Indications for prescribing NSAIDs. Indications for use and dosage regimen

Inflammation is a process that accompanies, to one degree or another, almost all pathologies of organs and systems. A group of non-steroidal anti-inflammatory drugs successfully fights inflammation, relieves pain and relieves suffering.

The popularity of NSAIDs is understandable:

• the drugs quickly relieve pain and have antipyretic and anti-inflammatory effects;
• modern products are available in various dosage forms: they are convenient to use in the form of ointments, gels, sprays, injections, capsules or suppositories;
• Many of the drugs in this group can be purchased without a prescription.

Despite their availability and universal popularity, NSAIDs are not at all safe group drugs. Uncontrolled use and self-prescription by patients can cause harm to the body. more harm than good. A doctor must prescribe the medicine!

Classification of NSAIDs

The group of non-steroidal anti-inflammatory drugs is very extensive and includes many drugs, varied in chemical structure and mechanisms of action.

The study of this group began in the first half of the last century. Its very first representative is acetylsalicylic acid, the active substance of which is salicylin, was isolated in 1827 from willow bark. After 30 years, scientists learned to synthesize this drug and its sodium salt- the same aspirin that occupies its niche on pharmacy shelves.

Currently in clinical medicine More than 1000 types of drugs based on NSAIDs are used.

The following areas can be distinguished in the classification of these drugs:

By chemical structure

NSAIDs can be derivatives:

• carboxylic acids (salicylic - Aspirin; acetic - Indomethacin, Diclofenac, Ketorolac; propionic - Ibuprofen, Naproxen; nicotinic - niflumic acid);
• pyrosalones (Phenylbutazone);
• oxicams (Piroxicam, Meloxicam);
• coxibs (Celocoxib, Rofecoxib);
• sulfonanilides (Nimesulide);
• alkanones (Nabumetone).

According to the severity of the fight against inflammation

The most important clinical effect for this group of drugs is anti-inflammatory, so it is important classification of NSAIDs is the one that takes into account the strength of this effect. All medicines belonging to this group are divided into those with:

• pronounced anti-inflammatory effect (Aspirin, Indomethacin, Diclofenac, Aceclofenac, Nimesulide, Meloxicam);
• weak anti-inflammatory effect or non-narcotic analgesics(Metamizole (Analgin), Paracetamol, Ketorolac).

By COX inhibition

COX or cyclooxygenase is an enzyme responsible for a cascade of transformations that promotes the production of inflammatory mediators (prostaglandins, histamine, leukotrienes). These substances support and enhance the inflammatory process and increase tissue permeability. There are two types of the enzyme: COX-1 and COX-2. COX-1 is a “good” enzyme that promotes the production of prostaglandins that protect the gastrointestinal mucosa. COX-2 is an enzyme that promotes the synthesis of inflammatory mediators. Depending on what type of COX the drug blocks, there are:

• non-selective COX inhibitors (Butadione, Analgin, Indomethacin, Diclofenac, Ibuprofen, Naproxen, Ketorolac).

They block both COX-2, which reduces inflammation, and COX-1 - long-term use results in unwanted side effects from the gastrointestinal tract;

• selective COX-2 inhibitors (Meloxicam, Nimesulide, Celecoxib, Etodolac).

They selectively block only the COX-2 enzyme, while reducing the synthesis of prostaglandins, but do not have a gastrotoxic effect.

By latest research secrete another third type of enzyme - COX-3, which is found in the cerebral cortex and cerebrospinal fluid. The drug acetaminophen (aceclofenac) selectively affects this enzyme isomer.

Mechanism of action and effects

The main mechanism of action of this group of drugs is the inhibition of the enzyme cyclooxygenase.

Anti-inflammatory effect

Inflammation is maintained and develops with the formation of specific substances: prostaglandins, bradykinin, leukotrienes. At inflammatory process from arachidonic acid with the participation of COX-2, prostaglandins are formed.

NSAIDs block the production of this enzyme, therefore mediators - prostaglandins are not formed, and an anti-inflammatory effect from taking the drug develops.

In addition to COX-2, NSAIDs can also block COX-1, which is also involved in the synthesis of prostaglandins, but is necessary to restore the integrity of the gastrointestinal mucosa. If a drug blocks both types of enzyme, it can have a negative effect on the gastrointestinal tract.

By reducing the synthesis of prostaglandins, swelling and infiltration at the site of inflammation are reduced.

NSAIDs, entering the body, contribute to the fact that another inflammatory mediator, bradykinin, becomes unable to interact with cells, and this contributes to the normalization of microcirculation, narrowing of capillaries, which has a positive effect to relieve inflammation.

Under the influence of this group of drugs, the production of histamine and serotonin decreases - biologically active substances aggravating inflammatory changes in the body and contributing to their progression.

NSAIDs inhibit peroxidation in cell membranes, and free radicals are known to be a powerful factor that supports inflammation. Inhibition of peroxidation is one of the directions in the anti-inflammatory effect of NSAIDs.

Analgesic effect

The analgesic effect when taking NSAIDs is achieved due to the ability of drugs in this group to penetrate the central nervous system and suppress the activity of pain sensitivity centers there.

During the inflammatory process, a large accumulation of prostaglandins causes hyperalgesia - increased sensitivity to pain. Since NSAIDs help reduce the production of these mediators, pain threshold the patient automatically increases: when prostaglandin synthesis stops, the patient feels pain less acutely.

Among all NSAIDs, there is a separate group of drugs that have an unexpressed anti-inflammatory effect, but a strong pain reliever - these are non-narcotic analgesics: Ketorolac, Metamizole (Analgin), Paracetamol. They can eliminate:

• head, dental, joint, muscle, menstrual pain, pain due to neuritis;
• pain mainly inflammatory in nature.

Unlike narcotic painkillers, NSAIDs do not act on opioid receptors, which means:

• do not cause drug dependence;
• do not depress the respiratory and cough centers;
• do not lead to constipation with frequent use.

Antipyretic effect

NSAIDs have an inhibitory, inhibitory effect on the production of substances in the central nervous system that excite the thermoregulation center in the hypothalamus - prostaglandins E1, interleukins-11. The drugs inhibit the transmission of excitation in the nuclei of the hypothalamus, and heat generation decreases - elevated temperature the body is normalized.

The effect of drugs occurs only when high temperature body, NSAIDs do not have this effect when normal level temperature.

Antithrombotic effect

This effect is most pronounced in acetylsalicylic acid (aspirin). The drug is able to inhibit platelet aggregation (sticking together). It is widely used in cardiology as an antiplatelet agent - a drug that prevents the formation of blood clots and is prescribed for their prevention in heart diseases.

Indications for use

It is unlikely that any other group of drugs can “boast” of such a wide list of indications for use that NSAIDs have. It is diversity clinical cases and diseases for which drugs have the desired effect, makes NSAIDs one of the most commonly recommended drugs by doctors.

Indications for the use of NSAIDs are:

• rheumatological diseases, gouty and psoriatic arthritis;
• neuralgia, radiculitis with radicular syndrome (lower back pain radiating to the leg);
• other diseases of the musculoskeletal system: osteoarthritis, tendovaginitis, myositis, traumatic injuries;
• renal and hepatic colic(as a rule, a combination with antispasmodics is indicated);
• fever above 38.5⁰С;
• inflammatory pain syndrome;
• antiplatelet therapy (aspirin);
• pain in postoperative period.

Since inflammatory pain accompanies up to 70% of all diseases, it becomes obvious how wide the range of prescriptions for this group of drugs is.

