There is practically no such disease in which non-steroidal anti-inflammatory drugs (NSAIDs, NSAIDs) would not be used. This is a huge class of injection tablets and ointments, the ancestor of which is the usual Aspirin. The most common indications for their use are joint diseases, accompanied by pain and inflammation. In our pharmacies, both long-tested, well-known medicines and anti-inflammatory drugs are popular. nonsteroidal drugs new generation.

The era of such drugs began quite a long time ago - since 1829, when salicylic acid was first discovered. Since then, new substances and dosage forms have begun to appear that can eliminate inflammation and pain.

With the creation of Aspirin, NSAIDs were separated into a separate group of non-steroidal anti-inflammatory drugs. Their name was determined by the fact that they do not contain hormones (steroids) in their composition, and have fewer pronounced side effects than steroid ones.

Despite the fact that in our country most NSAIDs can be bought in pharmacies without a prescription, there are some points that you need to know about. Especially for those people who are thinking about what is better to choose - drugs offered for years, or modern NSAIDs.

The principle of action of NSAIDs is the effect on the enzyme cyclooxygenase (COX), namely on its two varieties:

1. COX-1 is a protective enzyme of the gastric mucosa, protecting it from acidic contents.
2. COX-2 is an inducible, that is, synthesized enzyme that is produced in response to inflammation, or damage. Thanks to him, the inflammatory process is played out in the body.

Since non-steroids of the first generation are non-selective, that is, they act on both COX-1 and COX-2, along with the anti-inflammatory effect, they also have strong side effects. It is essential to take these tablets after meals, as they are irritating to the stomach and can lead to erosions and ulcers. If you already have gastric ulcers, you need to take them with proton pump inhibitors (Omeprazole, Nexium, Controloc, etc.), which protect the stomach.

Time does not stand still, non-steroids are developing, and are becoming more selective for COX-2. Now at the moment there are drugs that selectively affect the COX-2 enzyme, on which inflammation depends, without affecting COX-1, that is, without damaging the gastric mucosa.

About a quarter of a century ago, there were only eight groups of NSAIDs, but today there are more than fifteen. Having gained wide popularity, non-steroidal pills quickly replaced the opioid analgesic groups of analgesics.

Today, there are two generations of non-steroidal anti-inflammatory drugs. First generation - NSAID drugs, mostly non-selective.

These include:

• Aspirin;
• Citramon;
• Naproxen;
• Voltaren;
• Nurofen;
• Butadion and many others.

New generation non-steroidal anti-inflammatory drugs are safer in terms of side effects, and they have a greater ability to relieve pain.

These are such selective non-steroids as:

• Nimesil;
• Nise;
• Nimesulide;
• Celebrex;
• Indomethaxin.

This is not a complete list and not the only classification of new generation NSAIDs. There is their division into non-acid and acid derivatives.

Among the latest generation of NSAIDs, the most innovative drugs are oxicams. These are non-steroidal anti-inflammatory drugs of a new generation of acid drugs that affect the body much longer and brighter than others.

This includes:

• Lornoxicam;
• Piroxicam;
• Meloxicam;
• Tenoxicam.

The acid group of drugs also includes the following series of non-steroids:

Non-acidic, that is, drugs that do not affect the gastric mucosa, include NSAIDs of a new generation of the sulfonamide group. Representatives of this group are Nimesulide, Rofecoxib, Celecoxib.

A new generation of NSAIDs has gained wide use and popularity due to its ability not only to relieve pain, but also to have an excellent antipyretic effect. The drugs stop the inflammatory process, prevent the development of the disease, so they are prescribed for:

• Diseases of the musculoskeletal tissue. Non-steroids are used to treat injuries, wounds, bruises. They are indispensable for arthrosis, arthritis and other rheumatic diseases. Also, with hernias of the intervertebral discs and myositis, the agents have an anti-inflammatory effect.
• Severe pain syndromes. They are successfully used in the postoperative period, with biliary and renal colic. Tablets have a positive effect on headaches, gynecological pain, successfully relieve pain in migraines.
• The risk of blood clots. Since non-steroids are antiplatelet, that is, blood thinners, they are prescribed for ischemia, and for the prevention of strokes and heart attacks.
• high temperature. These pills and injections are the first antipyretic for adults and children. They are recommended to be used even in febrile conditions.

Means are also used for gout and intestinal obstruction. In case of bronchial asthma, it is not recommended to use NVPP on its own, a preliminary consultation with a doctor is necessary.

Unlike non-selective anti-inflammatory drugs, new generation NSAIDs do not irritate the gastrointestinal system of the body. Their use in the presence of stomach ulcers and duodenum does not lead to exacerbation and bleeding.

However, their long-term use can cause a number of undesirable effects, such as:

• increased fatigue;
• dizziness;
• dyspnea;
• drowsiness;
• destabilization of blood pressure.
• the appearance of protein in the urine;
• indigestion;

Also, with prolonged use, allergic manifestations are possible, even if susceptibility to any substances was not previously observed.

Non-selective non-steroids such as Ibuprofen, Paracetamol or Diclofenac have greater hepatotoxicity. They have a very strong effect on the liver, especially Paracetamol.

In Europe, where all NSAIDs are prescription drugs, over-the-counter Paracetamol (taken as a pain reliever up to 6 tablets per day) is in wide use. There appeared such medical concept, as "paracetamol liver damage", that is, cirrhosis while taking this medication.

A few years ago, a scandal broke out abroad about the influence of modern non-steroids - coxibs on the cardiovascular system. But our scientists did not share the concerns of foreign colleagues. The Russian Association of Rheumatologists acted as an opponent to Western cardiologists and proved that the risk of cardiac complications while taking new generation NSAIDs is minimal.

It is absolutely impossible to use most anti-inflammatory non-steroids during pregnancy, especially in the third trimester. Some of them may be prescribed by a doctor in the first half of pregnancy with special indications.

By analogy with antibiotics, NSAIDs of the new generation should not be taken in too short courses (drank 2-3 days and stopped). This will be harmful, because in the case of antibiotics, the temperature will go away, but the pathological flora will acquire resistance (resistance). The same is with non-steroids - they must be taken for at least 5-7 days, since the pain may go away, but this does not mean that the person has recovered. The anti-inflammatory effect occurs a little later than the anesthetic and proceeds more slowly.

1. Never combine non-steroids from different groups. If you take one pill in the morning for pain, and then another, their beneficial effect is not summed up, and does not increase. And side effects increase in geometric progression. It is especially impossible to combine cardiac Aspirin (Aspirin-Cardio, Cardiomagnyl) and other NSAIDs. In this situation, there is a danger of a heart attack, as the action of aspirin, which thins the blood, is blocked.
2. If a joint hurts, it is better to start with ointments, for example, based on ibuprofen. They need to be applied 3-4 times a day, especially at night, and rubbed intensively into the sore spot. You can do self-massage of a sore spot with ointment.

The main condition is peace. If you continue to actively work or play sports during the treatment, then the effect of the use of drugs will be very small.

The best drugs

Arriving at the pharmacy, each person thinks about which non-steroidal anti-inflammatory drugs to choose, especially if he came without a doctor's prescription. The choice is huge - non-steroids are available in ampoules, tablets, capsules, in the form of ointments and gels.

Tablets - derivatives of acids have the greatest anti-inflammatory effect.

A good analgesic effect in diseases of the musculoskeletal tissue is possessed by:

• Ketoprofen;
• Voltaren or Diclofenac;
• Indomethacin;
• Xefocam or Lornoxicam.

