Classification of the NSAID on anti-inflammatory activity. Clinical pharmacology of non-steroidal anti-inflammatory drugs: course -

Date: 27.07.2020

Non-steroidal anti-inflammatory funds (NSAIDs) occupy a leading position in the volume of consumption in the world, which is explained, first of all, high efficiency in painful syndrome of inflammatory origin.

The uniqueness of the NSAID as a class of drugs is due to the combination of anti-inflammatory, painkillers, antipyretic and antithrombotic action. Under the pains of moderate and high intensity, the analgesic effect of the NSAID is stronger than that of simple analgesics (paracetamol), and some preparations are in force with opiates.

Due to the large number of NSAIDs presented in the market in front of the therapist and neurologist, it is quite often a matter of rational choice of a particular drug under states accompanied by pain syndrome, especially in the pathology of the joints and the bone-muscular apparatus as a whole.

The choice of the drug should be carried out taking into account the risk of complications of pharmacotherapy and to be made in favor of funds with the most favorable portability.

Classification and mechanism of the operation of the NSAID

There are several NSAID classifications, the most difficult of which is the classification of a chemical structure reflecting the heterogeneity in the structure of the molecule of different NSAIDs.

In clinical practice, NSAIDs on the selectivity of exposure to cyclooxygenase (COW) is fundamental importance, which catalyzes one of the stages of the synthesis of prostaglandins and thereby responsible for the development of the inflammatory response.

The suppression of the COW leads to an increase in the disposal of arachidonic acid in the lipoxygenase path, that is, to the increased formation of leukotrienes, which narrow the vessels and limit the exudation.

In the human body there are two subspecies (isoenzyme) COG: COF-1 and COF-2.

COG-1 is present in almost all organs and is the isoenzyme that works not only under conditions of inflammation, but also in the absence of such, and provides normal physiological processes (synthesis of protective mucus of the stomach, some stages of blood formation, filtration and reabsorption in the kidneys). In the conditions of the pathology of COCH-1 participates in the development of inflammation.

COF-2 in high concentrations is found in the brain, bones, organs of the female sexual system, kidneys; Its synthesis is strongly activated under inflammation. It is believed that it is COG-2 that takes part in the synthesis of pro-inflammatory prostaglandins that potentiate the activity of inflammation mediators (histamine, serotonin, bradykinin), irritating pain receptors in the focus of inflammation involved in managing the activity of the center of thermal regulation, contributing to cell proliferation, mutagenesis and destruction.

The high activity of COF-2 was detected in epithelial cancer cells and atherosclerotic plaques, where the enzyme correspondively slows down the natural processes of apoptosis and contributes to atherogenesis.

The oppression of COF-1 and COG-2 under the influence of non-selective NSAIDs contributes to the development of side effects associated with the oppression of the physiological role of the CHA, primarily to gastropathy (erosions and ulcers of the stomach), which is especially relevant if necessary, regular and long-term reception of the NSAIDs (as a rule , with rheumatic diseases). That is why selective COF-2 - 2 - nimesulide inhibitors have been developed, celecoxib and others, which made it possible to significantly reduce the risk of such complications.

So, the suppression of the activity of COG gives an anti-inflammatory, analgesic and antipyretic effect. Antiagragerant effect is due to the ability of the NSAID to inject COF-1 in platelets, violating the formation of thromboxane A2. Altogether acetylsalicylic acid is used as an antiagregant in medical practice.

In some inhibitors of COG-2 (nimesulide, meloxicam, celecoxib) in clinical studies, an antitumor effect was revealed against polypotic formations of the colon, some anti-seaterosclerotic effect, as well as a favorable therapeutic effect in Alzheimer's disease, but the presented properties require further study.

The overwhelming majority of NSAIDs are weak organic acids, therefore absorbed in the acidic area of \u200b\u200bthe stomach. Table 3 provides the pharmacokinetic parameters of the most popular NSAIDs.

Most NSAIDs have a small amount of distribution and half-life, but the duration of the effect does not always depends on these parameters, since the key value has the ability to penetrate and accumulate in the focus of inflammation.

The short half-life reduces the risk of medication complications. The rate of occurrence of the effect as a whole depends on the pathness of those or other drugs to organs and tissues.

Thanks to the unique combination of pharmacological effects, the NSAIDs was widely used in medicine, the main testimony for the purpose is summarized in Table. four.

Adverse adverse reactions

Due to the considerable popularity of NSAIDs in clinical practice, as well as due to the high level of self-treatment of this group of drugs, the clinician must be remembered about the most frequent complications of the NSAID therapy.

The most common side reactions include damage to the mucous membrane of the gastrointestinal tract (erosion, ulcers), which occurs as a result of the oppression of the synthesis of protective mucus. In this regard, the risk of damage to the mucous membrane with digestive juices is increasing, primarily gastric.

NSAIDs can lead to the development of the so-called "Silent" ulcers, i.e., the ulcers occurring without typical pain syndrome due to the presence of analgesic activity among drugs. Such ulcers after a long asymptomatic existence can manifest with gastrointestinal bleeding.

The risk of "silent" ulcers is large in senior patients, therefore, in this group of patients, regular endoscopic control is required in this group of patients with prolonged intake of NSAIDs.