NSAIDs are the drugs of choice for relief and relief acute pain for articular pathologies of various origins, neurological radicular syndromes– lumbodynia, sciatica. It should be understood that NSAIDs do not affect the cause of the disease, but only relieve acute pain. For osteoarthritis, drugs have only a symptomatic effect and do not prevent the development of joint deformation.

For cancer patients, doctors may recommend NSAIDs in combination with opioid analgesics to reduce the dosage of the latter, as well as to provide a more pronounced and lasting analgesic effect.

NSAIDs are prescribed for painful menstruation, conditioned increased tone uterus due to overproduction of prostaglandin-F2a. The drugs are prescribed at the first appearance of pain at the beginning or on the eve of menstruation for a course of up to 3 days.

This group of drugs is not at all harmless and has side effects and unwanted reactions, so a doctor should prescribe NSAIDs. Uncontrolled use and self-medication can lead to the development of complications and unwanted side effects.

Many patients wonder: which NSAID is the most effective and best relieves pain? A definite answer to this question cannot be given, since NSAIDs should be selected for the treatment of an inflammatory disease for each patient individually. The choice of drug should be made by a doctor, and is determined by its effectiveness and tolerability side effects. There is no best NSAID for all patients, but there is a best NSAID for each individual patient!

Side effects and contraindications

On the part of many organs and systems, NSAIDs can cause unwanted effects and reactions, especially with frequent and uncontrolled use.

Gastrointestinal disorders

The most common side effect for non-selective NSAIDs. 40% of all patients receiving NSAIDs experience digestive disorders, 10-15% have erosions and ulcerative changes in the gastrointestinal mucosa, and 2-5% have bleeding and perforation.

The most gastrotoxic are Aspirin, Indomethacin, Naproxen.

Nephrotoxicity

The second most common group of adverse reactions that occurs while taking medications. Initially, functional changes in the functioning of the kidneys may develop. Then, with long-term use (from 4 months to six months) it develops organic pathology with the formation of renal failure.

Decreased blood clotting

This effect is more likely to occur in patients already taking indirect anticoagulants(Heparin, Warfarin), or having liver problems. Low coagulability can lead to spontaneous bleeding.

Liver disorders

Liver damage can occur from any NSAID, especially when drinking alcohol, even in small doses. With long-term (more than a month) use of Diclofenac, Phenylbutazone, Sulindac, toxic hepatitis with jaundice may develop.

Disorders of the cardiovascular and hematopoietic system

Changes in the blood count with the occurrence of anemia and thrombocytopenia develop most often when taking Analgin, Indomethacin, and Acetylsalicylic acid. If the hematopoiesis sprouts are not damaged bone marrow, 2 weeks after drug withdrawal, picture in peripheral blood normalizes and pathological changes disappear.

In patients with a history of arterial hypertension or risks of coronary heart disease, with long-term use of NSAIDs, the figures blood pressure may “grow up” - destabilization of hypertension develops; also, when taking both non-selective and selective anti-inflammatory drugs, there is a possibility of increasing the risk of developing myocardial infarction.

Allergic reactions

In case of individual intolerance to the drug, as well as in persons with a predisposition to hyperergic reactions (suffering bronchial asthma allergic origin, hay fever) may be observed various manifestations allergies to NSAIDs - from urticaria to anaphylaxis.

Allergic manifestations account for 12 to 14% of all adverse reactions on this group drugs and are more common when taking Phenylbutazone, Analgin, Amidopyrine. But they can be observed on absolutely any representative of the group.

Allergies can manifest as itchy rashes, swelling skin and mucous membranes, allergic rhinitis, conjunctiva, urticaria. Quincke's edema and anaphylactic shock up to 0.05% of all complications. When taking ibuprofen, hair loss and even baldness can sometimes occur.

Undesirable effects during pregnancy

Some NSAIDs have a teratogenic effect on the fetus: taking aspirin in the first trimester can lead to splitting upper sky in the fetus. IN last weeks pregnancy, NSAIDs inhibit the onset of labor. Due to inhibition of prostaglandin synthesis, the motor activity of the uterus decreases.

There is no optimal NSAID without side effects. Gastrotoxic reactions are less pronounced in selective NSAIDs (Meloxicam, Nimesulide, Aceclofenac). But for each patient the drug should be selected individually, taking into account its concomitant diseases and tolerability.

Reminder when taking NSAIDs. What the patient should know

Patients should remember that a “magic” pill that perfectly eliminates toothache, headache or other pain may not be harmless to their body, especially if it is taken uncontrolled and not as prescribed by a doctor.

There are a number of simple rules that patients must follow when taking NSAIDs:

1. If the patient has the opportunity to choose an NSAID, one should choose selective drugs that have fewer side effects: aceclofenac, movalis, nise, celecoxib, rofecoxib. The most aggressive for the stomach are aspirin, ketorolac, and indomethacin.
2. If the patient has a history of peptic ulcer or erosive changes, gastropathy, and the doctor prescribed anti-inflammatory drugs to relieve acute pain, they should be taken for no more than five days (until the inflammation subsides) and only under the protection of inhibitors proton pump(PPI): omeprazole, rameprazole, pantoprozole. Thus, the toxic effect of NSAIDs on the stomach is neutralized and the risk of recurrence of erosive or ulcerative processes is reduced.
3. Some diseases require constant use of anti-inflammatory drugs. If the doctor recommends taking NSAIDs regularly, before long-term use the patient needs to undergo an FGDS and examine the condition gastrointestinal tract. If the examination reveals even minor changes in the mucous membrane, or the patient has subjective complaints about the digestive organs, NSAIDs should be taken together with inhibitors proton pump(omeprazole, pantoprazole) constantly.
4. When prescribing aspirin for the prevention of blood clots, persons over 60 years of age should also undergo gastroscopy once a year, and if there are risks from the gastrointestinal tract, they should constantly take a drug from the PPI group.
5. If the patient's condition worsens as a result of taking NSAIDs, allergic reactions, stomach pain, weakness, pale skin, worsening breathing or other manifestations of individual intolerance, you should immediately consult your doctor.

Individual characteristics of drugs

Let's consider the currently popular representatives of NSAIDs, their analogues, dosage and frequency of administration, indications for use.

Acetylsalicylic acid (Aspirin, Aspirin UPSA, Aspirin Cardio, Thrombo ACC)

Despite the emergence of new NSAIDs, aspirin continues to be actively used in medical practice not only as an antipyretic and anti-inflammatory drug, but also as an antiplatelet agent for diseases of the heart and blood vessels.

The drug is prescribed in the form of tablets orally after meals.

The drug has anti-inflammatory and antipyretic effects when feverish conditions, headaches, migraines, rheumatological diseases, neuralgia.

Drugs such as Citramon, Askofen, Cardiomagnyl contain acetylsalicylic acid.

Acetylsalicylic acid has many side effects, especially negatively affecting the gastric mucosa. To reduce the ulcerogenic effects, aspirin should be taken after meals, and the tablets should be washed down with water.

A history of gastric and duodenal ulcers are contraindications for the use of this drug.

Currently in production modern drugs with alkalizing additives, or in the form of effervescent tablets containing acetylsalicylic acid, which is better tolerated and provides less irritant effect on the gastric mucosa.

Nimesulide (Nise, Nimesil, Nimulid, Kokstral)

The drug has anti-inflammatory, analgesic and antipyretic effects. It has an effect in osteoarthritis, tendovaginitis, pain syndrome due to injuries, and the postoperative period.