But the most powerful drugs against pain and inflammation are the newest selective NSAIDs - coxibs, which have the fewest side effects. The best non-steroidal anti-inflammatory drugs in this series are Arcoxia, Nise, Movalis, Celecoxib, Xefokam, Etoricoxib.

Xefocam

The analogue of the remedy is Lornoxicam, Rapid. The active substance is xefocam. Effective medicine with a pronounced anti-inflammatory effect. Does not affect heart rate, blood pressure and respiratory rate.

Available in the form:

• tablets;
• injections.

For elderly patients, a special dosage is not required in the absence of renal insufficiency. In case of kidney disease, the dose must be reduced, since the substance is excreted by these organs.

With excessive duration of treatment, manifestations in the form of conjunctivitis, rhinitis and shortness of breath are possible. In asthma, it is used with caution, since an allergic reaction in the form of bronchospasm is possible. With the introduction of an injection intramuscularly, soreness and hyperemia at the injection site are possible.

Arcoxia or its only analogue, Exinev, is a drug used in acute gouty arthritis, rheumatoid-type osteoarthritis, and in the treatment of postoperative conditions associated with pain. Available in the form of tablets for oral administration.

The active substance of this drug is etoricoxib, which is the most modern and safe substance among selective COX-2 inhibitors. The tool perfectly relieves pain, and begins to act on the focus of pain after 20-25 minutes. The active substance of the drug is absorbed from the bloodstream and has a high bioavailability (100%). It is excreted in the urine unchanged.

Nimesulide

Most specialists in sports traumatology distinguish such a non-steroid as Nise or its analogues Nimesil or Nimulide. There are many names, but they have one active substance - nimesulide. This medicine is quite cheap, and occupies one of the first places in sales.

This is a good pain reliever, but Nimesulide-based products cannot be used in children under 12 years of age, as there is a high probability of allergic reactions.

Available as:

• powders;
• suspensions;
• gels;
• tablets.

It is used in the treatment of arthritis, arthrosis, ankylosing spondylitis, sinusitis, lumbago, and pains of various localization.

Movalis is much more selective for COX-2 than Nise, and therefore has even fewer side effects in relation to the stomach.

Release form:

• candles;
• pills;
• injections.

With prolonged use, the risk of developing cardiac thrombosis, heart attacks, angina pectoris is increased. Therefore, people with a predisposition to these diseases need to be careful in their use. It is also not recommended for women planning a pregnancy, as it affects fertility. It is excreted in the form of metabolites, mainly with urine and feces.

Celecoxib

In the group with the most proven base in terms of safety - NSAIDs of the new generation Celecoxib. It was the first drug from the group of selective coxibs, combining the three strengths of this class - the ability to reduce pain, inflammation, and fairly high safety. Release form - capsules of 100 and 200 mg.

The active ingredient celecoxib selectively acts on COX-2 without affecting the gastric mucosa. Rapidly absorbed into the blood highest concentration the substance reaches after 3 hours, but simultaneous intake with fatty foods can slow down the absorption of the drug.

Celecoxib is prescribed for soriatic and rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. Not assigned this remedy with liver and kidney failure.

Rofecoxib

The main substance rofecoxib effectively helps to restore the motor function of the joints, quickly relieving inflammation.

Available as:

• injection solutions;
• tablets;
• candles;
• gel.

The substance is a highly selective inhibitor of cyclooxygenase 2, after administration it is rapidly absorbed by the gastrointestinal tract. The substance reaches its maximum concentration in the blood after 2 hours. It is excreted mainly in the form of inactive metabolites by the kidneys and intestines.

The result of long-term use may be disorders of the nervous system - sleep disturbance, dizziness, confusion. Treatment is recommended to start with injections, then switch to tablets and external agents.

When choosing any NVPS, one should be guided not only by the price and their modernity, but also take into account the fact that all such drugs have their own contraindications. Therefore, you should not self-medicate, it is best if they are prescribed by a doctor, taking into account age and a history of diseases. It should be remembered that the thoughtless use of drugs may not only not bring relief, but also force a person to treat many complications.

Non-steroidal anti-inflammatory drugs, which are briefly called NSAIDs or NSAIDs (means) are widely used throughout the world. In the United States, where statistics cover all branches of life, it was estimated that every year American doctors write more than 70 million prescriptions for NSAIDs. Americans drink, inject, and smear more than 30 billion doses of non-steroidal anti-inflammatory drugs a year. It is unlikely that our compatriots are lagging behind them.

Despite their popularity, most NSAIDs are distinguished by high safety and extremely low toxicity. Even when used in high doses, complications are extremely unlikely. What are these miraculous remedies?

Non-steroidal anti-inflammatory drugs are large group drugs that have three effects at once:

• painkillers;
• antipyretic;
• anti-inflammatory.

The term "non-steroidal" distinguishes these drugs from steroids, i.e. hormonal drugs, which also have anti-inflammatory effects.

The property that favorably distinguishes NSAIDs from other analgesics is the absence of addiction with prolonged use.

Excursion into history

The "roots" of non-steroidal anti-inflammatory drugs go back to the distant past. Hippocrates, who lived in 460-377. BC, reported the use of willow bark for pain relief. A little later, in the 30s BC. Celsius confirmed his words and stated that willow bark perfectly softens the signs of inflammation.

The next mention of the analgesic cortex is found only in 1763. And only in 1827, chemists were able to isolate from the willow extract the very substance that became famous in the time of Hippocrates. The active ingredient in willow bark turned out to be the glycoside salicin, a precursor to non-steroidal anti-inflammatory drugs. From 1.5 kg of bark, scientists received 30 g of purified salicin.

In 1869, for the first time, a more effective derivative of salicin, salicylic acid, was obtained. It soon became clear that it damages the gastric mucosa, and scientists began an active search for new substances. In 1897, the German chemist Felix Hoffmann and the Bayer company ushered in a new era in pharmacology by converting the toxic salicylic acid into acetylsalicylic acid, which was named Aspirin.

For a long time, aspirin remained the first and only representative of the NSAID group. Since 1950, pharmacologists began to synthesize more and more new drugs, each of which was more effective and safer than the previous one.

How do NSAIDs work?

Non-steroidal anti-inflammatory drugs block the production of substances called prostaglandins. They are directly involved in the development of pain, inflammation, fever, muscle cramps. Most NSAIDs non-selectively (non-selectively) block two different enzymes that are required for prostaglandin production. They are called cyclooxygenase - COX-1 and COX-2.

The anti-inflammatory effect of non-steroidal anti-inflammatory drugs is largely due to:

• a decrease in vascular permeability and an improvement in microcirculation in them;
• a decrease in the release from cells of special substances that stimulate inflammation - inflammatory mediators.

In addition, NSAIDs block energy processes in the focus of inflammation, thereby depriving it of "fuel". Analgesic (pain-relieving) action develops as a result of a decrease in the inflammatory process.

Serious disadvantage

It's time to talk about one of the most serious disadvantages of non-steroidal anti-inflammatory drugs. The fact is that COX-1, in addition to participating in the production of harmful prostaglandins, also plays a positive role. It is involved in the synthesis of prostaglandin, which prevents the destruction of the gastric mucosa under the action of its own hydrochloric acid. When non-selective COX-1 and COX-2 inhibitors begin to work, they completely block prostaglandins - and "harmful" causing inflammation, and "useful", protecting the stomach. So non-steroidal anti-inflammatory drugs provoke the development of gastric and duodenal ulcers, as well as internal bleeding.