The following complication is "Aspirin Asthma" (Vidal syndrome) - a combination of attacks of choking with a gloomy, rhinitis and polypose of the nasal mucosa. Since the COF under the influence of the NSAID is inhibited, arachidonic acid is disposed of on the way of the formation of leukotrienes, which cause such a complication.

It should be noted that many NSAIDs (most often non-selective inhibitors of COW) are able to cause partial bronchokonstriction or bronchospasm, therefore patients with bronchial asthma or bronchospasm on the NSAIDs in history, these drugs are prescribed with great caution or not use them at all.

The non-selective NSAIDs block COF-1 in the kidneys, which leads to a violation of filtration and reabsorption, provokes water delay, electrolytes in the body and provokes the edema. Liquid delay It is dangerous in patients with arterial hypertension and chronic heart failure, so when applying the NSPIDs, they need more thorough control of hemodynamic parameters, and sometimes correction of doses of cardiological medicines. Some NSAIDs (for example, diclofenac) have pronounced nephrotoxicity.

Hemorrhagic syndrome Most often is observed when using acetylsalicylic acid, since the drug irreversibly inhibits platelet aggregation and has anticoagulant properties. Nevertheless, it must be remembered that with the joint appointment of NSAIDs and antithrombotic drugs, the risk of bleeding increases.

Hepatotoxic reactions (From a minor increase in the level of liver enzymes to more heavy forms) can be observed when applying drugs metabulating in the liver. Risk factors are alcohol abuse, the presence of liver diseases and a parallel reception of hepatotoxic drugs.

A severe complication is syndrome Rey.which is an acute toxic encephalopathy with a cerebral edema and fat degeneration of internal organs, first of all liver. At the same time, the phenomena of inflammatory brain disease are absent.

The side reaction occurs when acetylsalicylic acid is prescribed against a viral infection (flu, chickenpox, cortex). Symptoms can develop at any age, but in the overwhelming majority of cases, children under 15 years old suffer. The disease can stop at the initial stage, but most often aggregate to a precautious or comatose state.

The number of cases of Ray's syndrome in developed countries is very little due to the ban on the purpose of acetylsalicylic acid to children with a fever caused by influenza.

NSAIDs are able to reduce fertility and have a negative effect on the fetus, so their use in pregnant women and women planning pregnancy is undesirable.

Conclusion

NSAIDs have a unique combination of anti-inflammatory, analgesic, antipyretic and antithrombotic action, which allows to control the course of many diseases.

The success of pharmacotherapy largely depends on the knowledge of the features of the action of individual NSAIDs, which provides an individual approach when selecting the drug with a specific patient. These features primarily applies to the degree of penetration into tissues, which need to be influenced by pharmacologically, as well as portability profile, which is important for the prevention of the development of complications of therapy, especially from the gastrointestinal tract with long-term treatment.

N.V. Sturov, V.I. Kuznetsov

The most important mechanism of the NSAIDs is the ability to inhibit the COF - an enzyme that catalyzing the conversion of free polyunsaturated fatty acids (for example, arachidonovaya) in prostaglandins (GHG), as well as other eikosanoids - thromboxanes (TR2) and prostacyclin (PG-I2) (Fig. one). It has been proven that prostaglandins have versatile biological activity:

a) are mediators of inflammatory response: They accumulate in the focus of inflammation and cause local extension of vessels, edema, exudation, leukocyte migration and other effects (mainly PG-E2 and PG-I2);

b) sensitize receptors to pain mediators (histamine, bradykinin) and mechanical effects, lowering sensitivity threshold;

at) increase the sensitivity of the hypothalamic centers of thermoregulation to the action of endogenous pyrogens (interleukin-1, etc.) formed in the body under the influence of microbes, viruses, toxins (mainly PG-E2);

d) play an important physiological role in the protection of the mucous membrane of the gastrointestinal tract (increase in the secretion of mucus and lumps; maintaining the integrity of the endothelial cells inside the microcosuds of the mucous membrane, which contributes to maintaining blood flow in the mucous membrane; maintaining the integrity of granulocytes and, thus, the preservation of the structural integrity of the mucous membrane);

e) affect the kidney function: Called vase detection, support the renal blood flow and the speed of glomerular filtration, increase the release of renin, the release of sodium and water, participate in potassium homeostasis.

Fig.1. "Cascade" of arachidonic acid metabolic products and their main effects.

Note: * LT-C 4, D 4, E 4 are the main biological components of a slowly reacting substance of anaphylaxis MRS-A (SRS-A).

In recent years, it has been established that there are at least two cyclooxygenase isoenzymes that are inhibited by the NSAIDs. The first isoenzyme - COF-1 - controls the production of GHG, regulating the integrity of the mucous membrane of the gastrointestinal tract, the function of platelets and the renal blood flow, and the second isoenzyme - COG-2 - participates in the synthesis of PG during inflammation. Moreover, COG-2 is absent under normal conditions, and is formed under the action of some tissue factors that initiate an inflammatory response (cytokines and others). In this regard, it is assumed that the anti-inflammatory effect of the NSAID is due to the inhibition of COG-2, and their unwanted reactions - inhibition of COF-1. The ratio of NSAID activity in terms of blocking COF-1 / COX-2 allows you to judge their potential toxicity. The smaller this value, the more selective the drug in relation to COX-2 and, thereby, less toxic. For example, for meloxicam, it fits 0.33, diclofenac - 2.2, tenoxicam - 15, pyroxicam - 33, indomethacin - 107.