Available under different trade names in the form of tablets of 0.1 and 0.2 g, granules for oral administration in sachets of 2 g (active ingredient), 1% suspension for oral administration, 1% gel for external use. The variety of release forms makes the drug very popular for use.

Nimesulide is prescribed orally for adults at 0.1-0.2 g 2 times a day, for children - at a rate of 1.5 mg/kg 2-3 times a day. The gel is applied to the painful area of ​​skin 2-3 times a day for no more than 10 days in a row.

Gastric ulcers, severe liver and kidney dysfunction, pregnancy and breastfeeding are contraindications for taking the medicine.

Meloxicam (Movalis, Artrosan, Melox, Meloflex)

The drug belongs to the selective NSAIDs. Its undoubted advantages, in contrast to non-selective drugs, are less ulcerogenic effects on the gastrointestinal tract and better tolerability.

It has pronounced anti-inflammatory and analgesic activity. Used when rheumatoid arthritis, arthrosis, ankylosing spondylitis, to relieve episodes of pain of inflammatory origin.

Available in the form of tablets of 7.5 and 15 mg, rectal suppositories of 15 mg. Regular daily dose for adults 7.5-15 mg.

It should be borne in mind that the lower incidence of side effects when taking meloxicam does not guarantee their absence, as with other NSAIDs, the drug may develop individual intolerance, increased blood pressure, dizziness, dyspepsia, and hearing loss are rarely observed while taking meloxicam.

You should not get carried away with taking the drug if you have a peptic ulcer or a history of erosive processes in the stomach; its use is contraindicated during pregnancy and lactation.

Diclofenac (Ortofen, Voltaren, Dikloberl, Diclobene, Naklofen)

Diclofenac injections for many patients suffering from “lumbago” in the lower back become “saving injections” that help relieve pain and relieve inflammation.

The drug is available in different dosage forms: as a 2.5% solution in ampoules for intramuscular administration, tablets of 15 and 25 mg, rectal suppositories 0.05 g, 2% ointment for external use.

In an adequate dose, diclofenac rarely causes side effects, but they are possible: disorders of the digestive system (epigastric pain, nausea, diarrhea), headaches, dizziness, allergic reactions. If side effects occur, you should stop taking the medicine and consult your doctor.

Today, diclofencan sodium preparations are produced that have a prolonged effect: dieloberl retard, voltaren retard 100. The effect of one tablet lasts throughout the day.

Aceclofenac (Aertal)

Some researchers call Airtal the leader among NSAIDs, because according to data clinical trials, this drug caused much fewer side effects than other selective NSAIDs.

It cannot be reliably stated that aceclofenac is “the best of the best,” but the fact that side effects when taking it are less pronounced than when taking other NSAIDs is a clinically proven fact.

The drug is available in the form of tablets of 0.1 g. It is used for chronic and acute pain of an inflammatory nature.

Side effects in in rare cases occur and manifest themselves in the form of dyspepsia, dizziness, sleep disorders, allergic skin reactions.

People with problems with the gastrointestinal tract should take aceclofenac with caution. The drug is contraindicated during pregnancy and breastfeeding.

Celecoxib (Celebrex)

A relatively new, modern selective NSAID that has a reduced negative effect on the gastric mucosa.

The drug is available in capsules of 0.1 and 0.2 g. It is used for joint pathologies: rheumatoid arthritis, arthrosis, synovitis, as well as other inflammatory processes in the body accompanied by pain.

Prescribed 0.1 g 2 times a day or 0.2 g once. The frequency and timing of administration must be specified by the attending physician.

Like all NSAIDs, celecoxib is not without undesirable effects and side effects, albeit to a lesser extent. Patients taking the medicine may experience dyspepsia, stomach pain, sleep disturbances, changes in the blood count with the development of anemia. If side effects occur, you should stop using the medicine and consult a doctor.

Ibuprofen (Nurofen, MIG 200, Bonifen, Dolgit, Ibupron)

One of the few NSAIDs that have not only anti-inflammatory, analgesic and antipyretic effects, but also immunomodulatory ones.

There is evidence of the ability of ibuprofen to influence the production of interferon in the body, which provides a better immune response and improves nonspecific defensive reaction body.

The drug is taken for pain syndrome of inflammatory origin, both in acute conditions and in chronic pathology.

The drug can be produced in the form of tablets 0.2; 0.4; 0.6 g, chewable tablets, dragees, extended-release tablets, capsules, syrup, suspension, cream and gel for external use.

Apply ibuprofen internally and externally, rubbing the affected areas and places on the body.

Ibuprofen is usually well tolerated and has relatively weak ulcerogenic activity, which gives it a great advantage over acetylsalicylic acid. Sometimes, while taking ibuprofen, belching, heartburn, nausea, flatulence, increased blood pressure, and allergic skin reactions may occur.

During exacerbation of peptic ulcer disease, pregnancy and breastfeeding, this drug should not be taken.

Pharmacy displays are full of various representatives of NSAIDs, advertising on TV screens promises that the patient will forget about the pain forever by taking exactly “that” anti-inflammatory drug... Doctors strongly recommend: if pain occurs, you should not self-medicate! The choice of NSAIDs should be made only under the supervision of a specialist!

NSAIDs today are a dynamically developing class of drugs. This is due to the wide range of applications of this pharmaceutical group, which has antipyretic and analgesic activity.

NSAIDs are a whole group of drugs

NSAIDs block the action of the enzyme cyclooxygenase (COX), inhibiting the synthesis of prostaglandins from arachidonic acid. Prostaglandins in the body are mediators of inflammation, lower the threshold of sensitivity to pain, inhibit lipid peroxidation and inhibit neutrophil aggregation.
The main effects of NSAIDs include:

• Anti-inflammatory. Suppress the exudative phase of inflammation, and, to a lesser extent, the proliferative phase. Diclofenac and Indomethacin are the most powerful drugs for this effect. But the anti-inflammatory effect is less pronounced than that of glucocorticosteroids.
  Practitioners use a classification according to which all NSAIDs are divided into: drugs with high anti-inflammatory activity and drugs with weak anti-inflammatory activity. High activity Aspirin, Indomethacin, Diclofenac, Piroxicam, Ibuprofen and many others possess. This group includes a large number of various drugs. Paracetamol, Metamizole, Ketorolac and some others have low anti-inflammatory activity. The group is small.
• Painkiller. Most pronounced in Diclofenac, Ketoralac, Metamizol, Ketaprofen. Used for pain of low and medium intensity: dental, muscle, headache. Effective for renal colic, because Not . Compared with narcotic analgesics(morphine group), do not have an inhibitory effect on respiratory center, are not addictive.
• Antipyretic. All drugs in varying degrees have this property. But it only appears in the presence of fever.
• Anti-aggregation. Manifests itself due to suppression of thromboxane synthesis. This effect is most pronounced with Aspirin.
• Immunosuppressive. It manifests itself secondarily due to deterioration of the permeability of capillary walls.