But there are among the family of NSAIDs and special preparations. These are the most modern tablets that can selectively block COX-2. Cyclooxygenase type 2 is an enzyme that is involved only in inflammation and does not carry any additional load. Therefore, blocking it is not fraught with unpleasant consequences. Selective blockers COX-2s do not cause gastrointestinal problems and are safer than their predecessors.

Nonsteroidal anti-inflammatory drugs and fever

NSAIDs have a completely unique property that sets them apart from other drugs. They have an antipyretic effect and can be used to treat fever. To understand how they work in this capacity, you should remember why the body temperature rises.

Fever develops due to an increase in the level of prostaglandin E2, which changes the so-called firing rate of neurons (activity) within the hypothalamus. Namely, the hypothalamus - a small area in the diencephalon - controls thermoregulation.

Antipyretic non-steroidal anti-inflammatory drugs, also called antipyretics, inhibit the COX enzyme. This leads to inhibition of prostaglandin production, which as a result contributes to the inhibition of neuronal activity in the hypothalamus.

By the way, it was found that ibuprofen has the most pronounced antipyretic properties. It outperformed its closest competitor, paracetamol, in this regard.

Classification of non-steroidal anti-inflammatory drugs

And now let's try to figure out what kind of drugs belong to non-steroidal anti-inflammatory drugs.

Today, several dozen drugs of this group are known, but far from all of them are registered and used in Russia. We will consider only those medicines that can be bought in domestic pharmacies. NSAIDs are classified according to chemical structure and mechanism of action. In order not to frighten the reader with complex terms, we present a simplified version of the classification, in which we present only the most famous names.

So, the entire list of non-steroidal anti-inflammatory drugs is divided into several subgroups.

Salicylates

The most experienced group, with which the history of NSAIDs began. The only salicylate that is still used today is acetylsalicylic acid, or Aspirin.

Propionic acid derivatives

These include some of the most popular non-steroidal anti-inflammatory drugs, in particular drugs:

• ibuprofen;
• naproxen;
• ketoprofen and some other medicines.

Acetic acid derivatives

Acetic acid derivatives are no less famous: indomethacin, ketorolac, diclofenac, aceclofenac and others.

Selective COX-2 inhibitors

The safest non-steroidal anti-inflammatory drugs include seven new drugs of the latest generation, but only two of them are registered in Russia. Remember their international names are celecoxib and rofecoxib.

Other non-steroidal anti-inflammatory

Separate subgroups include piroxicam, meloxicam, mefenamic acid, nimesulide.

Paracetamol has very weak anti-inflammatory activity. It mainly blocks COX-2 in the central nervous system and has an analgesic, as well as a moderate antipyretic effect.

When are NSAIDs used?

Typically, NSAIDs are used to treat acute or chronic inflammation accompanied by pain.

We list the diseases in which non-steroidal anti-inflammatory drugs are used:

• arthrosis;
• moderate pain due to inflammation or soft tissue injury;
• osteochondrosis;
• lower back pain;
• headache;
• acute gout;
• dysmenorrhea (menstrual pain);
• bone pain caused by metastases;
• postoperative pain;
• pain in Parkinson's disease;
• fever (increased body temperature);
• intestinal obstruction;
• renal colic.

In addition, non-steroidal anti-inflammatory drugs are used to treat children whose ductus arteriosus does not close within 24 hours of birth.

This amazing aspirin!

Aspirin can be safely attributed to the drugs that surprised the whole world. The most common non-steroidal anti-inflammatory pills that have been used to reduce fever and treat migraine have shown an unusual side effect. It turned out that by blocking COX-1, aspirin at the same time inhibits the synthesis of thromboxane A2, a substance that increases blood clotting. Some scientists suggest that there are other mechanisms for the effect of aspirin on blood viscosity. However, for millions of patients with hypertension, angina pectoris, coronary heart disease and other cardiovascular diseases, this is not so significant. For them, it is much more important that aspirin in low doses helps prevent cardiovascular disasters - heart attack and stroke.

Most experts recommend taking low-dose cardiac aspirin to prevent myocardial infarction and stroke in men aged 45–79 and women aged 55–79. The dose of aspirin is usually prescribed by a doctor: as a rule, it ranges from 100 to 300 mg per day.

A few years ago, scientists discovered that aspirin reduces the overall risk of developing cancer and mortality from them. This effect is especially true for rectal cancer. American doctors recommend that their patients take aspirin specifically to prevent the development of colorectal cancer. In their opinion, the risk of side effects due to long-term treatment with aspirin is still lower than oncological. By the way, let's take a closer look at the side effects of non-steroidal anti-inflammatory drugs.

Cardiac risks of non-steroidal anti-inflammatory drugs

Aspirin, with its antiplatelet effect, stands out from the orderly row of fellows in the group. The vast majority of non-steroidal anti-inflammatory drugs, including modern COX-2 inhibitors, increase the risk of myocardial infarction and stroke. Cardiologists warn that patients who have recently experienced a heart attack should stop taking NSAIDs. According to statistics, the use of these drugs almost 10 times increases the likelihood of developing unstable angina. According to research data, naproxen is considered the least dangerous from this point of view.

On July 9, 2015, the FDA, the most authoritative American drug quality control organization, issued an official warning. It talks about an increased risk of stroke and heart attack in patients using non-steroidal anti-inflammatory drugs. Of course, aspirin is a happy exception to this axiom.

The effect of non-steroidal anti-inflammatory drugs on the stomach

Another known side effect of NSAIDs is gastrointestinal. We have already said that he has close ties with pharmacological action all non-selective inhibitors of COX-1 and COX-2. However, NSAIDs not only reduce prostaglandin levels and thereby deprive the gastric mucosa of protection. Drug molecules themselves behave aggressively towards the mucous membranes of the gastrointestinal tract.

Against the background of treatment with non-steroidal anti-inflammatory drugs, nausea, vomiting, dyspepsia, diarrhea, stomach ulcers, including those accompanied by bleeding, may occur. Gastrointestinal side effects of NSAIDs develop regardless of how the drug enters the body: oral in the form of tablets, injections in the form of injections or rectal suppositories.

The longer the treatment lasts and the higher the dosage of NSAIDs, the higher the risk of developing peptic ulcer. To minimize the likelihood of it occurring, it makes sense to take the lowest effective dose for the shortest period.

Recent studies show that more than 50% of people taking non-steroidal anti-inflammatory drugs, the lining of the small intestine is still damaged.

Scientists note that drugs of the NSAID group affect the gastric mucosa in different ways. So, the most dangerous drugs for the stomach and intestines are indomethacin, ketoprofen and piroxicam. And among the most harmless in this regard are ibuprofen and diclofenac.

Separately, I would like to say about enteric coatings that cover non-steroidal anti-inflammatory tablets. Manufacturers claim that this coating helps to reduce or completely eliminate the risk of gastrointestinal complications of NSAIDs. However, research and clinical practice show that such protection does not actually work. Much more effectively, the likelihood of damage to the gastric mucosa reduces the simultaneous use of drugs that block the production of hydrochloric acid. Proton pump inhibitors - omeprazole, lansoprazole, esomeprazole and others - can somewhat mitigate the damaging effect of drugs from the group of non-steroidal anti-inflammatory drugs.

Say a word about citramone ...

Citramon is the product of a brainstorming session of Soviet pharmacologists. In ancient times, when the assortment of our pharmacies did not number in the thousands of drugs, pharmacists came up with an excellent formula for analgesic-antipyretic. They combined "in one bottle" a complex of a non-steroidal anti-inflammatory drug, an antipyretic and seasoned the combination with caffeine.

