inhibitors. This group is small, since almost all drugs that affect COX-1 affect COX-2 to varying degrees. An example is acetylsalicylic acid in a small dosage.
In addition, there are controversial COX-3 enzymes, the presence of which has been confirmed only in animals, and they are also sometimes referred to as COX-1. It is believed that their production is slightly slowed down by paracetamol.
In addition to reducing fever and eliminating pain, NSAIDs are recommended for blood viscosity. The drugs increase the liquid part (plasma) and reduce formed elements, including lipids that form cholesterol plaques. Due to these properties, NSAIDs are prescribed for many diseases of the heart and blood vessels.
List of NSAIDs
Major non-selective NSAIDs
Acid derivatives:
- acetylsalicylic (aspirin, diflunisal, salasat);
- arylpropionic acid (ibuprofen, flurbiprofen, naproxen, ketoprofen, thiaprofenic acid);
- arylacetic acid (diclofenac, fenclofenac, fentiazac);
- heteroarylacetic (ketorolac, amtolmetin);
- indole/indene of acetic acid (indomethacin, sulindac);
- anthranilic (flufenamic acid, mefenamic acid);
- enolic, in particular oxicam (piroxicam, tenoxicam, meloxicam, lornoxicam);
- methanesulfonic (analgin).
Acetylsalicylic acid (aspirin) is the first known NSAID, discovered back in 1897 (all others appeared after the 1950s). In addition, it is the only agent capable of irreversibly inhibiting COX-1 and has also been shown to stop platelets from sticking together. Such properties make it useful in the treatment of arterial thrombosis and for the prevention of cardiovascular complications.
Selective COX-2 inhibitors
- rofecoxib (Denebol, Vioxx discontinued in 2007)
- Lumiracoxib (Prexige)
- parecoxib (Dynastat)
- etoricoxib (Arcosia)
- celecoxib (Celebrex).
Main indications, contraindications and side effects
Today, the list of NVPS is constantly expanding and new generation drugs are regularly supplied to the pharmacy shelves, capable of simultaneously lowering the temperature, relieving inflammation and pain in a short period of time. Due to the soft and gentle effect, the development of negative consequences in the form of allergic reactions, as well as damage to the organs of the gastrointestinal tract and urinary system.
Table. Non-steroidal anti-inflammatory drugs - indications
| property of a medical device | Diseases, pathological condition of the body |
| Antipyretic | High temperature (above 38 degrees). |
| Anti-inflammatory | Diseases of the musculoskeletal system - arthritis, arthrosis, osteochondrosis, muscle inflammation (myositis), spondyloarthritis. This also includes myalgia (often appears after a bruise, sprain, or soft tissue injury). |
| Painkiller | The drugs are used for menstrual and headaches (migraines), are widely used in gynecology, as well as for biliary and renal colic. |
| Antiplatelet agent | Cardiological and vascular disorders: ischemic heart disease, atherosclerosis, heart failure, angina pectoris. In addition, it is often recommended for the prevention of stroke and heart attack. |
Non-steroidal anti-inflammatory drugs have a number of contraindications that must be taken into account. Drugs are not recommended for treatment if the patient:
- peptic ulcer of the stomach and duodenum;
- kidney disease - limited intake is allowed;
- blood clotting disorder;
- the period of gestation and breastfeeding;
- Previously, pronounced allergic reactions to drugs of this group were observed.
In some cases, the formation of a side effect is possible, as a result of which the composition of the blood changes (a “fluidity” appears) and the walls of the stomach become inflamed.
The development of a negative result is explained by inhibition of the production of prostaglandins not only in the inflamed focus, but also in other tissues and blood cells. In healthy organs, hormone-like substances play an important role. For example, prostaglandins protect the lining of the stomach from the aggressive effects of digestive juice on it. Therefore, taking NVPS contributes to the development of gastric and duodenal ulcers. If a person has these diseases, and he still takes "illicit" drugs, then the course of the pathology can worsen up to perforation (breakthrough) of the defect.
Prostaglandins control blood clotting, so a lack of them can lead to bleeding. Diseases for which examinations should be carried out before prescribing a course of NVPS:
- violation of hemocoagulation;
- diseases of the liver, spleen and kidneys;
- Varicose veins;
- diseases of the cardiovascular system;
- autoimmune pathologies.
Also, side effects include less dangerous conditions, such as nausea, vomiting, loss of appetite, loose stools, and bloating. Sometimes skin manifestations in the form of itching and a small rash are also fixed.
Application on the example of the main drugs of the NSAID group
Consider the most popular and effective medicines.