Indications for use of NSAIDs

The main indications include:

• Rheumatic diseases. Includes rheumatism, rheumatoid arthritis, ankylosing spondylitis, gouty and psoriatic arthritis, and Reiter's disease. For these diseases use of NSAIDs is symptomatic and does not affect pathogenesis. That is, taking NSAIDs cannot slow down the development of the destructive process in rheumatoid arthritis or prevent joint deformation. But patient complaints of pain, stiffness in the joints initial stages diseases become less common.
• Diseases of the musculoskeletal system of a non-rheumatic nature. This includes injuries (bruises, sprains), myositis, tendovaginitis. For the above diseases, NSAIDs are used orally, in the form of injections. And external agents (ointments, creams, gels) that contain active ingredients of this group are very effective.
• Neurological diseases. Lumbago, radiculitis, myalgia. Combinations of various forms of drug release are often prescribed simultaneously (ointment and tablets, injections and gel, etc.)
• Renal, . Drugs from the NSAID group are effective for all types of colic, because... do not cause additional spasm of smooth cell muscle structures.
• Pain symptoms of various etiologies. Pain relief in the postoperative period, toothache and headache.
• Dysmenorrhea. NSAIDs are used to relieve pain in primary dysmenorrhea and to reduce the amount of blood loss. Good effect Naproxen and Ibuprofen are provided, which are recommended to be taken on the eve of menstruation and for three days thereafter. Such short-term courses prevent the occurrence of unwanted effects.
• Fever. Antipyretic drugs are recommended to be taken at body temperatures above 38.5 °C.
• Prevention of thrombosis. To prevent the formation of blood clots, low dosage of Acetylsalicylic acid is used. Prescribed to prevent heart attacks, strokes with various forms coronary disease hearts.

Undesirable effects and contraindications

Drugs of the NSAID group provide Negative influence on the:

1. and intestines
2. Liver
3. Kidneys
4. Blood
5. Nervous system

The most common area that suffers from taking NSAIDs is the stomach. This manifests itself as nausea, diarrhea, pain in the epigastric region and other dyspeptic complaints. There is even such a syndrome - NSAID gastropathy, the occurrence of which is directly related to the use of NSAIDs. Elderly patients, with a history of gastric ulcers, and concurrently taking glucocorticosteroid drugs are especially at risk of pathology.

NSAIDs are different drugs, but their effect is the same!

The likelihood of developing NSAID gastropathy increases with long-term use of drugs in high dose, as well as when taking two or more NSAIDs. Lansoprazole, Esomeprazole and other proton pump inhibitors are used to protect the gastric mucosa. may be in the form of severe toxic hepatitis, or may manifest itself as transient dysfunction with an increase in the level of transaminases in the blood.

The liver is most often affected when taking Indomethacin, Phenylbutazone, and Aspirin. On the part of the kidneys, a decrease in diuresis may develop, acute renal failure, nephrotic syndrome, as a result of damage to the kidney tubules. The greatest danger is represented by Ibuprofen and Naproxen.

In the blood, clotting processes are disrupted and anemia occurs. Diclofenac, Piroxicam, Butadione are dangerous in terms of side effects from the blood system. Often undesirable effects from nervous system occur when taking Aspirin, Indomethacin. And they manifest themselves as headache, tinnitus, nausea, and sometimes vomiting, mental disorders. Taking NSAIDs is contraindicated in the case.

The inflammatory process in almost all cases accompanies rheumatic pathology, significantly reducing the patient’s quality of life. That is why one of the leading areas of treatment for joint diseases is anti-inflammatory treatment. Several groups of drugs have this effect: non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids for systemic and local use, partly, only in complex treatment, – chondroprotectors.

In this article we will look at the group of drugs listed first - NSAIDs.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

This is a group of drugs whose effects are anti-inflammatory, antipyretic and analgesic. The severity of each of them varies from drug to drug. These drugs are called nonsteroidal because they differ in structure from hormonal drugs, glucocorticoids. The latter also have a powerful anti-inflammatory effect, but at the same time they have the negative properties of steroid hormones.

Mechanism of action of NSAIDs

The mechanism of action of NSAIDs is their non-selective or selective inhibition (inhibition) of varieties of the COX enzyme - cyclooxygenase. COX is found in many tissues of our body and is responsible for the production of various biologically active substances: prostaglandins, prostacyclins, thromboxane and others. Prostaglandins, in turn, are mediators of inflammation, and the more of them, the more pronounced the inflammatory process. NSAIDs, by inhibiting COX, reduce the level of prostaglandins in tissues, and the inflammatory process regresses.

NSAID prescription regimen

Some NSAIDs have a number of quite serious side effects, while other drugs in this group are not characterized as such. This is due to the peculiarities of the mechanism of action: influence medicinal substances for different types of cyclooxygenase - COX-1, COX-2 and COX-3.

In a healthy person, COX-1 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, prostaglandins synthesized by COX are actively involved in maintaining the integrity of the gastric and intestinal mucosa, maintaining adequate blood flow in it, reducing the secretion of hydrochloric acid, increasing pH, secretion of phospholipids and mucus, stimulating cell proliferation (reproduction). Drugs that inhibit COX-1 cause a decrease in the level of prostaglandins not only in the site of inflammation, but throughout the body, which can lead to Negative consequences, which will be discussed below.

COX-2, as a rule, is absent in healthy tissues or is found, but in insignificant quantities. Its level increases directly during inflammation and at its very source. Drugs that selectively inhibit COX-2, although often taken systemically, act specifically on the lesion, reducing the inflammatory process in it.

COX-3 is also involved in the development of pain and fever, but it has nothing to do with inflammation. Some NSAIDs act specifically on this type of enzyme and have little effect on COX-1 and 2. Some authors, however, believe that COX-3, as an independent isoform of the enzyme, does not exist, and is a variant of COX-1: these questions require conducting additional research.

Classification of NSAIDs

Exists chemical classification non-steroidal anti-inflammatory drugs, based on the structural features of the active substance molecule. However, biochemical and pharmacological terms are probably of little interest to a wide range of readers, so we offer you another classification, which is based on the selectivity of COX inhibition. According to it, all NSAIDs are divided into:
1. Non-selective (affect all types of COX, but mainly COX-1):

• Indomethacin;
• Ketoprofen;
• Piroxicam;
• Aspirin;
• Diclofenac;
• Acyclofenac;
• Naproxen;
• Ibuprofen.

2. Non-selective, affecting equally COX-1 and COX-2:

• Lornoxicam.

3. Selective (inhibit COX-2):

• Meloxicam;
• Nimesulide;
• Etodolac;
• Rofecoxib;
• Celecoxib.

Some of the drugs listed above have virtually no anti-inflammatory effect, but rather have an analgesic (Ketorolac) or antipyretic effect (Aspirin, Ibuprofen), so we will not talk about these drugs in this article. Let's talk about those NSAIDs whose anti-inflammatory effect is most pronounced.

Briefly about pharmacokinetics

Nonsteroidal anti-inflammatory drugs are used orally or intramuscularly.
When taken orally, they are well absorbed in the digestive tract, their bioavailability is about 70-100%. They are better absorbed in an acidic environment, and a shift in gastric pH to the alkaline side slows down absorption. The maximum concentration of the active substance in the blood is determined 1-2 hours after taking the drug.

When administered intramuscularly, the drug binds to blood proteins by 90-99%, forming functionally active complexes.

Penetrate well into organs and tissues, especially into the site of inflammation and synovial fluid(located in the joint cavity). NSAIDs are excreted from the body in the urine. The half-life varies widely depending on the drug.

Contraindications to the use of NSAIDs

It is undesirable to use drugs in this group in the following conditions:

• individual hypersensitivity to components;
• , as well as others ulcerative lesions digestive tract;
• leuko- and thrombopenia;
• heavy and;
• pregnancy.