The newest evidence suggests that the NSAIDs not only depress cyclooxygenase metabolism, but also actively affect the synthesis of GHG associated with the mobilization of SA in smooth muscles. Thus, the butadion, inhibits the conversion of cyclic endoprixes into the prostaglandins E2 and F2, and the fenamates besides can block the reception of these substances in the tissues.

An important role in the anti-inflammatory action of the NSAIDs plays their influence on the metabolism and bioe effects of kinines. In therapeutic doses of Indomethacin, Ortofen, Naproxen, Ibuprofen, acetylsalicylic acid (ASC) 70-80% reduce the formation of bradykinin. The basis of this effect is the ability of NSAIDs to propose non-specific inhibition of the interaction of kallicrein with high molecular weight kininogen. The NSAIDs causes a chemical modification of the components of the KININOGENESE reaction, as a result of which due to steric obstacles, the complementary interaction of protein molecules is disturbed and there is no efficient hydrolysis of high molecular weight KININOGEN CALLIREIN. Reducing the formation of bradykinin leads to the braking of the activation of -phospho-rilase, which leads to a decrease in the synthesis of arachidonic acid and, as a result, the manifestation of the effects of the products of its metabolism presented in Fig. one.

No less important is the ability of the NSAID to block the interaction of bradykinin with tissue receptors, which leads to the restoration of the disturbed microcirculation, a decrease in capillaries, reduce the release of the liquid part of the plasma, its proteins, pro-inflammatory factors and uniform elements, which indirectly affect the development of other phases of the inflammatory process. Since the Kallicrein-Kininic system plays the most important role in the development of acute inflammatory reactions, the greatest efficiency of the NSAID is noted in the early stages of inflammation in the presence of a pronounced exudative component.

A certain value in the anti-inflammatory operation mechanism of the NSAIDs has inhibiting the liberation of histamine and serotonin, the blockade of tissue reactions to these biogenic amines, which play a significant role in the inflammatory process. The intramolecular distance between the reaction centers in the antiflogistics molecule (butadion type compounds) is approaching such in the molecule of inflammation mediators (histamine, serotonin). This gives reason to suggest the possibility of competitive interaction of the NSAIDs with receptors or enzyme systems involved in the synthesis processes, release and convert these substances.

As mentioned above, the NSAIDs have a membrane-stabilizing effect. By binding to the G-protein in the cell membrane, the antiflogistics affect the transmission through it membrane signals, the transport of anions is suppressed, affect biological processes dependent on the overall mobility of membrane lipids. They implement its membrane-stabilizing effect by increasing membrane microwave. Penetrated through the cytoplasmic membrane inside the cell, the NSAIDs also affect the functional state of the membrane of cellular structures, in particular, lysosomes and prevent the pro-inflammatory effect of hydrolyzes. Data obtained on the quantitative and qualitative features of the affinity of individual drugs to protein and lipid components of biological membranes, which can explain their membrane effect.

One of the mechanisms of damage to cell membranes is free radical oxidation. Free radicals formed during lipid peroxidation plays an important role in the development of inflammation. Therefore, the oppression of the NSAID peroxidation in the membranes can be considered as a manifestation of their transparent action. It must be borne in mind that one of the main sources of generation of free radicals are the reactions of the metabolism of arachidonic acid. Separate metabolites of its cascade cause accumulation in the focus of inflammation of polymorphous neutrophils and macrophages, the activation of which is also accompanied by the formation of free radicals. NSAIDs, functioning as traps of these compounds, discover the possibility of a new approach to the prevention and therapy of tissue damage caused by free radicals.

In recent years, significant development has been obtained studies of the effect of the NSAID on the cellular mechanisms of the inflammatory response. The NSAIDs reduces the migration of cells into the focus of inflammation and reduce their floogogenic activity, with the influence of polymorphic neutrophils correlates with the inhibition of the lipoxygenase path of the oxidation of arachidonic acid. This alternative path of conversion of arachidonic acid leads to the formation of leukotrienes (LT) (Fig. 1), which correspond to all criteria for inflammation mediators. Benconzaprofen has the ability to influence the 5-log and block the synthesis of LT.

The influence of the NSAP on the cell elements of the late stage of inflammation is less studied - mononuclear cells. Some NSAIDs reduce the migration of monocytes producing free radicals and causing tissue destruction. Although the important role of cell elements in the development of the inflammatory response and therapeutic effect of anti-evaluate means is undoubted, the mechanism of action of the NSAID on migration and the function of these cells is waiting for clarification.

There is an assumption about the release of NSAIDs of natural anti-inflammatory substances from a complex with plasma proteins, which proceeds from the ability of these drugs to outpipe the lysine due to albumin.

b) sensitize receptors to pain mediators (histamine, bradykinin) and mechanical effects, lowering sensitivity threshold;

Fig.1. "Cascade" of arachidonic acid metabolic products and their main effects.