| A drug | Route of administration into the body (form of release) and dosage | Application note | |||||
| outdoor | through the gastrointestinal tract | injection | |||||
| ointment | gel | tablets | candles | Injection in / m | Intravenous administration | ||
| Diclofenac (Voltaren) | 1-3 times (2-4 grams per affected area) per day | 20-25 mg 2-3 times a day | 50-100 mg once a day | 25-75 mg (2 ml) 2 times a day | — | Tablets should be taken without chewing, 30 minutes before meals, with plenty of water. | |
| Ibuprofen (Nurofen) | Strip 5-10 cm, rub 3 times a day | Strip of gel (4-10 cm) 3 times a day | 1 tab. (200 ml) 3-4 times a day | For children from 3 to 24 months. (60 mg) 3-4 times a day | — | 2 ml 2-3 times a day | For children, the drug is prescribed if the body weight exceeds 20 kg |
| Indomethacin | 4-5 cm ointment 2-3 times a day | 3-4 times a day, (strip - 4-5 cm) | 100-125 mg 3 times a day | 25-50 mg 2-3 times a day | 30 mg - 1 ml of solution 1-2 r. per day | 60 mg - 2 ml 1-2 times a day | During pregnancy, indomethacin is used to reduce uterine tone to prevent premature birth. |
| Ketoprofen | Strip 5 cm 3 times a day | 3-5 cm 2-3 times a day | 150-200 mg (1 tab.) 2-3 times a day | 100-160 mg (1 suppository) 2 times a day | 100 mg 1-2 times a day | 100-200 mg dissolved in 100-500 ml of saline | Most often, the drug is prescribed for pain of the musculoskeletal system. |
| Ketorolac | 1-2 cm of gel or ointment - 3-4 times a day | 10 mg 4 times a day | 100 mg (1 suppository) 1-2 times a day | 0.3-1 ml every 6 hours | 0.3-1 ml bolus 4-6 times a day | Taking the drug may mask signs of an acute infectious disease | |
| Lornoxicam (Xefocam) | — | — | 4 mg 2-3 times a day or 8 mg 2 times a day | — | Initial dose - 16 mg, maintenance - 8 mg - 2 times a day | The drug is used for pain syndrome of moderate and high severity | |
| Meloxicam (Amelotex) | — | 4 cm (2 grams) 2-3 times a day | 7.5-15 mg 1-2 times a day | 0.015 g 1-2 times a day | 10-15 mg 1-2 times a day | — | In renal failure, the allowable daily dose is 7.5 mg |
| Piroxicam | 2-4 cm 3-4 times a day | 10-30 mg 1 time per day | 20-40 mg 1-2 times a day | 1-2 ml once a day | — | The maximum allowable daily dosage is 40 mg | |
| Celecoxib (Celebrex) | — | — | 200 mg 2 times a day | — | — | — | The drug is available only in the form of coated capsules that dissolve in the gastrointestinal tract |
| Aspirin (acetylsalicylic acid) | — | — | 0.5-1 gram, take no more than 4 hours and no more than 3 tablets per day | — | — | — | If there have been allergic reactions to Penicillin in the past, then Aspirin should be prescribed with caution. |
| Analgin | — | — | 250-500 mg (0.5-1 tab.) 2-3 times a day | 250 - 500 mg (1-2 ml) 3 times a day | Analgin in some cases may have drug incompatibility, so it is not recommended to mix it in a syringe with other medicines. It is also banned in some countries. | ||
Attention! The tables show dosages for adults and adolescents whose body weight exceeds 50-50 kg. Many drugs for children under 12 years of age are contraindicated. In other cases, the dosage is selected individually, taking into account body weight and age.
In order for the drug to act as soon as possible and not cause harm to health, one should adhere to the well-known rules:
- Ointments and gels are applied to the painful area, then rubbed into the skin. Before putting on clothes, it is worth waiting for complete absorption. It is also not recommended to take water procedures for several hours after treatment.
- Tablets must be taken strictly as directed, not exceeding the daily allowable rate. If the pain or inflammation is too pronounced, then it is worth informing the attending physician about this in order to select another, stronger drug.
- Capsules should be washed down with plenty of water without removing the protective shell.
- Rectal suppositories act faster than tablets. Absorption of the active substance occurs through the intestines, so there is no negative and irritating effect on the walls of the stomach. If the drug is prescribed for a baby, then the young patient should be laid on his left side, then gently insert the candle into the anus and tightly clamp the buttocks. Within ten minutes, make sure that the rectal medication does not come out.
- Intramuscular and intravenous injections are given only medical worker! It is necessary to make injections in the manipulation room of a medical institution.
Despite the fact that non-steroidal anti-inflammatory drugs are available without a prescription, you should definitely consult your doctor before taking them. The fact is that the action of this group of medicines is not aimed at treating the disease, at relieving pain and discomfort. Thus, the pathology begins to progress and it is much more difficult to stop its development upon detection than it would have been done before.
Non-steroidal anti-inflammatory drugs, which are briefly called NSAIDs or NSAIDs (means) are widely used throughout the world. In the United States, where statistics cover all branches of life, it was estimated that every year American doctors write more than 70 million prescriptions for NSAIDs. Americans drink, inject, and smear more than 30 billion doses of non-steroidal anti-inflammatory drugs a year. It is unlikely that our compatriots are lagging behind them.
Despite their popularity, most NSAIDs are distinguished by high safety and extremely low toxicity. Even when used in high doses, complications are extremely unlikely. What are these miraculous remedies?
Non-steroidal anti-inflammatory drugs are a large group of drugs that have three effects at once:
- painkillers;
- antipyretic;
- anti-inflammatory.
The term "non-steroidal" distinguishes these drugs from steroids, i.e. hormonal drugs, which also have anti-inflammatory effects.
The property that favorably distinguishes NSAIDs from other analgesics is the absence of addiction with prolonged use.
Excursion into history
The "roots" of non-steroidal anti-inflammatory drugs go back to the distant past. Hippocrates, who lived in 460-377. BC, reported the use of willow bark for pain relief. A little later, in the 30s BC. Celsius confirmed his words and stated that willow bark perfectly softens the signs of inflammation.
The next mention of the analgesic cortex is found only in 1763. And only in 1827, chemists were able to isolate from the willow extract the very substance that became famous in the time of Hippocrates. The active ingredient in willow bark turned out to be the glycoside salicin, a precursor to non-steroidal anti-inflammatory drugs. From 1.5 kg of bark, scientists received 30 g of purified salicin.
In 1869, for the first time, a more effective derivative of salicin, salicylic acid, was obtained. It soon became clear that it damages the gastric mucosa, and scientists began an active search for new substances. In 1897, the German chemist Felix Hoffmann and the Bayer company ushered in a new era in pharmacology by converting the toxic salicylic acid into acetylsalicylic acid, which was named Aspirin.
For a long time, aspirin remained the first and only representative of the NSAID group. Since 1950, pharmacologists began to synthesize more and more new drugs, each of which was more effective and safer than the previous one.
How do NSAIDs work?
Non-steroidal anti-inflammatory drugs block the production of substances called prostaglandins. They are directly involved in the development of pain, inflammation, fever, muscle cramps. Most NSAIDs non-selectively (non-selectively) block two different enzymes that are required for prostaglandin production. They are called cyclooxygenase - COX-1 and COX-2.