Main side effects of NSAIDs

These are:

• ulcerogenic effect (the ability of drugs in this group to provoke the development of the gastrointestinal tract);
• dyspeptic disorders (stomach discomfort, etc.);
• bronchospasm;
• toxic effects on the kidneys (impaired kidney function, increased blood pressure, nephropathy);
• toxic effects on the liver (increased activity of liver transaminases in the blood);
• toxic effect on the blood (reduction in the amount shaped elements up to aplastic anemia, manifested);
• prolongation of pregnancy;
• (skin rashes, anaphylaxis).

Number of reports of adverse reactions of NSAID drugs received in 2011-2013

Features of NSAID therapy

Since drugs in this group, to a greater or lesser extent, have a damaging effect on the gastric mucosa, most of them must be taken after meals, with a sufficient amount of water, and, preferably, with the parallel use of drugs to maintain the gastrointestinal tract. As a rule, proton pump inhibitors play this role: Omeprazole, Rabeprazole and others.

Treatment with NSAIDs should be carried out for the minimum permissible time and in the minimum effective doses.

Persons with impaired renal function, as well as elderly patients, are usually prescribed a dose lower than the average therapeutic dose, since the processes in these categories of patients are slowed down: the active substance both has an effect and is eliminated over a longer period.
Let us consider individual drugs of the NSAID group in more detail.

Indomethacin (Indomethacin, Methindol)

Release form: tablets, capsules.

It has a pronounced anti-inflammatory, analgesic and antipyretic effect. Inhibits the aggregation (sticking together) of platelets. The maximum concentration in the blood is determined 2 hours after administration, the half-life is 4-11 hours.

Prescribed, as a rule, 25-50 mg orally 2-3 times a day.

The side effects listed above are quite pronounced for this drug, so at present it is used relatively rarely, giving way to other drugs that are safer in this regard.

Diclofenac (Almiral, Voltaren, Diklak, Dikloberl, Naklofen, Olfen and others)

Release form: tablets, capsules, injection solution, suppositories, gel.

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

As a rule, the recommended dose of diclofenac for adults is 50-75 mg 2-3 times a day orally. The maximum daily dose is 300 mg. The retard form, equal to 100 g of the drug in one tablet (capsule), is taken once a day. When administered intramuscularly single dose is 75 mg, frequency of administration is 1-2 times a day. The drug in gel form is applied thin layer on the skin in the area of ​​inflammation, frequency of application – 2-3 times a day.

Etodolac (Etol Fort)

Release form: 400 mg capsules.

The anti-inflammatory, antipyretic and analgesic properties of this drug are also quite pronounced. It has moderate selectivity - it acts predominantly on COX-2 at the site of inflammation.

Rapidly absorbed from the gastrointestinal tract when taken orally. Bioavailability is independent of food intake and antacid medications. The maximum concentration of the active substance in the blood is determined after 60 minutes. 95% binds to blood proteins. The half-life from blood plasma is 7 hours. It is excreted from the body mainly in urine.

It is used for emergency or long-term treatment of rheumatological pathology: as well as in the case of pain syndrome of any etiology.
It is recommended to take the drug 400 mg 1-3 times a day after meals. If long-term therapy is necessary, the dose medicine should be adjusted once every 2-3 weeks.

Contraindications are standard. Side effects are similar to those of other NSAIDs, however, due to the relative selectivity of the drug, they appear less frequently and are less pronounced.
Reduces the effect of some antihypertensive drugs, in particular, ACE inhibitors.

Aceclofenac (Aertal, Diclotol, Zerodol)

Available in the form of 100 mg tablets.

A worthy analogue of diclofenac with a similar anti-inflammatory and analgesic effect.
After oral administration, it is quickly and almost 100% absorbed by the gastric mucosa. When eating at the same time, the rate of absorption slows down, but its degree remains the same. It binds to plasma proteins almost completely, spreading throughout the body in this form. The concentration of the drug in the synovial fluid is quite high: it reaches 60% of its concentration in the blood. The average half-life is 4-4.5 hours. It is excreted primarily by the kidneys.

Side effects include dyspepsia, increased activity of liver transaminases, dizziness: these symptoms occur quite often, in 1-10 cases out of 100. Others unwanted reactions are observed much less frequently, in particular, in less than one patient per 10,000.

The likelihood of side effects can be reduced by prescribing the patient the minimum effective dose in the shortest possible time.

It is not recommended to take aceclofenac during pregnancy and breastfeeding.
Reduces the antihypertensive effect of antihypertensive drugs.

Piroxicam (Piroxicam, Fedin-20)

Release form: 10 mg tablets.

In addition to anti-inflammatory, analgesic and antipyretic effects, it also has an antiplatelet effect.

Well absorbed from the gastrointestinal tract. Simultaneous use food slows down the rate of absorption, but does not affect the degree of its effect. The maximum concentration in the blood is observed after 3-5 hours. The concentration in the blood is much higher when the drug is administered intramuscularly than after taking it orally. Penetrates 40-50% into synovial fluid and is found in breast milk. Undergoes a number of changes in the liver. Excreted in urine and feces. The half-life is 24-50 hours.

The analgesic effect appears within half an hour after taking the tablet and persists throughout the day.

Dosages of the drug vary depending on the disease and range from 10 to 40 mg per day in one or more doses.

Contraindications and side effects are standard.

Tenoxicam (Texamen-L)

Release form: powder for the preparation of solution for injection.

Apply intramuscularly at 2 ml (20 mg of the drug) per day. In acute cases - 40 mg 1 time per day for 5 days in a row at the same time.

Enhances the effects of indirect anticoagulants.

Lornoxicam (Xefocam, Larfix, Lorakam)

Release form: tablets of 4 and 8 mg, powder for the preparation of solution for injection containing 8 mg of the drug.

The recommended dose for oral administration is 8-16 mg per day 2-3 times. The tablet should be taken before meals with a drink big amount water.

8 mg is administered intramuscularly or intravenously at a time. Frequency of administrations per day: 1-2 times. The injection solution must be prepared immediately before use. The maximum daily dose is 16 mg.
Elderly patients do not need to reduce the dosage of lornoxicam; however, due to the likelihood of adverse reactions from the gastrointestinal tract, persons with any gastroenterological pathology should take it with caution.

Meloxicam (Movalis, Melbek, Revmoxicam, Recoxa, Melox and others)

Release form: tablets of 7.5 and 15 mg, injection solution of 2 ml in an ampoule containing 15 mg of active substance, rectal suppositories also containing 7.5 and 15 mg of Meloxicam.

Selective COX-2 inhibitor. Less common than other drugs in the NSAID group, it causes side effects such as kidney damage and gastropathy.

As a rule, the drug is administered parenterally in the first few days of treatment. 1-2 ml of solution is injected deep into the muscle. When the acute inflammatory process subsides a little, the patient is transferred to the tablet form of meloxicam. It is taken orally, regardless of food intake, 7.5 mg 1-2 times a day.

Celecoxib (Celebrex, Revmoxib, Zycel, Flogoxib)

Release form: capsules of 100 and 200 mg of the drug.

A specific inhibitor of COX-2, which has a pronounced anti-inflammatory and analgesic effect. When used in therapeutic doses It has virtually no negative effect on the mucous membrane of the gastrointestinal tract, since it has a very low degree of affinity for COX-1, therefore, it does not cause disruption in the synthesis of constitutional prostaglandins.

As a rule, celecoxib is taken at a dosage of 100-200 mg per day in 1-2 doses. The maximum daily dose is 400 mg.