Note: * LT-C 4, D 4, E 4 are the main biological components of a slowly reacting substance of anaphylaxis MRS-A (SRS-A).

Mechanism of action

The main and general element of the mechanism of the NSAID is the oppression of the synthesis of prostaglandins (PG) from arachidonic acid by inhibiting the cyclooxygenase enzyme (PG-synthetase) (Fig. 1).

Fig. one.

PG has versatile biological activity:

1. are mediators of the inflammatory response: cause local extension of vessels, edema, exudation, leukocyte migration and other effects (mainly in 2 and PG-I 2);
2. Sensitize receptors to pain mediators (histamine, bradykinin) and mechanical effects, lowering the threshold of pain sensitivity;
3. Increase the sensitivity of the hypothalamic thermoregulation centers to the action of endogenous pyrogen (interleukin-1 and other), generated in the body under the influence of microbes, viruses, toxins (mainly in PG-E 2).

In recent years, it has been established that there are at least two isoenzyme cyclooxygenases that are inhibited by the NSAIDs. The first isoenzyme - COF-1 (SAL-1 - English) - controls the production of prostaglandins, which regulates the integrity of the mucous membrane of the gastrointestinal tract, the platelet function and renal blood flow, and the second isoenzyme - COF-2 - participates in the synthesis of prostaglandins when inflammation. Moreover, COG-2 in normal conditions is absent, and is formed under the action of some tissue factors, initiating an inflammatory response (cytokines and others). In this regard, it is assumed that the anti-inflammatory effect of the NSAID is due to the inhibition of COG-2, and their unwanted reactions - inhibition of the COF. The ratio of NSAID activity in terms of blocking COF-1 / COX-2 allows you to judge their potential toxicity. The smaller this value, the more selective the drug in relation to COX-2 and, thereby, less toxic. For example, for meloxicama it is 0.33, diclofenac - 2.2, tenoxicam - 15, pyroxicam - 33, indomethacin - 107:

1. Selectivity in relation to COF-1
o Aspirin
o indomethacin
o Ketoprofen.
o Pyroxikams
o Sulindak
2. Moderate selectivity for COF-1
o diclofenak
o ibuprofen
o Naproxen
3. Approximately equal inhibition of COF-1 and COF-2
o Lorunoksikam
4. Moderate selectivity for COF-2
o etodolac
o Meloxicam
o Nimesulid
o Nammaton
5. Pronounced selectivity for COX-2
o Celloxib
o Ropecoxib

Other NSAID Action Mechanisms

The anti-inflammatory effect can be due to the braking of lipid peroxidation, stabilization of membranes with lysosomes (both of these mechanisms prevent damage to cellular structures), decrease in the formation of ATP (the energy supply of the inflammatory response), inhibition of the aggregation of neutrophils (the release of the mediators of inflammation), braking of products of the rheumatoid factor is reduced) In patients with rheumatoid arthritis. Analgesic effect to a certain extent is associated with a violation of pain pulses in the spinal cord (metamizole).

Basic effects

Anti-inflammatory effect

NSAIDs suppress advantage of the exudation phase. The most powerful drugs are indomethacin, diclofenac, phenylbutazone - also act on the proliferation phase (reducing the synthesis of collagen and the tissue sclerosation associated with it), but weaker than on the exudative phase. The NSAID alteration phase is practically not affected. According to anti-inflammatory activity, all NSAIDs are inferior to glucocorticoids, which, inhibiting phospholipase a 2 enzyme, inhibit phospholipid metabolism and violate the formation of both prostaglandins and leukotrienes, which are also essential inflammatory mediators.

Analgesic effect

To a greater extent, it is manifested in pains of weak and medium intensity, which are localized in muscles, joints, tendons, nerve trunks, as well as with head or toothache. With severe visceral pains, most NSPIDs are less effective and inferior at the strength of analgesic effects of a group of morphine (narcotic analgesics). At the same time, a number of controlled studies show a sufficiently high analgesic activity of diclofenac, ketorolac, ketoprofen, metamizole with colic and postoperative pains. The effectiveness of the NSAID in the renal colic arising from patients with urolithiasis is largely due to the braking of PG-E 2 products in the kidneys, a decrease in the renal blood flow and urine formation. This leads to a decrease in pressure in renal pelvis and ureters above the obstruction site and provides a long antening effect. The advantage of NSAIDs in front of narcotic analgesics is that they do not oppress the respiratory center, do not cause euphoria and drug dependence, and with colic matters also the fact that they do not have a spasmodic effect.

Antipyretic effect

NSAIDs are valid only for fever. It does not affect the normal body temperature than they differ from "hypothermic" means (chlorpromazine and others).

Anti-aggregation effect

As a result of the inhibition of COF-1 in platelets, the synthesis of endogenous proagringent thromboxane is suppressed. The strongest and long-term anti-aggregation activity has aspirin, which irreversibly suppresses a platelet ability to aggregation for the entire duration of his life (7 days). The anti-aggregation effect of other NSAIDs is weaker and is reversible. Selective COG-2 inhibitors do not affect platelet aggregation.

Immunosuppressive effect

It is expressed moderately, manifested in prolonged use and has a "secondary" character: reducing the permeability of capillaries, NSAIDs make it difficult to contact immunocompetent cells with antigen and contact antibodies with substrate.