The anti-inflammatory effect of non-steroidal anti-inflammatory drugs is largely due to:
- a decrease in vascular permeability and an improvement in microcirculation in them;
- a decrease in the release from cells of special substances that stimulate inflammation - inflammatory mediators.
In addition, NSAIDs block energy processes in the focus of inflammation, thereby depriving it of "fuel". Analgesic (pain-relieving) action develops as a result of a decrease in the inflammatory process.
Serious disadvantage
It's time to talk about one of the most serious disadvantages of non-steroidal anti-inflammatory drugs. The fact is that COX-1, in addition to participating in the production of harmful prostaglandins, also plays positive role. It is involved in the synthesis of prostaglandin, which prevents the destruction of the gastric mucosa under the action of its own hydrochloric acid. When non-selective COX-1 and COX-2 inhibitors begin to work, they completely block prostaglandins - both "harmful" ones that cause inflammation and "beneficial" ones that protect the stomach. So non-steroidal anti-inflammatory drugs provoke the development of gastric and duodenal ulcers, as well as internal bleeding.
But there are special drugs among the NSAID family. These are the most modern tablets that can selectively block COX-2. Cyclooxygenase type 2 is an enzyme that is involved only in inflammation and does not carry any additional load. Therefore, blocking it is not fraught with unpleasant consequences. Selective COX-2 blockers do not cause gastrointestinal problems and are safer than their predecessors.
Nonsteroidal anti-inflammatory drugs and fever
NSAIDs have completely unique property which distinguishes them from other drugs. They have an antipyretic effect and can be used to treat fever. To understand how they work in this capacity, you should remember why the body temperature rises.
Fever develops due to an increase in the level of prostaglandin E2, which changes the so-called firing rate of neurons (activity) within the hypothalamus. Namely, the hypothalamus - a small area in the diencephalon - controls thermoregulation.
Antipyretic non-steroidal anti-inflammatory drugs, also called antipyretics, inhibit the COX enzyme. This leads to inhibition of prostaglandin production, which as a result contributes to the inhibition of neuronal activity in the hypothalamus.
By the way, it was found that ibuprofen has the most pronounced antipyretic properties. It outperformed its closest competitor, paracetamol, in this respect.
Classification of non-steroidal anti-inflammatory drugs
And now let's try to figure out what kind of drugs belong to non-steroidal anti-inflammatory drugs.
Today, several dozen drugs of this group are known, but far from all of them are registered and used in Russia. We will consider only those medicines that can be bought in domestic pharmacies. NSAIDs are classified according to their chemical structure and mechanism of action. In order not to frighten the reader with complex terms, we present a simplified version of the classification, in which we present only the most famous names.
So, the entire list of non-steroidal anti-inflammatory drugs is divided into several subgroups.
Salicylates
The most experienced group, with which the history of NSAIDs began. The only salicylate that is still used today is acetylsalicylic acid, or Aspirin.
Propionic acid derivatives
These include some of the most popular non-steroidal anti-inflammatory drugs, in particular drugs:
- ibuprofen;
- naproxen;
- ketoprofen and some other medicines.
Acetic acid derivatives
Acetic acid derivatives are no less famous: indomethacin, ketorolac, diclofenac, aceclofenac and others.
Selective COX-2 inhibitors
The safest non-steroidal anti-inflammatory drugs include seven new drugs of the latest generation, but only two of them are registered in Russia. Memorize them international titles are celecoxib and rofecoxib.
Other non-steroidal anti-inflammatory
Separate subgroups include piroxicam, meloxicam, mefenamic acid, nimesulide.
Paracetamol has very weak anti-inflammatory activity. It mainly blocks COX-2 in the central nervous system and has an analgesic, as well as a moderate antipyretic effect.
When are NSAIDs used?
Typically, NSAIDs are used to treat acute or chronic inflammation accompanied by pain.
We list the diseases in which non-steroidal anti-inflammatory drugs are used:
- arthrosis;
- moderate pain due to inflammation or soft tissue injury;
- osteochondrosis;
- lower back pain;
- headache;
- migraine;
- acute gout;
- dysmenorrhea (menstrual pain);
- bone pain caused by metastases;
- postoperative pain;
- pain in Parkinson's disease;
- fever (increased body temperature);
- intestinal obstruction;
- renal colic.
In addition, non-steroidal anti-inflammatory drugs are used to treat children whose ductus arteriosus does not close within 24 hours of birth.
This amazing aspirin!
Aspirin can be safely attributed to the drugs that surprised the whole world. The most common non-steroidal anti-inflammatory pills that have been used to reduce fever and treat migraine have shown an unusual side effect. It turned out that by blocking COX-1, aspirin at the same time inhibits the synthesis of thromboxane A2, a substance that increases blood clotting. Some scientists suggest that there are other mechanisms for the effect of aspirin on blood viscosity. However, for millions of patients with hypertension, angina pectoris, coronary heart disease and other cardiovascular diseases, this is not so significant. For them, it is much more important that aspirin in low doses helps prevent cardiovascular disasters - heart attack and stroke.
Most experts recommend taking low-dose cardiac aspirin to prevent myocardial infarction and stroke in men aged 45–79 and women aged 55–79. The dose of aspirin is usually prescribed by a doctor: as a rule, it ranges from 100 to 300 mg per day.
A few years ago, scientists discovered that aspirin reduces the overall risk of developing cancer and mortality from them. This effect is especially true for rectal cancer. American doctors recommend that their patients take aspirin specifically to prevent the development of colorectal cancer. In their opinion, the risk of side effects due to long-term treatment with aspirin is still lower than oncological. By the way, let's take a closer look at the side effects of non-steroidal anti-inflammatory drugs.