The invention turned out to be very successful. Each active ingredient enhanced the effect of each other. Modern pharmacists have somewhat modified the traditional prescription, replacing the antipyretic phenacetin with safer paracetamol. In addition, cocoa and citric acid, which, in fact, gave the name to citramone, were removed from the old version of citramone. The preparation of the XXI century contains aspirin 0.24 g, paracetamol 0.18 g and caffeine 0.03 g. And despite a slightly modified composition, it still helps with pain.

However, despite the extremely affordable price and very high efficiency, Citramon has its own huge skeleton in the closet. Doctors have long found out and fully proved that it seriously damages the mucosa of the gastrointestinal tract. So seriously that the term "citramone ulcer" even appeared in the literature.

The reason for this apparent aggression is simple: the damaging effect of Aspirin is enhanced by the activity of caffeine, which stimulates the production of hydrochloric acid. As a result, the gastric mucosa, already left without protection of prostaglandins, is exposed to the action of an additional amount of hydrochloric acid. Moreover, it is produced not only in response to food intake, as it should be, but also immediately after the absorption of Citramon into the blood.

We add that "citramone", or as they are sometimes called, "aspirin ulcers" are large. Sometimes they do not "grow" to gigantic, but they take in quantity, settling in whole groups in different parts of the stomach.

The moral of this digression is simple: don't go overboard with Citramon despite all its benefits. The consequences can be too severe.

NSAIDs and… sex

In 2005, in the piggy bank of unpleasant side effects of non-steroidal anti-inflammatory drugs arrived. Finnish scientists conducted a study that showed that long-term use of NSAIDs (over 3 months) increases the risk of erectile dysfunction. Recall that under this term, doctors mean erectile dysfunction, popularly called impotence. Then urologists and andrologists were consoled by the not very high quality of this experiment: the effect of drugs on sexual function was evaluated only on the basis of the man's personal feelings and was not verified by specialists.

However, in 2011, another study was published in the authoritative Journal of Urology. It also showed an association between treatment with non-steroidal anti-inflammatory drugs and erectile dysfunction. However, doctors argue that it is too early to draw final conclusions regarding the effect of NSAIDs on sexual function. In the meantime, scientists are looking for evidence, it is still better for men to refrain from long-term treatment with non-steroidal anti-inflammatory drugs.

Other side effects of NSAIDs

With the serious troubles that threaten treatment with non-steroidal anti-inflammatory drugs, we figured it out. Let's move on to less common adverse events.

Impaired kidney function

The use of NSAIDs is also associated with a relatively high level of renal side effects. Prostaglandins are involved in the expansion of blood vessels in the renal glomeruli, which allows you to maintain normal filtration in the kidneys. When the level of prostaglandins falls - and it is on this effect that the action of non-steroidal anti-inflammatory drugs is based - the work of the kidneys may be disturbed.

People with kidney disease are, of course, most at risk for kidney side effects.

photosensitivity

Quite often, long-term treatment with non-steroidal anti-inflammatory drugs is accompanied by increased photosensitivity. It is noted that piroxicam and diclofenac are more involved in this side effect.

People taking anti-inflammatory drugs may react to the sun's rays with skin redness, a rash, or other skin reactions.

Hypersensitivity reactions

Non-steroidal anti-inflammatory drugs are also "famous" for allergic reactions. They can manifest as a rash, photosensitivity, itching, Quincke's edema, and even anaphylactic shock. True, the latter effect is among the extremely rare and therefore should not frighten potential patients.

In addition, taking NSAIDs may be accompanied by headache, dizziness, drowsiness, bronchospasm. Rarely, ibuprofen causes irritable bowel syndrome.

Non-steroidal anti-inflammatory during pregnancy

Quite often, pregnant women face the issue of anesthesia. Can expectant mothers use NSAIDs? Unfortunately no.

Despite the fact that non-steroidal anti-inflammatory drugs do not have a teratogenic effect, that is, they do not cause gross malformations in a child, they can still do harm.

So, there is evidence that suggests a possible premature closure of the ductus arteriosus in the fetus if his mother took NSAIDs during pregnancy. In addition, some studies show an association between NSAID use and preterm birth.

Nevertheless, selected drugs are still used during pregnancy. For example, Aspirin is often given with heparin to women who have antiphospholipid antibodies during pregnancy. Recently, the old and rather rarely used Indomethacin has gained particular fame as a medicine for the treatment of pregnancy pathologies. It began to be used in obstetrics for polyhydramnios and the threat of premature birth. However, in France, the Ministry of Health issued an official order banning the use of non-steroidal anti-inflammatory drugs, including aspirin, after the sixth month of pregnancy.

NSAIDs: accept or refuse?

When do NSAIDs become a necessity, and when should they be abandoned outright? Let's look at all possible situations.

NSAIDs needed	Take NSAIDs with caution	Better to avoid NSAIDs
If you have osteoarthritis that is accompanied by pain, inflammation of the joints and impaired mobility that is not relieved by other drugs or paracetamol If you have severe rheumatoid arthritis pain syndrome and inflammatory process If you have a moderate headache, joint or muscle injury (NSAIDs are prescribed only for a short time. It is possible to start pain relief with paracetamol) If you have mild chronic pain that is not related to osteoarthritis, such as in your back.	If you often suffer from indigestion If you are over 50 years of age or have a history of gastrointestinal disease and/or a family history of early heart disease If you smoke, have high cholesterol or high blood pressure, or have kidney disease if you are taking steroids or blood thinners (clopidogrel, warfarin) If you have been taking NSAIDs to relieve symptoms of osteoarthritis for many years, especially if you have had gastrointestinal diseases	if you have ever had a stomach ulcer or stomach bleeding If you suffer from coronary artery disease or any other heart disease If you suffer from severe hypertension If you have chronic kidney disease If you have ever had a myocardial infarction If you are taking aspirin to prevent a heart attack or stroke If you are pregnant (especially in the third trimester)

NSAIDs in faces

We already know the strengths and weak sides NSAIDs. And now let's figure out which anti-inflammatory drugs are best used for pain, which ones for inflammation, and which ones for fever and colds.

Acetylsalicylic acid

The first NSAID to be released, acetylsalicylic acid, is still widely used today. As a rule, it is used:

• to lower body temperature.

  Please note that acetylsalicylic acid is not prescribed to children under the age of 15 years. This is due to the fact that with childhood fever against the background of viral diseases, the drug significantly increases the risk of developing Reye's syndrome, a rare liver disease that poses a threat to life.

  The adult dosage of acetylsalicylic acid as an antipyretic is 500 mg. Tablets are taken only when the temperature rises.

• as an antiplatelet agent for the prevention of cardiovascular accidents. The dose of cardioaspirin can range from 75 mg to 300 mg per day.

In an antipyretic dosage, acetylsalicylic acid can be bought under the names Aspirin (manufacturer and owner trademark German corporation Bayer). Domestic enterprises produce very inexpensive tablets, which are called Acetylsalicylic acid. In addition, the French company Bristol Myers produces effervescent tablets Upsarin Upsa.

Cardioaspirin has many names and formulations, including Aspirin Cardio, Aspinat, Aspicor, CardiASK, Thrombo ACC, and others.

Ibuprofen

Ibuprofen combines relative safety and the ability to effectively reduce fever and pain, so preparations based on it are sold without a prescription. As an antipyretic, ibuprofen is also used for newborns. It has been proven to reduce fever better than other non-steroidal anti-inflammatory drugs.