Pharmacokinetics

All NSAIDs are well absorbed in the gastrointestinal tract. Almost fully binds to albumin plasma, displacing some other drugs, and in newborns - bilirubin, which can lead to the development of bilirubin encephalopathy. The most dangerous in this regard by salicylates and phenylbutasone. Most NSPIDs penetrate the synovial liquid of the joints. NSAIDs in the liver are metabolized, stand out through the kidneys.

Medicinal interactions

Quite often patients who receive NSAIDs, and other drugs are prescribed. At the same time, it is necessary to take into account the possibility of their interaction with each other. Thus, the NSAIDs can enhance the effect of indirect anticoagulants and oral hypoglycemic agents. At the same time, they weaken the effect of antihypertensive drugs, increase the toxicity of antibiotic-aminoglycosides, digoxin and some other medicines, which has a significant clinical value and entails a number of practical recommendations.

It should be possible, avoiding the simultaneous appointment of NSAIDs and diuretics, in view of, on the one hand, the weakening of the diuretic effect and, on the other, the risk of renal failure. The most dangerous is the combination of indomethacin with triamtenen.

Many drugs appointed simultaneously with NSAIDs, in turn, can influence their pharmacokinetics and pharmacodynamics:

Sodium Bicarbonate enhances the absorption of the NSAID in the gastrointestinal tract;

The anti-inflammatory action of the NSAIDs enhances glucocorticoids and "slowly acting" (basic) anti-inflammatory agents (drugs of gold, aminohinolines);

The analgesic effect of the NSAIDs is enhanced by narcotic analgesics and sedatives.

The inflammatory process is almost in all cases accompanies rheumatic pathology, significantly reducing the quality of the patient's life. That is why one of the leading directions of therapy of joint diseases is anti-inflammatory treatment. This effect has several groups of drugs: non-steroidal anti-inflammatory agents (NSAIDs), glucocorticoids for systemic and local applications, partly, only as part of comprehensive treatment, - chondroprotectors.

In this article, we will consider a group of drugs specified first - NSAIDs.

Non-steroidal anti-inflammatory funds (NSAIDs)

This is a group of drugs whose effects are anti-inflammatory, antipyretic and anesthetic. The degree of severity of each of them in different medicines is different. These drugs are called non-steroids because they differ in structure from hormonal drugs, glucocorticoids. The latter also have a powerful anti-inflammatory effect, but at the same time they are inherent in the negative properties of steroid hormones.

The mechanism of action of the NSAIDs

The mechanism of action of the NSAID lies in an indiscriminate or electoral oppression (inhibition) by them varieties of the enzyme COG - cyclooxygenase. COW is contained in many tissues of our body and is responsible for the production of various biologically active substances: prostaglandins, prostacyclinins, thrombooxane and others. Prostaglandins, in turn, are mediators of inflammation, and more than them, the more pronounced inflammatory process. NSAIDs, inhibiting COW, reduce the level of content in the tissues of prostaglandins, and the inflammatory process regresses.

Destination scheme NSAIDs

Some NSAIDs have several serious side effects nearby, and other drugs of this group are not characterized. This is due to the features of the mechanism of action: the effects of medicinal substances on various types of cyclooxygenase - COF-1, COF-2 and COF-3.

COF-1 in a healthy person is found in almost all organs and tissues, in particular, in the digestive tract and kidneys, where it performs its most important functions. For example, the synthesized COC of prostaglandins actively participate in maintaining the integrity of the gastric and intestine mucosa, maintaining adequate blood flow in it, reducing the secretion of hydrochloric acid, increasing the pH, the secretion of phospholipids and mucus, stimulating the proliferation (reproduction) of cells. Preparations inhibiting COF-1 cause a decline in the level of prostaglandins not only in the focus of inflammation, but in the whole body, which may entail the negative consequences that will be mentioned below.

COF-2, as a rule, is absent in healthy tissues or is detected, but in minor quantities. It increases its level directly at inflammation and in its very focus. Preparations, selectively depressing COF-2, although they are often accepted systemically, but they act on the hearth, reducing the inflammatory process in it.

COF-3 also participates in the development of pain and fever, but it has no relation to inflammation processes. Separate NSAIDs affect this kind of enzyme and weakly influence the COF-1 and 2. Some authors, however, believe that COF-3, as an independent enzyme isoform, does not exist, and it is an option for COF-1: these questions need Conduct additional research.

Classification of NSAIDs

There is a chemical classification of non-steroidal anti-inflammatory agents based on the characteristics of the structure of the active substance molecule. However, a wide range of readers of biochemical and pharmacological terms Surely little interesting, so we offer you another classification that is based on the selectivity of the inhibition of the COW. According to her, all NSAIDs are divided into:
1. Non-selective (influence on all types of COF, but mainly on COF-1):

Indomethacin;
Ketoprofen;
Pyroxics;
Aspirin;
Diclofenac;
Acycloofenak;
Naproxen;
Ibuprofen.

2. Non-selective, affecting equal to COF-1 and COF-2:

Langnoksikov.

3. Selective (inhibit COF-2):

Meloxicam;
Nimesulide;
Etodolac;
Ropecoxib;
Codexib.