Cardiac risks of non-steroidal anti-inflammatory drugs
Aspirin, with its antiplatelet effect, stands out from the orderly row of fellows in the group. The vast majority of non-steroidal anti-inflammatory drugs, including modern COX-2 inhibitors, increase the risk of myocardial infarction and stroke. Cardiologists warn that patients who have recently experienced a heart attack should stop taking NSAIDs. According to statistics, the use of these drugs almost 10 times increases the likelihood of developing unstable angina. According to research data, naproxen is considered the least dangerous from this point of view.
On July 9, 2015, the FDA, the most authoritative American drug quality control organization, issued an official warning. It talks about an increased risk of stroke and heart attack in patients using non-steroidal anti-inflammatory drugs. Of course, aspirin is a happy exception to this axiom.
The effect of non-steroidal anti-inflammatory drugs on the stomach
Another known side effect of NSAIDs is gastrointestinal. We have already said that it is closely related to the pharmacological action of all non-selective inhibitors of COX-1 and COX-2. However, NSAIDs not only reduce prostaglandin levels and thereby deprive the gastric mucosa of protection. Drug molecules themselves behave aggressively towards the mucous membranes of the gastrointestinal tract.
Against the background of treatment with non-steroidal anti-inflammatory drugs, nausea, vomiting, dyspepsia, diarrhea, stomach ulcers, including those accompanied by bleeding, may occur. Gastrointestinal side effects of NSAIDs develop regardless of how the drug enters the body: oral in the form of tablets, injections in the form of injections or rectal suppositories.
The longer the treatment lasts and the higher the dosage of NSAIDs, the higher the risk of developing peptic ulcer. To minimize the likelihood of it occurring, it makes sense to take the lowest effective dose for the shortest period.
Recent studies show that more than 50% of people taking non-steroidal anti-inflammatory drugs, the lining of the small intestine is still damaged.
Scientists note that drugs of the NSAID group affect the gastric mucosa in different ways. So, the most dangerous drugs for the stomach and intestines are indomethacin, ketoprofen and piroxicam. And among the most harmless in this regard are ibuprofen and diclofenac.
Separately, I would like to say about enteric coatings that cover non-steroidal anti-inflammatory tablets. Manufacturers claim that this coating helps to reduce or completely eliminate the risk of gastrointestinal complications of NSAIDs. However, research and clinical practice show that such protection does not actually work. Much more effectively, the likelihood of damage to the gastric mucosa reduces the simultaneous use of drugs that block the production of hydrochloric acid. Proton pump inhibitors - omeprazole, lansoprazole, esomeprazole and others - can somewhat mitigate the damaging effect of drugs from the group of non-steroidal anti-inflammatory drugs.
Say a word about citramone ...
Citramon is the product of a brainstorming session of Soviet pharmacologists. In ancient times, when the assortment of our pharmacies did not number in the thousands of drugs, pharmacists came up with an excellent formula for analgesic-antipyretic. They combined "in one bottle" a complex of a non-steroidal anti-inflammatory drug, an antipyretic and seasoned the combination with caffeine.
The invention turned out to be very successful. Each active ingredient enhanced the effect of each other. Modern pharmacists have somewhat modified the traditional prescription, replacing the antipyretic phenacetin with safer paracetamol. In addition, cocoa and citric acid, which, in fact, gave the name to citramone, were removed from the old version of citramone. The preparation of the XXI century contains aspirin 0.24 g, paracetamol 0.18 g and caffeine 0.03 g. And despite a slightly modified composition, it still helps with pain.
However, despite the extremely affordable price and very high efficiency, Citramon has its own huge skeleton in the closet. Doctors have long found out and fully proved that it seriously damages the mucosa of the gastrointestinal tract. So seriously that the term "citramone ulcer" even appeared in the literature.
The reason for this apparent aggression is simple: the damaging effect of Aspirin is enhanced by the activity of caffeine, which stimulates the production of hydrochloric acid. As a result, the gastric mucosa, already left without protection of prostaglandins, is exposed to the action of an additional amount of hydrochloric acid. Moreover, it is produced not only in response to food intake, as it should be, but also immediately after the absorption of Citramon into the blood.
We add that "citramone", or as they are sometimes called, "aspirin ulcers" are large. Sometimes they do not "grow" to gigantic, but they take in quantity, settling in whole groups in different parts of the stomach.
The moral of this digression is simple: don't go overboard with Citramon despite all its benefits. The consequences can be too severe.
NSAIDs and… sex
In 2005, in the piggy bank of unpleasant side effects of non-steroidal anti-inflammatory drugs arrived. Finnish scientists conducted a study that showed that long-term use of NSAIDs (over 3 months) increases the risk of erectile dysfunction. Recall that under this term, doctors mean erectile dysfunction, popularly called impotence. Then urologists and andrologists were not very comforted high quality of this experiment: the effect of drugs on sexual function was evaluated only on the basis of the man's personal feelings and was not verified by specialists.
However, in 2011, another study was published in the authoritative Journal of Urology. It also showed an association between treatment with non-steroidal anti-inflammatory drugs and erectile dysfunction. However, doctors argue that it is too early to draw final conclusions regarding the effect of NSAIDs on sexual function. In the meantime, scientists are looking for evidence, it is still better for men to refrain from long-term treatment with non-steroidal anti-inflammatory drugs.
Other side effects of NSAIDs
With the serious troubles that threaten treatment with non-steroidal anti-inflammatory drugs, we figured it out. Let's move on to less common adverse events.
Impaired kidney function
The use of NSAIDs is also associated with a relatively high level of renal side effects. Prostaglandins are involved in the expansion of blood vessels in the renal glomeruli, which allows you to maintain normal filtration in the kidneys. When the level of prostaglandins falls - and it is on this effect that the action of non-steroidal anti-inflammatory drugs is based - the work of the kidneys may be disturbed.
People with kidney disease are, of course, most at risk for kidney side effects.
photosensitivity
Quite often, long-term treatment with non-steroidal anti-inflammatory drugs is accompanied by increased photosensitivity. It is noted that piroxicam and diclofenac are more involved in this side effect.