Side effects are rare. In case of long-term use of the drug in high dosage, ulceration of the mucous membrane of the digestive tract, gastrointestinal bleeding, agranulocytosis, etc. is possible.

Rofecoxib (Denebol)

Release form: solution for injection in 1 ml ampoules containing 25 mg of active substance, tablets.

A highly selective COX-2 inhibitor with pronounced anti-inflammatory, analgesic and antipyretic properties. It has virtually no effect on the mucous membrane of the gastrointestinal tract and kidney tissue.

Prescribed with caution to women in the 1st and 2nd trimesters of pregnancy, during breastfeeding, to persons suffering or severe.

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

Etoricoxib (Arcoxia, Exinef)

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

Selective COX-2 inhibitor. It does not affect the synthesis of gastric prostaglandins and has no effect on platelet function.

The drug is taken orally regardless of food intake. The recommended dose directly depends on the severity of the disease and varies between 30-120 mg per day in 1 dose. Elderly patients do not need to adjust the dosage.

Side effects are extremely rare. As a rule, they are noted by patients taking etoricoxib for 1 year or more (for serious rheumatic diseases). The range of undesirable reactions that arise in this case is extremely wide.

Nimesulide (Nimegesic, Nimesil, Nimid, Aponil, Nimesin, Remesulide and others)

Release form: 100 mg tablets, granules for preparing a suspension for oral administration in sachets containing 1 dose of the drug - 100 mg each, gel in a tube.

A highly selective COX-2 inhibitor with pronounced anti-inflammatory, analgesic and antipyretic effects.

Take the drug orally, 100 mg twice a day, after meals. The duration of treatment is determined individually. The gel is applied to the affected area, lightly rubbing into the skin. Frequency of application – 3-4 times a day.

When prescribing Nimesulide to elderly patients, no dose adjustment is required. The dose should be reduced if severe violation the patient's liver and kidney function. May have a hepatotoxic effect, inhibiting liver function.

During pregnancy, especially in the 3rd trimester, taking nimesulide is strictly not recommended. The drug is also contraindicated during breastfeeding.

Nabumethon (Sinmeton)

Release form: tablets of 500 and 750 mg.

Non-selective COX inhibitor.

A single dose for an adult patient is 500-750-1000 mg during or after meals. In especially 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.
It is not recommended to take during pregnancy and breastfeeding.

Combined non-steroidal anti-inflammatory drugs

There are drugs that contain two or more active substances from the NSAID group, or NSAIDs in combination with vitamins or other drugs. The main ones are listed below.

• Dolaren. Contains 50 mg diclofenac sodium and 500 mg paracetamol. IN this drug the pronounced anti-inflammatory effect of diclofenac is combined with a bright analgesic effect paracetamol. Take the drug orally, 1 tablet 2-3 times a day after meals. The maximum daily dose is 3 tablets.
• Neurodiclovit. Capsules containing 50 mg of diclofenac, vitamin B1 and B6, as well as 0.25 mg of vitamin B12. Here, the analgesic and anti-inflammatory effect of diclofenac is enhanced by B vitamins, which improve metabolism in nerve tissue. The recommended dose of the drug is 1-3 capsules per day in 1-3 doses. Take the drug after meals with a sufficient amount of liquid.
• Olfen-75, produced in the form of an injection solution, in addition to diclofenac in an amount of 75 mg, also contains 20 mg of lidocaine: due to the presence of the latter in the solution, injections of the drug become less painful for the patient.
• Fanigan. Its composition is similar to that of Dolaren: 50 mg of diclofenac sodium and 500 mg of paracetamol. It is recommended to take 1 tablet 2-3 times a day.
• Flamidez. Very interesting, different from others medicinal product. In addition to 50 mg of diclofenac and 500 mg of paracetamol, it also contains 15 mg of serratiopeptidase, which is a proteolytic enzyme and has fibrinolytic, anti-inflammatory and decongestant effects. Available in the form of tablets and gel for topical use. The tablet is taken orally, after meals, with a glass of water. As a rule, 1 tablet is prescribed 1-2 times a day. The maximum daily dose is 3 tablets. The gel is used externally, applying it to the affected area of ​​the skin 3-4 times a day.
• Maxigesik. A drug similar in composition and action to Flamidez, described above. The difference lies in the manufacturing company.
• Diplo-P-Pharmex. The composition of these tablets is similar to that of Dolaren. The dosages are the same.
• Dollar The same.
• Dolex. The same.
• Oksalgin-DP. The same.
• Cynepar. The same.
• Dilocaine. Like Olfen-75, it contains diclofenac sodium and lidocaine, but both active ingredients are in half the dosage. Accordingly, it is weaker in action.
• Dolaren gel. Contains diclofenac sodium, menthol, linseed oil and methyl salicylate. All these components, to one degree or another, have an anti-inflammatory effect and potentiate each other’s 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 tizanidine. This drug successfully combines the anti-inflammatory and analgesic effects of nimesulide with the muscle relaxant (muscle relaxing) effect of tizanidine. It is used for acute pain caused by spasm of skeletal muscles (popularly - when the roots are pinched). Take the drug orally after meals with plenty of liquid. The recommended dose is 2 tablets per day in 2 divided doses. The maximum duration of treatment is 2 weeks.
• Nizalid. Like nimide forte, it contains nimesulide and tizanidine in similar dosages. The recommended doses are the same.
• Alit. Soluble tablets containing 100 mg of nimesulide and 20 mg of dicycloverine, which is a muscle relaxant. Take orally after meals with a glass of liquid. It is recommended to take 1 tablet 2 times a day for no longer than 5 days.
• Nanogan. The composition of this drug and recommended dosages are similar to those of the drug Alit described above.
• Oxygen. The same.

2112 0

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the main drugs used to treat inflammatory diseases joints.

They are prescribed in periodic courses for chronic processes, and, if necessary, for exacerbations of diseases and acute inflammatory processes. NSAIDs exist in various dosage forms - tablets, ointments, and injection solutions. Choice necessary means, dosage and frequency of its use should be carried out by a doctor.

NSAIDs - what is this group of drugs?

The group of NSAIDs is quite extensive and includes various chemical structure drugs. The name “non-steroidal” shows their difference from another large group of anti-inflammatory drugs – corticosteroid hormones.

The common properties of all drugs in this group are their three main effects - anti-inflammatory, analgesic, antipyretic.

This explains another name for this group - non-narcotic analgesics, as well as the enormous breadth of their use. These three effects are expressed differently in each drug, so they cannot be completely interchangeable.

Unfortunately, all NSAID drugs have similar side effects. The most famous of them are the provocation of gastric ulcers, toxicity to the liver and inhibition of hematopoiesis. For this reason, you should not exceed the dosage indicated in the instructions, and also take these drugs if you suspect these diseases.

Abdominal pain cannot be treated with such medications - there is always a risk of worsening your condition. Various dosage forms of NSAIDs have been invented to improve their effectiveness in each specific situation and reduce potential harm for good health.

History of discovery and formation

Application herbal remedies, which have anti-inflammatory, antipyretic and analgesic effects, were described in the works of Hippocrates. But first exact description effect of NSAIDs dates back to the 18th century.

In 1763, the English physician and priest Edward Stone wrote in a letter to the chairman of the London Royal Society that an infusion of willow bark, growing in England, has antipyretic properties, described the recipe for its preparation and the method of use for febrile conditions.

Almost half a century later in France, I. Lear isolated a substance from willow bark that caused it medicinal properties. By analogy with From the Latin name for willow - salix, he called this substance salicin. This was the prototype of modern acetylsalicylic acid, which they learned to produce chemically in 1839.