Some of the above-mentioned drugs with anti-inflammatory effect practically do not possess, but have a more painkillers (ketorolac) or antipyretic effect (aspirin, ibuprofen), so we will not speak this article on these drugs. Let's talk about those NSAIDs, the anti-inflammatory effect of which is pronounced the most bright.

Briefly about pharmacokinetics

Non-steroidal anti-inflammatory agents are used inside or intramuscularly.
When ingestion is well absorbed in the digestive tract, their bioavailability is about 70-100%. It is better absorbed in an acidic medium, and the pH shift of the stomach in the alkaline side slows the suction. The maximum concentration of the active substance in the blood is determined 1-2 hours after taking the drug.

With intramuscular administration, the drug is associated with blood proteins by 90-99%, forming functionally active complexes.

It is well penetrated into organs and fabrics, especially in the focus of inflammation and synovial fluid (located in the custody of the joint). NSAIDs are allocated from the body with urine. The half-life varies widely depending on the drug.

Contraindications for the use of NSAIDs

Preparations of this group are undesirable to apply under the following states:

individual hypersensitivity to components;
, as well as other ulcerative damage to the digestive tract;
leoko and thrombopenia;
heavy and;
pregnancy.

Basic Side Effects NSAID

These are:

ulcerogenic action (the ability of drugs of this group to provoke the development of the gastrointestinal tract);
dyspeptic disassembly (discomfort in the area of \u200b\u200bthe stomach, and others);
bronchospasm;
toxic effects on the kidneys (violation of their function, increase blood pressure, nephropathy);
toxic effect on the liver (increase in the activity of hepatic transaminase blood);
toxic effects on blood (reducing the number of uniform elements up to aplastic anemia, manifested);
pregnancy prolongation;
(Skin rash, anaphylaxis).

The number of reports on adverse reactions of drugs of the NSAID group obtained in 2011-2013

Features of therapy NSAIDs

Since the drugs of this group are more or less damaging effect on the gastric mucosa, most of them must be taken necessarily after eating, drinking with sufficient water, and, desirable, with parallel use of drugs to maintain the gastrointestinal tract. As a rule, in this role proton pump inhibitors are inhibitors: omeprazole, Rabeprazole and others.

NSAID treatment should be carried out for minimally permissible time and minimally effective doses.

Persons with impaired kidney function, as well as older patients, as a rule, prescribe a dose below the average therapeutic, since the processes in these categories of patients slowed down: the active ingredient and has an action, and is excreted at a longer period.
Consider individual drugs of the NSAID Group.

Indomethacin (Indomethacin, Metindol)

Release form - pills, capsules.

It has pronounced anti-inflammatory, painkillers and antipyretic effects. Throws aggregation (bonding with each other) platelets. The maximum concentration in the blood is determined 2 hours after the reception, the half-life is 4-11 hours.

Assign, as a rule, inside 25-50 mg 2-3 times a day.

The side effects listed above, this drug is pronounced quite pronounced, so it is currently applied relatively rarely by lifting the championship to others, more secure in this regard to drugs.

Diclofenac (Almiral, Voltaren, Diclac, Dicloberl, Olfen, Olfen and others)

Release form - tablets, capsules, injection, suppositories, gel.

It has a pronounced anti-inflammatory, anesthetic and antipyretic effect. Quickly and completely absorbed in the gastrointestinal tract. The maximum concentration of the active substance in the blood is achieved after 20-60 minutes. Almost 100% is absorbed with blood proteins and is transported by the body. The maximum concentration of the drug in the synovial fluid is determined after 3-4 hours, the half-life of it is equal to 3-6 hours, from plasma of blood - 1-2 hours. Displays with urine, bile and feces.

As a rule, the dose-based dyaclofenac dose is 50-75 mg 2-3 times a day. The maximum daily dose is 300 mg. The form of retard, equal to 100 g of the drug in one tablet (capsule), is accepted once a day. With intramuscular administration, one-time dose is 75 mg, the multiplicity of administration is 1-2 times a day. The drug in the form of gel is applied by a thin layer on the skin in the area of \u200b\u200binflammation, the variety of application is 2-3 times a day.

Etodolac (etol fort)

Release form - 400 mg capsules.

Anti-inflammatory, antipyretic and painkillers of this drug are also pronounced quite pronounced. It has moderate selectivity - acts mainly on COF-2 in the focus of inflammation.

Quickly absorbed from the gastrointestinal tract when taking inside. Bioavailability does not depend on meals and antacid drugs. The maximum concentration of the active substance in the blood is determined after 60 minutes. 95% binds to blood proteins. The half-life of blood plasma is 7 o'clock. It is highlighted from the body mainly with urine.

It is used for emergency or long therapy for rheumatological pathology:, as well as in the case of painful syndrome of any etiology.
It is recommended to take the drug at 400 mg 1-3 times a day after meals. If there is no longer therapy, the dose of the drug should be adjusted 1 time in 2-3 weeks.

Contraindications are standard. The side effects are similar to those of other NSAIDs, but due to the relative selectivity of the drug, they appear less often and expressed to a lesser extent.
Reduces the effect of certain hypotensive drugs, in particular, ACE inhibitors.