People taking anti-inflammatory drugs may react to the sun's rays with skin redness, rashes, or other skin reactions.
Hypersensitivity reactions
Non-steroidal anti-inflammatory drugs are also "famous" for allergic reactions. They can manifest as a rash, photosensitivity, itching, Quincke's edema, and even anaphylactic shock. True, the latter effect is among the extremely rare and therefore should not frighten potential patients.
In addition, taking NSAIDs may be accompanied by headache, dizziness, drowsiness, bronchospasm. Rarely, ibuprofen causes irritable bowel syndrome.
Non-steroidal anti-inflammatory during pregnancy
Quite often, pregnant women face the issue of anesthesia. Can expectant mothers use NSAIDs? Unfortunately no.
Despite the fact that non-steroidal anti-inflammatory drugs do not have a teratogenic effect, that is, they do not cause gross malformations in a child, they can still do harm.
So, there is evidence that suggests a possible premature closure of the ductus arteriosus in the fetus if his mother took NSAIDs during pregnancy. In addition, some studies show an association between NSAID use and preterm birth.
Nevertheless, selected drugs are still used during pregnancy. For example, Aspirin is often given with heparin to women who have antiphospholipid antibodies during pregnancy. Recently, the old and rather rarely used Indomethacin has gained particular fame as a medicine for the treatment of pregnancy pathologies. It began to be used in obstetrics for polyhydramnios and the threat of premature birth. However, in France, the Ministry of Health issued an official order banning the use of non-steroidal anti-inflammatory drugs, including aspirin, after the sixth month of pregnancy.
NSAIDs: accept or refuse?
When do NSAIDs become a necessity, and when should they be abandoned outright? Let's look at all possible situations.
| NSAIDs needed | Take NSAIDs with caution | Better to avoid NSAIDs |
| If you have osteoarthritis that is accompanied by pain, inflammation of the joints and impaired mobility that is not relieved by other drugs or paracetamol If you have rheumatoid arthritis with severe pain and inflammation If you have a moderate headache, joint or muscle injury (NSAIDs are prescribed only for a short time. It is possible to start pain relief with paracetamol) If you have mild chronic pain that is not related to osteoarthritis, such as in your back. |
If you often suffer from indigestion If you are over 50 years of age or have a history of gastrointestinal disease and/or a family history of early heart disease If you smoke, have high level cholesterol or high blood pressure or suffer from kidney disease if you are taking steroids or blood thinners (clopidogrel, warfarin) If you are forced to take NSAIDs to relieve symptoms of osteoarthritis for many years, especially if you have had gastrointestinal diseases |
if you have ever had a stomach ulcer or stomach bleeding If you suffer from coronary artery disease or any other heart disease If you suffer from severe hypertension If you have chronic kidney disease If you have ever had a myocardial infarction If you are taking aspirin to prevent a heart attack or stroke If you are pregnant (especially in the third trimester) |
NSAIDs in faces
We already know the strengths and weaknesses of NSAIDs. And now let's figure out which anti-inflammatory drugs are best used for pain, which ones for inflammation, and which ones for fever and colds.
Acetylsalicylic acid
The first NSAID to be released, acetylsalicylic acid, is still widely used today. As a rule, it is used:
- to lower body temperature.
Please note that acetylsalicylic acid is not prescribed to children under the age of 15 years. This is due to the fact that with childhood fever against the background of viral diseases, the drug significantly increases the risk of developing Reye's syndrome, a rare liver disease that poses a threat to life.
The adult dosage of acetylsalicylic acid as an antipyretic is 500 mg. Tablets are taken only when the temperature rises.
- as an antiplatelet agent for the prevention of cardiovascular accidents. The dose of cardioaspirin can range from 75 mg to 300 mg per day.
In an antipyretic dosage, acetylsalicylic acid can be bought under the names Aspirin (manufacturer and owner trademark German corporation Bayer). Domestic enterprises produce very inexpensive tablets, which are called Acetylsalicylic acid. In addition, the French company Bristol Myers produces Upsarin Upsa effervescent tablets.
Cardioaspirin has many names and formulations, including Aspirin Cardio, Aspinat, Aspicor, CardiASK, Thrombo ACC, and others.
ibuprofen
Ibuprofen combines relative safety and the ability to effectively reduce fever and pain, so preparations based on it are sold without a prescription. As an antipyretic, ibuprofen is also used for newborns. It has been proven to reduce fever better than other non-steroidal anti-inflammatory drugs.
In addition, ibuprofen is one of the most popular over-the-counter analgesics. As an anti-inflammatory agent, it is not prescribed so often, however, the drug is quite popular in rheumatology: it is used to treat rheumatoid arthritis, osteoarthritis and other joint diseases.
The most popular brand names for ibuprofen include Ibuprom, Nurofen, MIG 200 and MIG 400.
Naproxen
Naproxen is prohibited for use in children and adolescents under 16 years of age, as well as in adults suffering from severe heart failure. Most often, non-steroidal anti-inflammatory drugs naproxen are used as painkillers for headache, dental, periodic, joint and other types of pain.
In Russian pharmacies, naproxen is sold under the names Nalgezin, Naprobene, Pronaxen, Sanaprox and others.
Ketoprofen
Ketoprofen preparations are distinguished by anti-inflammatory activity. It is widely used to relieve pain and reduce inflammation in rheumatic diseases. Ketoprofen is available in the form of tablets, ointments, suppositories and injections. Popular drugs include the Ketonal line manufactured by the Slovak company Lek. German joint gel Fastum is also famous.
Indomethacin
One of the outdated non-steroidal anti-inflammatory drugs, Indomethacin is losing ground every day. It has modest analgesic properties and moderate anti-inflammatory activity. AT last years Increasingly, the name "indomethacin" sounds in obstetrics - its ability to relax the muscles of the uterus has been proven.