In addition, ibuprofen is one of the most popular over-the-counter analgesics. As an anti-inflammatory drug, it is not prescribed so often, however, the drug is quite popular in rheumatology: it is used to treat rheumatoid arthritis, osteoarthritis and other joint diseases.

The most popular brand names for ibuprofen include Ibuprom, Nurofen, MIG 200 and MIG 400.

Naproxen

Naproxen is prohibited for use in children and adolescents under 16 years of age, as well as in adults suffering from severe heart failure. Most often, non-steroidal anti-inflammatory drugs naproxen are used as painkillers for headache, dental, periodic, joint and other types of pain.

In Russian pharmacies, naproxen is sold under the names Nalgezin, Naprobene, Pronaxen, Sanaprox and others.

Ketoprofen

Ketoprofen preparations are distinguished by anti-inflammatory activity. It is widely used to relieve pain and reduce inflammation in rheumatic diseases. Ketoprofen is available in the form of tablets, ointments, suppositories and injections. Popular drugs include the Ketonal line manufactured by the Slovak company Lek. German joint gel Fastum is also famous.

Indomethacin

One of the outdated non-steroidal anti-inflammatory drugs, Indomethacin is losing ground every day. It has modest analgesic properties and moderate anti-inflammatory activity. In recent years, the name "indomethacin" has been heard more and more often in obstetrics - its ability to relax the muscles of the uterus has been proven.

Ketorolac

A unique non-steroidal anti-inflammatory drug with a pronounced analgesic effect. The analgesic abilities of ketorolac are comparable to those of some weak narcotic analgesics. Negative side the drug is its insecurity: it can cause gastric bleeding, provoke stomach ulcers, as well as liver failure. Therefore, you can use ketorolac for a limited period of time.

In pharmacies, Ketorolac is sold under the names Ketanov, Ketalgin, Ketorol, Toradol and others.

Diclofenac

Diclofenac is the most popular non-steroidal anti-inflammatory drug, the "gold standard" in the treatment of osteoarthritis, rheumatism and other joint pathologies. It has excellent anti-inflammatory and analgesic properties and is therefore widely used in rheumatology.

Diclofenac has many forms of release: tablets, capsules, ointments, gels, suppositories, ampoules. In addition, diclofenac patches have been developed to provide a long-lasting effect.

There are a lot of analogues of diclofenac, and we will list only the most famous of them:

• Voltaren - original drug Swiss company Novartis. Differs in high quality and the same high price;
• Diklak - ruler German drugs Geksal firms, combining both reasonable cost and decent quality;
• Dicloberl made in Germany, Berlin Chemie company;
• Naklofen - Slovak drugs from KRKA.

In addition, the domestic industry produces many inexpensive non-steroidal anti-inflammatory drugs with diclofenac in the form of tablets, ointments and injections.

Celecoxib

A modern non-steroidal inflammatory drug that selectively blocks COX-2. It has a high safety profile and pronounced anti-inflammatory activity. It is used for rheumatoid arthritis and other joint diseases.

The original celecoxib is sold under the name Celebrex (Pfizer). In addition, pharmacies have more affordable Dilaxa, Coxib and Celecoxib.

Meloxicam

A popular NSAID used in rheumatology. It has a rather mild effect on the digestive tract, so it is often preferred for the treatment of patients with a history of diseases of the stomach or intestines.

Assign meloxicam in tablets or injections. Meloxicam preparations Melbek, Melox, Meloflam, Movalis, Exen-Sanovel and others.

Nimesulide

Most often, nimesulide is used as a mild analgesic, and sometimes as an antipyretic. Until recently, pharmacies sold a children's form of nimesulide, which was used to reduce fever, but today it is strictly prohibited for children under 12 years of age.

Trade names of nimesulide: Aponil, Nise, Nimesil (German original drug in the form of a powder for preparing a solution for internal use) and others.

Finally, we will devote a couple of lines to Mefenamic acid. It is sometimes used as an antipyretic, but it is significantly inferior in effectiveness to other non-steroidal anti-inflammatory drugs.

The world of NSAIDs is truly amazing in its diversity. And despite the side effects, these drugs are rightfully among the most important and necessary, which can neither be replaced nor bypassed. It remains only to give praise to the tireless pharmacists who continue to create new formulas, and to be treated with ever safer NSAIDs.

Non-steroidal anti-inflammatory drugs- an extensive group of drugs in medicine, prescribed for the relief of pain, lowering the temperature in various diseases. Medicines have not only a pronounced therapeutic effect, but also certain contraindications, side effects.

Non-steroidal anti-inflammatory drugs have a number of contraindications

Classification of NSAIDs

In pharmacology, different signs are used to distribute non-steroidal anti-inflammatory drugs.

By chemical structure

According to the chemical structure and activity, drugs are divided into acidic and non-acidic drugs.

Groups of acid preparations:

• oxicam - Meloxicam, Piroxicam;
• preparations based on indoleacetic acid - Indomethacin, Sulindac;
• drugs that contain propionic acid - Ketoprofen, Ibuprofen;
• salicylates - Aspirin;
• preparations based on phenylacetic acid - Diclofenac, Aceclofenac;
• pyrazolone derivatives - Analgin, Phenylbutazone.

Aspirin belongs to the group of salicylates.

Non-acid agents include alkanones (Nabumeton), sulfonamides (Nimesulide), coxibs (Celecoxib, Rofecoxib).

All non-steroidal drugs have a similar mechanism of action, have a non-specific effect on inflammatory enzymes, therefore, they well eliminate pain of various origins, and cope well with fever during colds and flu. But for each drug, this or that action is somewhat more pronounced than for other drugs of the same group.

According to the principle of general action

According to the mechanism of action, NSAIDs are classified into selective and non-selective drugs.

non-selective NSAIDs

The body produces 2 types of cyclooxygenase enzymes. COX-1 appear only as a response to the inflammatory process, COX-2 protects the walls of the stomach from the influence of negative factors.

Non-selective NSAIDs inhibit the synthesis of COX-1 and COX-2, therefore, they have an extensive list of adverse reactions, this group includes most nonsteroidal drugs.

Indications - high fever, migraine, gynecological and dental diseases, biliary colic, chronic prostatitis. But most often, NSAIDs are prescribed to eliminate the manifestation of problems with joints, muscles - arthritis, arthrosis, myositis, bruises, sprains, fractures. The main contraindications are peptic ulcer, poor blood clotting, kidney and liver pathologies, asthma.

List of popular non-selective NSAIDs

Pharmaceutical companies are constantly trying to reduce the negative impact of NSAIDs on the gastrointestinal tract, so modern non-selective drugs are safe, have a long period of action, which allows you to take drugs once a day.

List of non-selective NSAIDs of the new generation:

1. Movalis is an effective remedy, there are solutions for injections, pills, ointments on sale, the medicine has a powerful antipyretic effect, quickly eliminates pain and signs of inflammation.
2. Xefocam is one of the best remedies for relieving an acute attack of pain, the action of the drug is similar to morphine, but it belongs to non-narcotic drugs. Available in tablets and powder.
3. Nimesulide - tablets and gel with a pronounced anti-inflammatory effect, help well with back and joint pain, the medicine eliminates hyperemia, swelling, signs of the inflammatory process, improves mobility.
4. Aertal - in terms of therapeutic effect, the drug is similar to Diclofenac, but has greater selectivity, is produced in tablets, powder for suspensions, in the form of a cream.

During long-term treatment with NSAIDs, it is necessary to regularly monitor the functioning of the liver, kidneys, and blood counts, this is especially true for elderly patients.