Aceclofenac (Aeral, Diclotol, Zerool)

Available in the form of 100 mg tablets.

A decent equivalent of diclofenac with an anti-inflammatory and painkillery effect.
After receiving inside quickly and almost 100% absorbed mucous membranes. With simultaneous meals, the suction rate slows down, but its degree remains the same. Binds with plasma proteins almost completely, in this form, spreading through the body. The concentration of the drug in the synovial fluid is quite high: it reaches 60% of the concentration of it in the blood. The average half-life is 4-4.5 o'clock. Available mainly by the kidneys.

From side effects It should be noted dyspepsia, an increase in the activity of hepatic transaminases, dizziness: these symptoms are found quite often, in 1-10 cases out of 100. Other unwanted reactions are noted much less often, in particular, less than in a single patient for 10,000.

It is possible to reduce the likelihood of the development of side effects by assigning a patient a minimum effective dose as soon as possible.

During the pregnancy and breastfeeding, acecloofenak is not recommended.
Reduces the antihypertensive effect of antihypertensive drugs.

Pyroxikov (Pyroxikov, Fedin-20)

Edition form - 10 mg tablets.

In addition to anti-inflammatory, analgesic and antipyretic effects, there is also an antiagregative effect.

Well absorbed in the gastrointestinal tract. Simultaneous meal slows down the absorption rate, but does not have the degree of exposure. The maximum concentration in the blood is marked after 3-5 hours. The blood concentration is significantly higher with intramuscular administration of the drug, rather than after receiving it orally. By 40-50% penetrates the synovial fluid, found in breast milk. Conducts a number of changes in the liver. Displays with urine and cartoons. The half-life is 24-50 hours.

The anesthetic effect is manifested after half an hour after receiving the tablet and persists during the day.

Dosage preparations vary depending on the disease and range from 10 to 40 mg per day in one or more receptions.

Contraindications and side effects are standard.

Thosexicamins (Texamemen L)

The release form is powder for the preparation of the injection solution.

Application is used in 2 ml (20 mg of the drug) per day. With acute - 40 mg 1 time per day, 5 days in a row at the same time.

Enhances the effects of indirect anticoagulants.

Lorunoksikov (Ksefokam, Larfix, Larats)

The release form is a tablet of 4 and 8 mg, powder for the preparation of a solution for injections containing 8 mg of the drug.

Recommended dose for reception inside 8-16 mg per day 2-3 times. Take a tablet before eating, drinking with plenty of water.

Intramuscularly or intravenously injected 8 mg per 1 time. Multiplicity of administration per day: 1-2 times. The injection solution is required to be prepared immediately before use. Maximum daily dose - 16 mg.
Elderly patients do not need to reduce the dosage of Langnoksikam, however, due to the probability of developing adverse reactions from the gastrointestinal tract, persons with any gastroenterological pathology should be taken with caution.

Meloxico (Movie, Melbek, Remoze, Rekoks, Meloxes and others)

The release form is a tablet of 7.5 and 15 mg, a solution for 2 ml injection in an ampoule, containing 15 mg of the active substance, rectal suppositories, also containing 7.5 and 15 mg of meloxicam.

Selective COF-2 inhibitor. Less frequently than other drugs of the NSAID group causes side effects in the form of kidney and gastropathy defeat.

As a rule, in the first few days of treatment, the drug is applied parenterally. They introduce deep into the muscle of 1-2 ml of solution. When a sharp inflammatory process pokes a bit, the patient is transferred to the tabletled form of meloxicam. Inside it is applied regardless of the meal of 7.5 mg 1-2 times a day.

Celecoxib (Kebrex, Remoxib, Zide, Flogoxy)

The form of release - capsules of 100 and 200 mg of the drug.

The specific COF-2 inhibitor, which has a pronounced anti-inflammatory and painkillers. When applied in therapeutic doses of negative impact on the gastrointestinal mucosa, it practically does not have it, since the COF-1 has a very low degree of affinity, therefore, violations of the synthesis of constitutional prostaglandins does not cause.

As a rule, the celecoxib is taken in a dosage of 100-200 mg per day in 1-2 reception. Maximum daily dose - 400 mg.

Side effects rarely occur. In the case of long-term intake of the drug in high dosage, it is possible to ulcerate the mucous membrane of the digestive tract, gastrointestinal bleeding, agranulocytosis and.

Ropecoxib (Denhebol)

The release form is a solution for injection in 1 ml ampoules, containing 25 mg of active ingredient, pills.

High-selective COX-2 inhibitor with severe anti-inflammatory, painkillers and antipyretic properties. Practically does not affect the mucous membrane of the gastrointestinal tract and on the kidney tissue.

Caution is prescribed by women in the 1st and 2nd trimesters of pregnancy, during breastfeeding, persons suffering or pronounced.

The risk of developing side effects from the gastrointestinal tract increases when taking high dosages of the drug for a long time, as well as in elderly patients.

Ryricoxib (Arcocusia, EXINEF)

Release form - tablets of 60 mg, 90 mg and 120 mg.

Selective COF-2 inhibitor. The stomach prostaglandins synthesis does not affect the platelet function of the impact.