Ketorolac
A unique non-steroidal anti-inflammatory drug with a pronounced analgesic effect. The analgesic abilities of ketorolac are comparable to those of some weak narcotic analgesics. The negative side of the drug is its insecurity: it can cause stomach bleeding, provoke stomach ulcers, and liver failure. Therefore, you can use ketorolac for a limited period of time.
In pharmacies, Ketorolac is sold under the names Ketanov, Ketalgin, Ketorol, Toradol and others.
diclofenac
Diclofenac is the most popular non-steroidal anti-inflammatory drug, the "gold standard" in the treatment of osteoarthritis, rheumatism and other joint pathologies. It has excellent anti-inflammatory and analgesic properties and is therefore widely used in rheumatology.
Diclofenac has many forms of release: tablets, capsules, ointments, gels, suppositories, ampoules. In addition, diclofenac patches have been developed to provide a long-lasting effect.
There are a lot of analogues of diclofenac, and we will list only the most famous of them:
- Voltaren is the original drug of the Swiss company Novartis. Differs in high quality and the same high price;
- Diklak - a line of German drugs from Heksal, combining both reasonable cost and decent quality;
- Dicloberl made in Germany, Berlin Chemie company;
- Naklofen - Slovak drugs from KRKA.
In addition, the domestic industry produces many inexpensive non-steroidal anti-inflammatory drugs with diclofenac in the form of tablets, ointments and injections.
Celecoxib
A modern non-steroidal inflammatory drug that selectively blocks COX-2. It has a high safety profile and pronounced anti-inflammatory activity. It is used for rheumatoid arthritis and other joint diseases.
The original celecoxib is sold under the name Celebrex (Pfizer). In addition, pharmacies have more affordable Dilaxa, Coxib and Celecoxib.
Meloxicam
A popular NSAID used in rheumatology. It has a rather mild effect on the digestive tract, so it is often preferred for the treatment of patients with a history of diseases of the stomach or intestines.
Assign meloxicam in tablets or injections. Meloxicam preparations Melbek, Melox, Meloflam, Movalis, Exen-Sanovel and others.
Nimesulide
Most often, nimesulide is used as a mild analgesic, and sometimes as an antipyretic. Until recently, pharmacies sold a children's form of nimesulide, which was used to reduce fever, but today it is strictly prohibited for children under 12 years of age.
Trade names of nimesulide: Aponil, Nise, Nimesil (German original drug in the form of a powder for preparing a solution for internal use) and others.
Finally, we will devote a couple of lines to Mefenamic acid. It is sometimes used as an antipyretic, but it is significantly inferior in effectiveness to other non-steroidal anti-inflammatory drugs.
The world of NSAIDs is truly amazing in its diversity. And despite the side effects, these drugs are rightfully among the most important and necessary, which can neither be replaced nor bypassed. It remains only to give praise to the tireless pharmacists who continue to create new formulas, and to be treated with ever safer NSAIDs.
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. It is 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 heart failure, the period after coronary artery bypass grafting, progressive kidney disease, active liver disease, pregnancy, 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 in 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. Due to the large number of contraindications and side effects, it 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.
In the 19th century, the business world of the country changed significantly. The reforms were the reason for the success of representatives of the estates, previously limited in the right to conduct entrepreneurial activity. This is the time of the rise of the Vtorov, Morozov, Vogau, Ryabushinsky dynasties, the formation of the business of talented engineers N.I. Putilov and N.S. Avdakov, the heyday of others famous families. Implementing their projects, they did not disregard either the interests of the state or the needs of the people.
The 19th century occupies a special place in the history of Russian business. The state conducts legislative activities, trying to create favorable conditions for the development of the economy. By the end of the century, the system of guilds, established in the time of Peter the Great to systematize and regulate business activities, protect the rights of merchants and create class privileges, had exhausted itself.
The reform of trade taxation in 1898 fixed the enterprise as the object of taxation, and not the personality of the entrepreneur, as it was before. Increasing competition in trade has caused business people to turn to industrial production. Transformations in the field of joint-stock business established the limitation of liability and provided an opportunity for representatives of different classes to participate in commercial enterprises.
The changes led to the fact that business circles were replenished with people from peasants, philistines, nobles, foreigners and employees. Due big business by the beginning of the 20th century, about 1.5 million people lived in the country.
The names of well-known entrepreneurs of Russia of the 19th century are well known today: the representatives of the families are famous for the introduction of advanced technologies, charity, participation in political life.
Morozov
Savva Vasilyevich Morozov (1770 - 1860) - the founder of the dynasty - comes from the serfs of the village of Zuyevo, Bogorodsky district, Moscow province. He achieved his success thanks to his personal qualities: diligence and business acumen. Having started work as a weaver in a factory, after his marriage, he organized a small production where he himself worked with his wife and sons. Savva sold silk fabrics and openwork ribbons created in the workshop in Moscow. The income allowed the entrepreneur and his family to buy out from the landowner in 1820. Savva's family had five sons: Elisha, Zakhar, Abram, Ivan and Timothy. An entrepreneurial streak is characteristic of many of Savva's descendants: the family is considered to consist of several branches, whose representatives became known in the textile business and other areas. In 1842, the Morozovs received hereditary honorary citizenship, which eliminated the restrictions imposed on peasants and urban dwellers.
Over time, the Morozovs bought land, built new factories for the production of silk, woolen and cotton fabrics, introducing into production modern technologies and mechanisms.
The first of Savva Vasilievich's enterprises grew into the Partnership of the Nikolskaya Manufactory "Savva Morozov's son and Co." pleated production.
The name of the manufactory is associated with the "Morozov strike" of 1885 in the village. Nikolsky. Workers protested against low wages and high fines for violations. The speech was suppressed, some of the participants were arrested by the authorities, but the event had positive consequences for the workers. Under the leadership of Savva Timofeevich, new English equipment was installed, working conditions and the life of workers were improved.