Movalis is an effective non-steroidal agent

selective NSAIDs

Most modern NSAIDs are selective inhibitors, blocking only the inflammatory enzyme, as practice shows, they have a more gentle effect on the gastrointestinal tract, so the risk of ulcers and bleeding is reduced, but the likelihood of blood clots increases. The disadvantage is the high cost.

Selective drugs are more effective than non-selective drugs, the therapeutic effect is observed within 20-30 minutes after taking the medicine, they are successfully practiced in severe joint diseases - infectious non-specific polyarthritis, rheumatoid spondylitis and arthritis, gout, osteoarthritis, osteochondrosis.

List of the best NSAIDs:

1. Celebrex - capsules to eliminate fever, pain and inflammation, significantly reduce the risk of colon cancer. The medicine helps well with arthritis, osteochondrosis.
2. Firocoxib is a highly selective drug in the form of tablets.
3. Rofecoxib - the drug quickly copes with pain, swelling with bursitis, tendonitis, sprains, eliminates fever, headache and toothache of varying degrees of intensity. Produced in the form of tablets, suppositories, solution for injections, gel.

Celebrex is a selective drug

But even drugs that do not affect the stomach should not be taken in the presence of internal bleeding, perforation of the gastrointestinal mucosa, which occurred while taking NSAIDs. Potent medicines are also contraindicated in severe forms of dysfunction of the kidneys, liver, heart, hemocoagulation disorders, aspirin asthma.

NSAIDs are antiplatelet agents, they are prescribed for diseases of the heart and blood vessels - ischemia, angina pectoris, prevention of stroke, heart attack, hypertension.

Non-steroidal anti-inflammatory drugs during pregnancy

NSAIDs have teratogenic properties, can provoke a miscarriage, cause the development of severe pathologies in a newborn, so it is dangerous to take these drugs during pregnancy.

NSAIDs penetrate into breast milk in small quantities, but there is no reliable data on how safe these doses are for children, so doctors recommend refraining from taking these drugs during lactation, or drinking drugs with a short half-life after feeding.

What analgesics can be taken by lactating and pregnant women? Paracetamol, drugs based on ibuprofen can be drunk in the I, II trimester.

NSAIDs can prevent or delay the onset of ovulation, negatively affect human reproductive functions, but how great this risk is has not yet been clinically identified.

NSAIDs for children

Due to the large number of negative reactions, the destructive effect on the gastric mucosa, the ability to thin the blood, most NSAIDs are prohibited for the treatment of children.

Medicines based on nimesulide, ibuprofen and paracetamol, in the form of suppositories and suspensions, are considered safe for children. The main indications are fever, colds, headache, teething.

List of safe NSAIDs for children:

1. Ibuprofen, Nurofen, Ibuklin, Ibufen - drugs help reduce fever, are effective painkillers, adverse reactions are rare, and are used in pediatrics for children older than 3 months.
2. Paracetamol, Panadol, Efferalgan - can be given to children older than 2 months, but these medicines are not recommended to be given to a child in the presence of liver pathologies.
3. Nimesulide, Nise, Nimesil - representatives of the latest generation of NSAIDs, have a long analgesic effect, are used to treat children over 12 years old.

Nimesulide can be given to children over 12 years of age

The most dangerous for children are derivatives of acetylsalicylic acid - Aspirin, Citramon, they should not be taken by patients under 16 years of age. These drugs can provoke the development of Reye's syndrome, the disease is accompanied by encephalopathy and depression of liver function.

How to protect the stomach when taking nonsteroidal drugs?

NSAIDs negatively affect the integrity of the gastric mucosa, which often causes the development of ulcers, erosions, gastritis, and internal bleeding. To avoid the occurrence of such dangerous complications, it is necessary to adhere to certain rules.

How to reduce the negative impact of NSAIDs:

1. It is strictly forbidden to drink alcohol while taking nonsteroidal drugs, otherwise the risk of erosions and ulcers increases significantly.
2. Tablets should not be taken on an empty stomach, you need to drink the medicine during meals, drink plenty of purified water or milk.
3. Be sure to study the interaction of other medicines with NSAIDs in the instructions.
4. During treatment, you must not only strictly observe the dosage, but also follow the regimen, try to take the medicine at the same time.
5. To protect the stomach from the negative effects of NSAIDs, it is necessary to take proton pump inhibitors in parallel with them - Omeprazole, Pantoprazole.

Omeprazole helps to cope with the negative effects of NSAIDs

If you are taking non-steroidal anti-inflammatory drugs long time, it is necessary to do a gastroscopy, take tests for the presence of Helicobacter pylori bacteria - this will help to avoid the development of severe stomach problems.

NSAIDs are the most popular group of medicines in the world, but they must be taken wisely, clearly follow the instructions. If the dosages are not observed, internal bleeding, ulcers may occur, with extreme caution, drugs are prescribed to pregnant lactating women, children, and the elderly.

Rice. one. Metabolism of arachidonic acid

PG have versatile biological activity:

a) are mediators inflammatory response: cause local vasodilation, edema, exudation, migration of leukocytes and other effects (mainly PG-E 2 and PG-I 2);

6) sensitize receptors to mediators of pain (histamine, bradykinin) and mechanical influences, lowering the threshold of pain sensitivity;

in) increase the sensitivity of the hypothalamic centers of thermoregulation to the action of endogenous pyrogens (interleukin-1 and others) formed in the body under the influence of microbes, viruses, toxins (mainly PG-E 2).

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 (COX-1 - English) - controls the production of prostaglandins, which regulates the integrity of the gastrointestinal mucosa, platelet function and renal blood flow, and the second isoenzyme - COX-2 - is involved in the synthesis of prostaglandins during inflammation. Moreover, COX-2 in normal conditions is absent, but is formed under the influence of some tissue factors that initiate an inflammatory reaction (cytokines and others). In this regard, it is assumed that the anti-inflammatory effect of NSAIDs is due to COX-2 inhibition, and their undesirable reactions are due to COX inhibition, the classification of NSAIDs according to selectivity for various forms of cyclooxygenase is presented in. The ratio of the activity of NSAIDs in terms of blocking COX-1 / COX-2 makes it possible to judge their potential toxicity. The smaller this value, the more selective the drug in relation to COX-2 and, thus, less toxic. For example, for meloxicam it is 0.33, diclofenac - 2.2, tenoxicam - 15, piroxicam - 33, indomethacin - 107.

Table 2. Classification of NSAIDs by selectivity for various forms of cyclooxygenase
(Drugs Therapy Perspectives, 2000, with additions)

Other mechanisms of action of NSAIDs

The anti-inflammatory effect may be associated with inhibition of lipid peroxidation, stabilization of lysosome membranes (both of these mechanisms prevent damage to cellular structures), a decrease in the formation of ATP (the energy supply of the inflammatory reaction decreases), inhibition of neutrophil aggregation (the release of inflammatory mediators from them is impaired), inhibition of the production of rheumatoid factor in patients with rheumatoid arthritis. The analgesic effect is to some extent associated with a violation of the conduction of pain impulses in spinal cord ().

Main Effects

Anti-inflammatory effect

NSAIDs suppress predominantly the exudation phase. Most powerful drugs-,, - also act on the proliferation phase (reducing the synthesis of collagen and the associated tissue sclerosis), but weaker than on the exudative phase. NSAIDs have practically no effect on the alteration phase. In terms of anti-inflammatory activity, all NSAIDs are inferior to glucocorticoids., which, by inhibiting the enzyme phospholipase A 2, inhibit the metabolism of phospholipids and disrupt the formation of both prostaglandins and leukotrienes, which are also the most important mediators of inflammation ().