Industrial production of NSAIDs was established in 1888; the first drug to hit pharmacy shelves was acetylsalicylic acid under trade name Aspirin, produced by Bayer, Germany. She still owns the rights to trademark Aspirin, so other manufacturers produce acetylsalicylic acid under an international nonproprietary name or create their own (for example, Upsarin).

More recent developments have led to the emergence of a number of new drugs. Research continues to this day, and increasingly safe and effective means are being created. Oddly enough, the first hypothesis about the mechanism of action of NSAIDs was formulated only in the 20s of the 20th century. Previously, drugs were used empirically, their dosages were determined by the patient's well-being, and side effects were not well studied.

Pharmacological properties and mechanism of action

Development mechanism inflammatory reaction in the body is quite complex and includes a chain chemical reactions, launching each other. One of the groups of substances involved in the development of inflammation is prostaglandins (they were first isolated from prostate tissue, hence the name). These substances have a dual function - they participate in the formation protective factors gastric mucosa and in the inflammatory process.

Prostaglandin synthesis is carried out by two types of cyclooxygenase enzyme. COX-1 synthesizes “gastric” prostaglandins, and COX-2 synthesizes “inflammatory” ones, and is normally inactive. It is the activity of COX that NSAIDs interfere with. Their main effect - anti-inflammatory - is due to the inhibition of COX-2, and the side effect is a violation protective barrier stomach – inhibition of COX-1.

In addition, NSAIDs interfere quite strongly with cellular metabolism, which is responsible for their analgesic effect - they disrupt the conduction of nerve impulses. This is also the cause of lethargy, as a side effect of taking NSAIDs. There is evidence that these drugs stabilize lysosome membranes, slowing down the release of lytic enzymes.

Entering the human body, these drugs are absorbed mostly in the stomach, and in small quantities from the intestines.

Absorption varies; for new drugs, bioavailability can reach 96%. Enteric-coated drugs (Aspirin Cardio) are absorbed much less well. The presence of food does not affect the absorption of drugs, but since they increase acidity, it is advisable to take them after meals.

The metabolism of NSAIDs occurs in the liver, which is associated with their toxicity to this organ and the impossibility of use in various diseases liver. A small part of the incoming dose of the drug is excreted through the kidneys. Modern developments in the field of NSAIDs are aimed at reducing their effect on COX-1 and hepatotoxicity.

Indications for use - scope of application

The diseases and pathological conditions for which NSAIDs are prescribed are varied. Tablets are prescribed as an antipyretic for infectious and non-communicable diseases, and also as a remedy for headaches, dental, joint, menstrual and other types of pain (except for abdominal pain, if its cause is not clear). In children, suppositories containing NSAIDs are used to relieve fever.

Intramuscular injections of NSAIDs are prescribed as an analgesic and antipyretic for severe patient conditions. They are definitely included lytic mixture– combinations of drugs that allow you to quickly knock down dangerous temperature. Intra-articular injections treat severe joint damage caused by inflammatory diseases.

Ointments are used for local impact on inflamed joints, as well as for diseases of the spine, muscle injuries to relieve pain, swelling and inflammation. Ointments can only be applied to healthy skin. For joint diseases, all three dosage forms can be combined.

The most famous drugs of the group

The very first NSAID to go on sale was acetylsalicylic acid under the brand name Aspirin. This name, despite the fact that it is commercial, is strongly associated with the drug. It is prescribed to reduce fever, relieve headaches, small doses - for improvement rheological properties blood. Rarely used for joint diseases.

Metamizole (Analgin) is no less popular than aspirin. Used to relieve pain of various origins, including joint pain. It is prohibited in many European countries, as it has a strong inhibitory effect on hematopoiesis.

– one of the popular drugs for the treatment of joints. Included in many ointments, available in and. It has a pronounced anti-inflammatory and analgesic effect, and almost does not cause system effect.

Side effects

As with any other medication, there are numerous side effects when taking NSAIDs. The most famous among them is ulcerogenic, i.e. provoking ulcers. It is caused by inhibition of COX-1 and is almost completely absent in selective NSAIDs.

Acid derivatives have an additional ulcerogenic effect due to increased acidity gastric juice. Most NSAIDs are contraindicated in gastritis with increased acidity, peptic ulcer of the stomach and duodenum, GERD.

Another common effect is hepatotoxicity. It can manifest itself as pain and heaviness in the abdomen, digestive disorders, and sometimes short-term icteric syndrome, skin itching, other manifestations of liver damage. For hepatitis, cirrhosis and liver failure NSAIDs are contraindicated.

Inhibition of hematopoiesis, which, if the dosage is constantly exceeded, leads to the development of anemia, in some cases - pancytopenia (lack of all blood elements), impaired immunity, and bleeding. NSAIDs are not prescribed for severe bone marrow diseases and after bone marrow transplantation.

Effects associated with poor health - nausea, weakness, slow reaction, decreased attention, feeling tired, allergic reactions up to asthmatic attacks - occur individually.

Classification of NSAIDs

Today, there are many drugs in the NSAID group, and their classification should help the doctor choose the most suitable drug. This classification contains only international nonproprietary names.

Chemical structure

Based on their chemical structure, non-steroidal anti-inflammatory drugs are classified.

Acids (absorbed in the stomach, increase acidity):

• salicylates:
• pyrazolidines:
• indoleacetic acid derivatives:
• phenylacetic acid derivatives:
• oxicams:
• propionic acid derivatives:

Non-acidic derivatives (do not affect the acidity of gastric juice, are absorbed in the intestine):

• alkanones:
• sulfonamide derivatives:

By impact on COX-1 and COX-2

Non-selective - inhibit both types of enzyme, most of the NSAIDs belong to them.

Selective (coxibs) inhibit COX-2, do not affect COX-1:

• Celecoxib;
• Rofecoxib;
• Valdecoxib;
• Parecoxib;
• Lumiracoxib;
• Etoricoxib.

Selective and non-selective NSAIDs

Most NSAIDs are non-selective because they inhibit both types of COX. Selective NSAIDs- more modern drugs that mainly affect COX-2 and minimally affect COX-1. This reduces the risk of side effects.

However, complete selectivity of drug action has not yet been achieved, and there will always be a risk of side effects.

New generation drugs

The new generation includes not only selective, but also some non-selective NSAIDs, which have pronounced effectiveness, but are less toxic to the liver and hematopoietic system.

New generation non-steroidal anti-inflammatory drugs:

• – has an extended period of validity;
• – has the strongest analgesic effect;
• – extended period of action and pronounced analgesic effect (comparable to morphine);
• Rofecoxib– the most selective drug, approved for patients with gastritis and peptic ulcer without exacerbation.

Non-steroidal anti-inflammatory ointments

Usage NSAID drugs in the form for local use (ointments and gels) has a number of advantages, primarily the absence of a systemic effect and a targeted effect on the site of inflammation. For diseases of the joints they are almost always prescribed. The most popular ointments:

• Indomethacin;

NSAIDs in tablets

The most common dosage form of NSAIDs is tablets. Used to treat various diseases, including articular ones.

Among the advantages, they can be prescribed to treat manifestations of a systemic process involving several joints. The disadvantages include pronounced side effects. The list of NSAID drugs in tablets is quite long, they include:

The most common drugs are in the form of tablets and injections, in the form of injections and tablets (these are all new generation NSAIDs), and ointments based on Diclofenac do not lose their effectiveness. Since arthrosis, unlike arthritis, rarely worsens, the main emphasis in treatment is on maintaining the functional state of the joints.