The company of the Bogorodsko-Glukhovskaya manufactory was founded in 1830 and transferred by Savva Vasilyevich to his son Zakhar, who gave life to the Zakharovichi branch. The enterprise became the first enterprise in the form of a partnership in central area countries. It included spinning, weaving, dyeing, bleaching, thread production and peat extraction.
The eldest son of Savva Morozov, Elisey, having separated himself, organized his own manufactory, which later acquired the name "The Association of Manufactories of Morozov Vikula with Sons." Vikula Eliseevich played an important role in the development of the enterprise and took over the reins of government from his retired father. This branch of the Morozov family is named after him - "Vikulovichi".
Under the control of the "Tver" Morozovs - the descendants of Abram - there was an enterprise created by Timofey at the request of his father. The Tver manufactory produced about thirty types of cotton fabrics, which were in constant demand at Russian fairs, and were also exported. Abram and David Abramovich led the production.
Social infrastructure grew up around Morozov's enterprises: shops, baths, hospitals, schools, almshouses, stadiums. The legacy of the dynasty of manufacturers can still be seen today on the streets of Orekhov-Zuev, Noginsk, Zheleznodorozhny and other settlements near the capital.
Researchers note various reasons for the success of the dynasty's ventures, including:
- active entrepreneurial position;
- striving for the mechanization of labor, stake on a high technical level of production;
- continuous modernization of production facilities;
- rejection foreign specialists and support for domestic education and recruitment of graduates of Russian educational institutions;
- creation of laboratories to combine theoretical and experimental science with production;
- a two-stage management model that eliminated the exclusive authoritarian influence of owners through the involvement of qualified hired management personnel;
- gradual awareness of social responsibility to the personnel of enterprises.
In addition to textile production, the family participated in the activities of other institutions. Timofei Morozov was one of the founders of the Volga-Kama Bank, established in 1870 and holding a leading position in the country until the end of the century. In the period 1868-76, he also served as chairman of the Moscow Exchange Committee, which cooperated with the state in matters of legislative activity in the field of trade and industry, regulated exchange trading, issued certificates and conclusions on commercial affairs. David Ivanovich built a railway line away from the main line Moscow - Vladimir, ending with the station "Zakharovo", named after his grandfather and still existing.
Representatives of the family did a lot of charity work and supported the culture of the country. With the financing of the Morozovs, the Alekseevskaya psychiatric hospital, the Morozovskaya children's hospital, the Cancer Institute and other medical institutions were built. With the participation of the Moscow Merchant Society of Mutual Credit, whose founders included T.S. Morozov, financed the newspapers "Moskvich" and "Shareholder", the magazine "Bulletin of Industry". Varvara Alekseevna, the wife of Abram Abramovich, donated funds to set up a free Turgenev library-reading room in 1895, supported the Russkiye Vedomosti newspaper, and took part in creating the technical base of many educational institutions, for example, the Imperial Technical School. Sergei Timofeevich provided assistance to the artist Levitan, Savva Timofeevich did not leave the Moscow Art Theater without the support. In a word, in pre-revolutionary Moscow it was difficult to find a charity event or social institution, which remained outside the attention and support of the Morozovs.
At the beginning of the 20th century, the fortune of the Morozov family, according to Forbes magazine, was in the modern equivalent of over 500 million dollars, which puts them in fourth place in the list of the richest Russian entrepreneurs of their time.
On the eve of the October Revolution, according to historians, about 60 families of the descendants of Savva Vasilyevich lived in Moscow. After October 1917, the life of the Morozovs developed in different ways: some immigrated (Nikolai Davidovich, Sergei Timofeevich, Pyotr Arsenievich and others), but the majority remained in their homeland, where a time of trials and losses awaited them.
Ryabushinsky
The founder of the dynasty is the peasant Mikhail Yakovlev, who in 1802 arrived in Moscow from the Kaluga province, acquired a shop and joined the merchants of the third guild. Subsequently, the family surname was changed according to the name of the founder's native settlement. The interests of the entrepreneur lay in the field of the textile industry: in 1846 he acquired the first weaving production. The middle son, Pavel Mikhailovich, brought the family business of the Ryabushinskys to the wide road, who sold the old father's manufactories and acquired the factory, equipping it with the latest technology.
In 1887, the family business was transformed into the "P. M. Ryabushinsky Manufactory Partnership", the fixed capital of which amounted to 2 million rubles. The company owned a paper-spinning, weaving, dyeing, finishing, and finishing factories in the Tver province. By the beginning of the 20th century, the capital of the enterprise had grown to 5 million rubles; in general, the family's fortune was estimated at over 20 million rubles.
After the death of Pavel and his wife, the business was headed by their eldest son, Pavel Pavlovich, whose name is more often associated with social and political activities, however, it was under his leadership that the Ryabushinsky business continued to flourish at the turn of the century. Pavel, like his brothers, was educated at the Moscow Practical Academy of Commercial Sciences - an institution of secondary education for the training of businessmen, which is under the jurisdiction of the Ministry of Finance. Four of the eight brothers worked with Pavel: Sergey, Vladimir, Stepan and Mikhail. Entrepreneurs established themselves in the linen industry, invested in sawmilling, and were engaged in paper production.
The family owned the "Banking House of the Ryabushinsky Brothers", which was later transformed into the Moscow Bank with the support of entrepreneurs employed textile industry. The Ryabushinskys recruited graduates of the academy where Pavel studied; village children were trained for the positions of junior staff, who, in addition to school, were trained at the expense of entrepreneurs in trading evening classes.
The well-known plans of the Ryabushinskys characterize the brothers as far-sighted entrepreneurs who relied on investments in promising technologies.
So, during the First World War, Sergei and Stepan established the Moscow Association of the Automobile Plant - an enterprise that, in Soviet time was converted to ZIL. A year after the laying, the plant was supposed to produce the first batch of trucks under the license of the Italian company FIAT. The equipment was created, although in violation of the deadlines, but the plant was not fully completed due to the events of 1917. The projects for oil exploration at the Ukhta fields and for the creation of machine-building enterprises in the Urals remained unrealized.