Analgesic effect

To a greater extent, it manifests itself with pains of low and moderate intensity, which are localized in the muscles, joints, tendons, nerve trunks, as well as with headache or toothache. With severe visceral pain, most NSAIDs are less effective and inferior in strength to the analgesic effect of drugs from the morphine group (narcotic analgesics). At the same time, a number of controlled studies have shown a fairly high analgesic activity,,, with colic and postoperative pain. The effectiveness of NSAIDs in renal colic that occurs in patients with urolithiasis is largely associated with inhibition of the production of PG-E 2 in the kidneys, a decrease in renal blood flow and urine formation. This leads to a decrease in pressure in the renal pelvis and ureters above the site of obstruction and provides a long-term analgesic effect. The advantage of NSAIDs over narcotic analgesics is that they do not depress the respiratory center, do not cause euphoria and drug dependence, and with colic, it also matters that they do not have a spasmodic effect.

Antipyretic effect

NSAIDs only work for fever. On the normal temperature bodies do not affect how they differ from "hypothermic" agents (chlorpromazine and others).

Antiaggregatory effect

As a result of inhibition of COX-1 in platelets, the synthesis of the endogenous proaggregant thromboxane is suppressed. It has the strongest and longest antiaggregatory activity, which irreversibly suppresses the ability of a platelet to aggregate for its entire lifespan (7 days). The antiaggregatory effect of other NSAIDs is weaker and reversible. Selective COX-2 inhibitors do not affect platelet aggregation.

Immunosuppressive effect

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

PHARMACOKINETICS

All NSAIDs are well absorbed in the gastrointestinal tract. Almost completely bound to plasma albumin, while displacing some other drugs (see chapter), and in newborns - bilirubin, which can lead to the development of bilirubin encephalopathy. The most dangerous in this respect are salicylates and. Most NSAIDs penetrate well into the synovial fluid of the joints. NSAIDs are metabolized in the liver and excreted through the kidneys.

INDICATIONS FOR USE

1. Rheumatic diseases

Rheumatism (rheumatic fever), rheumatoid arthritis, gouty and psoriatic arthritis, ankylosing spondylitis (Bekhterev's disease), Reiter's syndrome.

It should be borne in mind that in rheumatoid arthritis, NSAIDs have only symptomatic effect without affecting the course of the disease. They are not able to stop the progression of the process, cause remission and prevent the development of joint deformity. At the same time, the relief that NSAIDs bring to patients with rheumatoid arthritis is so significant that none of them can do without these drugs. With large collagenoses (systemic lupus erythematosus, scleroderma, and others), NSAIDs are often ineffective.

2. Non-rheumatic diseases of the musculoskeletal system

Osteoarthritis, myositis, tendovaginitis, trauma (domestic, sports). Often, in these conditions, the use of local dosage forms of NSAIDs (ointments, creams, gels) is effective.

3. Neurological diseases. Neuralgia, sciatica, sciatica, lumbago.

4. Renal, hepatic colic.

5. Pain syndrome various etiologies, including headache and toothache, postoperative pain.

6. Fever(as a rule, at a body temperature above 38.5 ° C).

7. Prevention of arterial thrombosis.

8. Dysmenorrhea.

NSAIDs are used in primary dysmenorrhea to relieve pain associated with an increase in uterine tone due to hyperproduction of PG-F 2a. In addition to the analgesic effect of NSAIDs, they reduce the amount of blood loss.

Good clinical effect noted when using, and especially its sodium salt,,,. NSAIDs are prescribed at the first appearance of pain in a 3-day course or on the eve of menstruation. Adverse reactions, given the short-term use, are rare.

CONTRAINDICATIONS

NSAIDs are contraindicated in erosive and ulcerative lesions of the gastrointestinal tract, especially in the acute stage, severe violations of the liver and kidneys, cytopenias, individual intolerance, pregnancy. If necessary, the safest (but not before childbirth!) Are small doses ().

Currently, a specific syndrome has been identified - NSAID-gastroduodenopathy(). It is only partly associated with the local damaging effect of NSAIDs (most of them are organic acids) on the mucosa and is mainly due to inhibition of the COX-1 isoenzyme as a result of systemic action drugs. Therefore, gastrotoxicity can occur with any route of administration of NSAIDs.

The defeat of the gastric mucosa proceeds in 3 stages:
1) inhibition of the synthesis of prostaglandins in the mucosa;
2) reduction of prostaglandin-mediated production of protective mucus and bicarbonates;
3) the appearance of erosions and ulcers, which may be complicated by bleeding or perforation.

Damage is more often localized in the stomach, mainly in the antrum or prepyloric region. Clinical symptoms in NSAID-gastroduodenopathy are absent in almost 60% of patients, especially the elderly, so the diagnosis is in many cases established with fibrogastroduodenoscopy. At the same time, in many patients presenting with dyspeptic complaints, mucosal damage is not detected. The absence of clinical symptoms in NSAID-gastroduodenopathy is associated with the analgesic effect of drugs. Therefore, patients, especially the elderly, who do not experience adverse effects from the gastrointestinal tract with long-term use of NSAIDs, are considered as a group at an increased risk of developing serious complications of NSAID-gastroduodenopathy (bleeding, severe anemia) and require particularly careful monitoring, including endoscopy (1).

Risk factors for gastrotoxicity: women, age over 60 years, smoking, alcohol abuse, family history of ulcerative disease, concomitant severe cardiovascular disease, concomitant use of glucocorticoids, immunosuppressants, anticoagulants, long-term NSAID therapy, high doses or simultaneous use of two or more NSAIDs. Have the greatest gastrotoxicity, and ().

Methods for improving the tolerability of NSAIDs.

I. Simultaneous administration of drugs protecting the mucous membrane of the gastrointestinal tract.

According to controlled clinical trials, the synthetic analogue of PG-E 2, misoprostol, is highly effective, which can prevent the development of ulcers both in the stomach and in the duodenum (). Combinations of NSAIDs and misoprostol are available (see below).

Table 3 The protective effect of various drugs against NSAID-induced ulcers of the gastrointestinal tract (According to Champion G.D. et al., 1997 () with additions)

+ preventive effect
0 no preventive effect
– effect not specified
* recent data suggest that famotidine is effective at high doses

Inhibitor proton pump Omeprazole has about the same efficacy as misoprostol, but is better tolerated, faster eliminates reflux, pain and digestive disorders.

H 2 -blockers are able to prevent the formation of duodenal ulcers, but, as a rule, are ineffective against gastric ulcers. However, there is evidence that high doses of famotidine (40 mg twice daily) reduce the incidence of both gastric and duodenal ulcers.

Rice. 2. Algorithm for the prevention and treatment of NSAID-gastroduodenopathy.
By Loeb D.S. et al., 1992 () with additions.

The cytoprotective drug sucralfate does not reduce the risk of gastric ulcers, and its effect on duodenal ulcers has not been fully determined.

II. Change of tactics use of NSAIDs , which involves (a) dose reduction; (b) switching to parenteral, rectal or topical administration; (c) taking enteric-soluble dosage forms; (d) use of prodrugs (eg, sulindac). However, due to the fact that NSAID-gastroduodenopathy is not so much a local as a systemic reaction, these approaches do not solve the problem.