General application features

Nonsteroidal anti-inflammatory drugs for the treatment of joints are prescribed in courses or as needed, depending on the course of the disease.

The main feature of their use is that there is no need to take several drugs of this group in the same dosage form at the same time (especially tablets), since this increases the side effects, and therapeutic effect remains the same.

It is permissible to use different dosage forms at the same time if necessary. It is important to remember that contraindications to taking NSAIDs are common to most drugs in the group.

NSAIDs remain the most important means for the treatment of joints. They are difficult and sometimes almost impossible to replace by any other means. Modern pharmacology is developing new drugs from this group in order to reduce the risk of their side effects and increase the selectivity of action.

Undoubtedly, the most important mechanism of action of NSAIDs is the ability to inhibit COX, an enzyme that catalyzes the conversion of free polyunsaturated fatty acids (for example, arachidonic acid) into prostaglandins (PGs), as well as other eicosanoids - thromboxanes (TrA2) and prostacyclin (PG-I2) (Fig. 1). It has been proven that prostaglandins have diverse biological activities:

a) are mediators of the inflammatory response: they accumulate at the site of inflammation and cause local vasodilation, edema, exudation, migration of leukocytes and other effects (mainly PG-E2 and PG-I2);

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

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

G) play an important physiological role in protecting the mucous membrane of the gastrointestinal tract(increased secretion of mucus and alkali; preservation of the integrity of endothelial cells inside the microvessels of the mucosa, helping to maintain blood flow in the mucosa; preservation of the integrity of granulocytes and thus maintaining the structural integrity of the mucosa);

d) affect kidney function: cause vasodilation, maintain renal blood flow and glomerular filtration rate, increase renin release, sodium and water excretion, and participate in potassium homeostasis.

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

Note: * – LT-S 4, D 4, E 4 are the main biological components of the slow-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 NSAIDs. The first isoenzyme - COX-1 - controls the production of PGs, which regulate the integrity of the mucous membrane of the gastrointestinal tract, platelet function and renal blood flow, and the second isoenzyme - COX-2 - is involved in the synthesis of PGs during inflammation. Moreover, COX-2 is absent under normal conditions, but is formed under the influence of certain tissue factors that initiate the inflammatory response (cytokines and others). In this regard, it is assumed that the anti-inflammatory effect of NSAIDs is due to inhibition of COX-2, and their undesirable reactions are due to inhibition of COX-1. The ratio of the activity of NSAIDs in terms of blocking COX-1/COX-2 allows us to judge their potential toxicity. The lower this value, the more selective the drug is for COX-2 and, thus, the less toxic. For example, for meloxicam it is 0.33, diclofenac - 2.2, tenoxicam - 15, piroxicam - 33, indomethacin - 107.

The latest data indicate that NSAIDs not only inhibit cyclooxygenase metabolism, but also actively influence the synthesis of PG, associated with the mobilization of Ca in smooth muscles. Thus, butadione inhibits the transformation of cyclic endoperoxides into prostaglandins E2 and F2, and fenamates can also block the reception of these substances in tissues.

An important role in the anti-inflammatory effect of NSAIDs is played by their effect on the metabolism and bioeffects of kinins. In therapeutic doses, indomethacin, ortofen, naproxen, ibuprofen, and acetylsalicylic acid (ASA) reduce the formation of bradykinin by 70-80%. This effect is based on the ability of NSAIDs to provide nonspecific inhibition of the interaction of kallikrein with high molecular weight kininogen. NSAIDs cause chemical modification of the components of the kininogenesis reaction, as a result of which, due to steric hindrances, the complementary interaction of protein molecules is disrupted and effective hydrolysis of high molecular weight kininogen by kallikrein does not occur. A decrease in the formation of bradykinin leads to inhibition of the activation of α-phosphorylase, which leads to a decrease in the synthesis of arachidonic acid and, as a consequence, the manifestation of the effects of its metabolic products shown in Fig. 1.

Equally important is the ability of NSAIDs to block the interaction of bradykinin with tissue receptors, which leads to the restoration of impaired microcirculation, a decrease in capillary overextension, a decrease in the yield of the liquid part of the plasma, its proteins, pro-inflammatory factors and formed elements, which indirectly affects the development of other phases of the inflammatory process. Since the kallikrein-kinin system plays the most important role in the development of acute inflammatory reactions, the greatest effectiveness of NSAIDs is observed in the early stages of inflammation in the presence of a pronounced exudative component.

Of particular importance in the mechanism of anti-inflammatory action of NSAIDs are inhibition of the release of histamine and serotonin, blockade of tissue reactions to these biogenic amines, which play a significant role in the inflammatory process. The intramolecular distance between the reaction centers in the molecule of antiphlogistics (compounds such as butadione) approaches those in the molecule of inflammatory mediators (histamine, serotonin). This gives reason to assume the possibility of competitive interaction of the mentioned NSAIDs with receptors or enzyme systems involved in the processes of synthesis, release and transformation of these substances.

As mentioned above, NSAIDs have a membrane-stabilizing effect. By binding to the G-protein in the cell membrane, antiphlogistics affect the transmission of membrane signals through it, suppress the transport of anions, and influence biological processes dependent on the general mobility of membrane lipids. They realize their membrane-stabilizing effect by increasing the microviscosity of membranes. Penetrating through the cytoplasmic membrane into the cell, NSAIDs also affect the functional state of the membranes of cellular structures, in particular lysosomes, and prevent the proinflammatory effect of hydrolases. Data on quantitative and qualitative features of affinity were obtained individual drugs to the protein and lipid components of biological membranes, which may explain their membrane effect.

One of the mechanisms of damage to cell membranes is free radical oxidation. Free radicals, formed during lipid peroxidation, play an important role in the development of inflammation. Therefore, the inhibition of peroxidation in membranes by NSAIDs can be considered as a manifestation of their anti-inflammatory effect. It should be taken into account that one of the main sources of generation of free radicals is the metabolic reactions of arachidonic acid. Individual metabolites of its cascade cause the accumulation of polymorphonuclear neutrophils and macrophages at the site of inflammation, the activation of which is also accompanied by the formation of free radicals. NSAIDs, by functioning as scavengers of these compounds, offer the possibility of a new approach to the prevention and treatment of tissue damage caused by free radicals.

In recent years, research into the effect of NSAIDs on the cellular mechanisms of the inflammatory response has received significant development. NSAIDs reduce the migration of cells to the site of inflammation and reduce their phlogogenic activity, and the effect on polymorphonuclear neutrophils correlates with inhibition of the lipoxygenase pathway of arachidonic acid oxidation. This alternative pathway for the conversion of arachidonic acid leads to the formation of leukotrienes (LT) (Fig. 1), which meet all the criteria for inflammatory mediators. Benoxaprofen has the ability to influence 5-LOG and block the synthesis of LT.

The effect of NSAIDs on cellular elements has been less studied late stage inflammation - mononuclear cells. Some NSAIDs reduce the migration of monocytes, which produce free radicals and cause tissue destruction. Although important role cellular elements in the development of the inflammatory reaction and the therapeutic effect of anti-inflammatory drugs is undeniable; the mechanism of action of NSAIDs on the migration and function of these cells awaits clarification.

There is an assumption about the release of natural anti-inflammatory substances by NSAIDs from the complex with plasma proteins, which comes from the ability of these drugs to displace lysine from its connection with albumin.