In the financial sector, the brothers' plan to create a "world-wide" bank is known through the merger of the Moscow Bank with other large institutions: the Volga-Kama and Russian commercial and industrial.
Pavel Pavlovich, in addition to managing family affairs, was passionate about socio-political processes, took an active part in the life of the country, consistently defending his position:
- collaborated with the "Union of October 17", with which he later broke off relations due to disagreement with the policy of P. Stolypin;
- published the newspapers "Morning", "Narodnaya Gazeta", "Morning of Russia", where he set out his vision of the prospects for the development of the state.
The entrepreneur saw the path of the country's development in combining the Old Believer traditions of pre-Petrine Russia with the institutions of Western capitalism, and warned the intelligentsia against being carried away by socialist ideas. Ryabushinsky fully supported the events of February 1917, because he believed that they opened up the opportunity for merchants and industrialists to influence the political life of the country.
After the revolution, the brothers emigrated, the descendants of the daughters of Pavel Mikhailovich live in Russia.
Vtorovs
Alexander Fedorovich Vtorov came from the Kostroma townspeople, lived in Irkutsk and, being a merchant, conducted wholesale trade in manufactured goods, furs, gold, and was engaged in financial transactions. Success in business allowed him to move to the 1st guild in 1876, and in 1897 to move with his family to Moscow and receive hereditary honorary citizenship. Alexander Alexandrovich remained to conduct business in Irkutsk, without stopping interaction with his father and brother. The elder Vtorov's brother, Pyotr Mazhukov, worked in Chita. Alexander Fedorovich successfully married off his daughters, becoming related to wealthy Moscow families.
Together with his son Nikolai, Alexander Fedorovich established an enterprise, which later became known as the “A.F. Vtorov and sons”, which:
- traded in textiles and tea;
- supplied raw materials for the production of smokeless powder to the treasury;
- owned commercial real estate in the cities of Siberia and the Urals;
- carried out manufactory production;
- conducted foreign trade operations in Mongolia.
Nikolai Aleksandrovich was distinguished by extraordinary thinking and chose promising industries and enterprises for investments, the effectiveness of which allowed him to increase his father's fortune.
At the end of the century, Nikolai Alexandrovich focused his interests on gold mining, but did not disregard other areas of activity: he expanded the list of textile enterprises, military uniforms and ammunition were made at his factories, he created the Moscow Industrial Bank, was engaged in the production of dyes, and worked in other industrial industries. Founded by the Second Partnership on Equity "Elektrostal" became the first such plant in Russia and gave birth to the city of the same name.
In the management of some enterprises, Nikolai Aleksandrovich was assisted by his son, Boris. The result of fruitful work was the largest fortune in the country, which surpassed the wealth of others famous families and was estimated at over 700 million modern dollars.
Nikolai Alexandrovich was killed in 1918, his family moved to France. Alexander Vtorov left Irkutsk in 1917.
Vogau
The founder of the business, Philipp-Max von Wogau, arrived in 1827 from Germany. Despite his noble origin, he was poor, was forced at first to serve "on parcels." Having no prospects in his homeland, he takes Russian citizenship and seeks a better life in Russia. The reputation earned here in 1839 gives Maxim Maksimovich the opportunity to marry the daughter of a textile manufacturer F. Rabenek. Since that time, the Vogau dynasty of Russian entrepreneurs has been counting down.
With the participation of the brothers Friedrich and Karl, Maxim Maksimovich opens an office that first sells tea, household and household chemicals, and then switched to the import of sugar, yarn and cotton. The enterprise grew into the trading house "Vogau and K", which until the October Revolution was under the control of the family. In addition to the brothers, their sons-in-law Erwin Schumacher and Konrad Banza, nephew Mark Moritz, Max's sons Otto and Hugo took part in the family business. The company reached its peak of development during the management of Hugo Maksimovich, the son of the founder of the dynasty.
In addition to conducting large-scale foreign trade operations, the family invested in the financial sector and industry:
- with the participation of Vogau, the Moscow Accounting Bank, the Russian Bank for Foreign Trade, the Riga Commercial Bank and the Yakor insurance company were created;
- the family controlled enterprises in various industries, the circle of interests included ore mining, metal smelting, cement production, chemical and textile production;
- together with Knop, they searched for deposits of platinum and oil in the Urals and copper in the Caucasus.
The way of life of the family was usual for the German bourgeois: they professed Lutheranism, lived in the neighborhood, preserved the traditions of their people. In 1900, five of the eight members of the board of the company remained German citizens, so with the outbreak of war, Wogau was in difficult situation. Part of the enterprises suffered from pogroms, government supervision was established over the activities of the company. The family was forced to sell the leading businesses.
Hugo took part in the financing of the founded P.P. Ryabushinsky of the newspaper "Morning of Russia", which criticized government policy in the economic sphere and was closed by the authorities "due to harmful direction".
The fortune of the Vogau family, acquired over 90 years in Russia, was comparable to the wealth of the Morozovs and, according to Forbs, amounted to about 500 million dollars in modern terms.
After 1917 most of the Wogau emigrated from Russia. Today, the descendants of Hugo's son, Maxim, who has been a member of the CPSU (b) since 1919, live in the country.
Entrepreneurial engineer N.S. Avdakov
Nikolai Stepanovich was born in 1847 in the family of a military doctor assigned to the Kurinsky regiment stationed in the Caucasus. Avdakov's ancestors lived in the Vladimir province and, for the most part, were clergymen. Nikolai was educated at the Petersburg Mining Institute, from which he graduated in 1873. The Main Mining Administration sent Avdakov to work as a mine engineer in the Rutchenko coal company, located in the Yekaterinoslav province and created with Belgian capital.