The drug is taken inside, regardless of meals. The recommended dose directly depends on the severity of the disease and varies within 30-120 mg per day in 1 reception. Elderly patients do not need to adjust the dosage.

Side effects develop extremely rarely. As a rule, they are noted by patients taking itaroxib for 1 year or more (with serious rheumatic diseases). The spectrum of unwanted reactions arising in this case is extremely wide.

Nimesulid (Nimegez, Nimesil, Nimid, Aponyl, Nimes, Craftsulid and others)

The release form is 100 mg tablets, granules for the preparation of a suspension for oral administration in sachets containing 1 dose of the drug - 100 mg, gel in a tube.

High-selective COG-2 inhibitor with severe anti-inflammatory, analgesic and antipyretic effect.

Take the drug inside 100 mg twice a day, after meals. The duration of treatment is determined individually. The gel is applied to the area of \u200b\u200bthe lesion, slightly rubbing into the skin. The multiplicity of application is 3-4 times a day.

When prescribing nimesulda, patients of elderly, the dose correction is not required. A dose should be reduced in the event of a severe violation in a patient of the liver and kidney function. A hepatotoxic action can have a hepattotoxic effect.

During pregnancy, especially in the 3rd trimester, it is categorically not recommended to take nimesulide. During breastfeeding period, the drug is also contraindicated.

Nammaton (Simtonon)

Release form - tablets of 500 and 750 mg.

Non-selective inhibitor COG.

One-time dose for an adult patient is 500-750-1000 mg during or after meals. In particularly severe cases, the dose can be increased to 2 grams per day.

Side effects and contraindications are similar to those of other non-selective NSAIDs.
During pregnancy and breastfeeding, it is not recommended.

Combined non-steroidal anti-inflammatory drugs

There are preparations containing two or more actors from the NSAID group, or the NSAID in combination with vitamins or other drugs. Below are their main them.

Dollarken. Contains 50 mg of sodium diclofenac and 500 mg of paracetamol. In this preparation, the pronounced anti-inflammatory effect of diclofenac is combined with the bright analgesic effect of paracetamol. Take the drug inside 1 tablet 2-3 times a day after meals. The maximum daily dose is 3 tablets.
Neurodiklit. Capsules containing 50 mg diclofenac, vitamin B1 and B6, as well as 0.25 mg of vitamin B12. Here, the anesthetic and anti-inflammatory effect of diclofenac is enhanced by the vitamins of the group in, improving the metabolism in the nervous tissue. The recommended dose of the drug is 1-3 capsules per day in 1-3 reception. Take the drug after eating, drinking sufficient liquid.
Olfen-75, produced in the form of a solution for injections, in addition to diclofenac in an amount of 75 mg, also contains 20 mg of lidocaine: due to the presence in the latter solution, the injection of the drug becomes less painful for the patient.
Fanigan. Its composition is similar to the composition of the formation: 50 mg of sodium diclofenac and 500 mg of paracetamol. It is recommended to take 1 tablet 2-3 times a day.
Flamidez. Very interesting, different from other drug. In addition to 50 mg of diclofenac and 500 mg of paracetamol, it also contains 15 mg of serratyptidase, which is a proteolytic enzyme and a fibrinolytic, anti-inflammatory and anti-ethnic effect. Produced in the form of tablets and gel for local applications. The tablet is taken inside, after meals, drinking a glass of water. As a rule, they are prescribed 1 tablet 1-2 times a day. The maximum daily dose is equal to 3rd tablets. The gel is used externally, applying it to the affected skin of the skin 3-4 times a day.
MaxiSiSik. The drug similar to the composition and the action of the flalamsess described above. The difference is the company-producer.
Diplo-P-Farmex. The composition of these tablets is similar to the composition of Dollana. Dosages are the same.
Dollar Same.
Dowx. Same.
Oxalgin-dp. Same.
Cinepar. Same.
Dylicokain. Like Alfen-75, contains sodium diclofenac and lidocaine, but both active substances are in half dosage. Accordingly, it is weaker in action.
Dollarken gel. It contains in its composition of sodium diclofenac, menthol, linseed oil and methylsalicylate. All of these components in one degree or another have an anti-inflammatory effect and potentiate each other effects. The gel is applied to the affected areas of the skin 3-4 times during the day.
Nimid Forte. Tablets containing 100 mg nimesulide and 2 mg of teizanidine. In this drug, the anti-inflammatory and anesthetic effects of nimesulide with the Miorolaxantic (relaxing muscles) of the effect of tizanidine are successfully combined. It is used for acute pain caused by spasm of skeletal muscles (in popular - when the roots is infrained). Take the drug inside after meals, drinking with plenty of liquid. The recommended dose is 2 tablets per day in 2 reception. The maximum duration of treatment is 2 weeks.
Nizalid. As well as Nimid Forte, contains nimesulide and tizanidine in similar dosages. Recommended doses are the same.
Alit. Soluble tablets containing 100 mg nimesulide and 20 mg of dicycloverine, which is a muscle relaxant. Take inside after meals, drinking a glass of liquid. It is recommended to take 1 tablet 2 times a day no longer than 5 days.
Nanogan. The composition of this drug and recommended dosages are similar to those of the Alite described above.
Oxigan Same.