III. The use of selective NSAIDs.

As noted above, there are two cyclooxygenase isoenzymes that are blocked by NSAIDs: COX-2, which is responsible for the production of prostaglandins during inflammation, and COX-1, which controls the production of prostaglandins that maintain the integrity of the gastrointestinal mucosa, renal blood flow, and platelet function. Therefore, selective COX-2 inhibitors should cause fewer adverse reactions. The first such drugs are and. Controlled studies conducted in patients with rheumatoid arthritis and osteoarthritis have shown that they are better tolerated than, and, not inferior to them in terms of effectiveness ().

The development of a stomach ulcer in a patient requires the abolition of NSAIDs and the use of antiulcer drugs. Continued use of NSAIDs, for example, in rheumatoid arthritis, is possible only against the background of the parallel administration of misoprostol and regular endoscopic monitoring.

II. NSAIDs can have a direct effect on the renal parenchyma, causing interstitial nephritis(so-called "analgesic nephropathy"). The most dangerous in this regard is phenacetin. Serious damage to the kidneys up to the development of severe renal failure is possible. The development of acute renal failure with the use of NSAIDs as a consequence of severely allergic interstitial nephritis.

Risk factors for nephrotoxicity: age over 65 years, cirrhosis of the liver, previous renal pathology, decrease in circulating blood volume, long-term use of NSAIDs, concomitant use of diuretics.

Hematotoxicity

Most typical for pyrazolidines and pyrazolones. The most formidable complications in their application - aplastic anemia and agranulocytosis.

coagulopathy

NSAIDs inhibit platelet aggregation and have a moderate anticoagulant effect by inhibiting the formation of prothrombin in the liver. As a result, bleeding may develop, more often from the gastrointestinal tract.

Hepatotoxicity

There may be changes in the activity of transaminases and other enzymes. In severe cases - jaundice, hepatitis.

Hypersensitivity reactions (allergies)

Rash, angioedema, anaphylactic shock, Lyell and Stevens-Johnson syndromes, allergic interstitial nephritis. Skin manifestations are more often observed with the use of pyrazolones and pyrazolidins.

Bronchospasm

As a rule, it develops in patients with bronchial asthma and, more often, when taking aspirin. Its causes may be allergic mechanisms, as well as inhibition of the synthesis of PG-E 2, which is an endogenous bronchodilator.

Prolongation of pregnancy and delay in labor

This effect is due to the fact that prostaglandins (PG-E 2 and PG-F 2a ) stimulate the myometrium.

CONTROLS FOR PROLONGED USE

Gastrointestinal tract

Patients should be warned about the symptoms of lesions of the gastrointestinal tract. Every 1-3 months, a fecal occult blood test () should be performed. If possible, periodically conduct fibrogastroduodenoscopy.

Rectal suppositories with NSAIDs should be used in patients who have undergone surgery on the upper gastrointestinal tract, and in patients receiving several drugs at the same time. They should not be used for inflammation of the rectum or anus and after recent anorectal bleeding.

Table 4 Laboratory monitoring for long-term use of NSAIDs

kidneys

It is necessary to monitor the appearance of edema, measure blood pressure, especially in patients with hypertension. Once every 3 weeks, a clinical urine test is performed. Every 1-3 months it is necessary to determine the level of serum creatinine and calculate its clearance.

Liver

With long-term administration of NSAIDs, it is necessary to promptly identify clinical signs of liver damage. Every 1-3 months, liver function should be monitored, transaminase activity should be determined.

hematopoiesis

Along with clinical observation, a clinical blood test should be performed once every 2-3 weeks. Special control is necessary when prescribing pyrazolone and pyrazolidine derivatives ().

RULES OF ADMINISTRATION AND DOSING

Individualization of drug choice

For each patient, the most effective drug with the best tolerance. Moreover, this may be any NSAID, but as an anti-inflammatory it is necessary to prescribe a drug from group I. Sensitivity of patients to NSAIDs even one chemical group can vary widely, so the ineffectiveness of one of the drugs does not mean the ineffectiveness of the group as a whole.

When using NSAIDs in rheumatology, especially when replacing one drug with another, it must be taken into account that the development of the anti-inflammatory effect lags behind the analgesic. The latter is noted in the first hours, while anti-inflammatory - after 10-14 days of regular intake, and when prescribed or oxycams even later - at 2-4 weeks.

Dosage

Any new drug for this patient must be prescribed first. at the lowest dose. With good tolerance after 2-3 days, the daily dose is increased. Therapeutic doses of NSAIDs are in a wide range, and in recent years there has been a tendency to increase single and daily doses of drugs characterized by the best tolerance ( , ), while maintaining restrictions on maximum doses , , , . In some patients, the therapeutic effect is achieved only when using very high doses of NSAIDs.

Time of receipt

With a long course appointment (for example, in rheumatology), NSAIDs are taken after meals. But to get a quick analgesic or antipyretic effect, it is preferable to prescribe them 30 minutes before or 2 hours after a meal with 1/2-1 glass of water. After taking it for 15 minutes, it is advisable not to lie down in order to prevent the development of esophagitis.

The moment of taking NSAIDs can also be determined by the time of maximum severity of the symptoms of the disease (pain, stiffness in the joints), that is, taking into account the chronopharmacology of drugs. In this case, you can deviate from the generally accepted schemes (2-3 times a day) and prescribe NSAIDs at any time of the day, which often allows you to achieve a greater therapeutic effect with a lower daily dose.

With severe morning stiffness, it is advisable to take rapidly absorbed NSAIDs as early as possible (immediately after waking up) or to prescribe long-acting drugs at night. The highest absorption rate in the gastrointestinal tract and, therefore, a faster onset of the effect is possessed by,, water-soluble ("effervescent"),.

Monotherapy

The simultaneous use of two or more NSAIDs is not advisable for the following reasons:
– the effectiveness of such combinations has not been objectively proven;
- in a number similar cases there is a decrease in the concentration of drugs in the blood (for example, reduces the concentration, , , , ), which leads to a weakening of the effect;
- the risk of developing unwanted reactions increases. An exception is the possibility of using in combination with any other NSAID to enhance the analgesic effect.

In some patients, two NSAIDs may be administered at different times of the day, for example, a fast-absorbing NSAID in the morning and afternoon, and a long-acting NSAID in the evening.

DRUG INTERACTIONS

Quite often, patients who receive NSAIDs are prescribed other drugs. In this case, it is necessary to take into account the possibility of their interaction with each other. So, NSAIDs may enhance the effect of indirect anticoagulants and oral hypoglycemic agents.. In the same time, they weaken the effect of antihypertensive drugs, increase the toxicity of aminoglycoside antibiotics, digoxin and some other drugs, which is of significant clinical importance and entails a number of practical recommendations (). If possible, the simultaneous administration of NSAIDs and diuretics should be avoided, due, on the one hand, to the weakening of the diuretic effect and, on the other, the risk of developing renal failure. The most dangerous is the combination with triamterene.

Many drugs prescribed simultaneously with NSAIDs, in turn, can affect their pharmacokinetics and pharmacodynamics:
– aluminum-containing antacids(almagel, maalox and others) and cholestyramine reduces the absorption of NSAIDs in the gastrointestinal tract. Therefore, the concomitant administration of such antacids may require an increase in the dose of NSAIDs, and intervals of at least 4 hours are necessary between taking cholestyramine and NSAIDs;
– sodium bicarbonate enhances the absorption of NSAIDs in the gastrointestinal tract;
– the anti-inflammatory effect of NSAIDs is enhanced by glucocorticoids and "slow-acting" (basic) anti-inflammatory drugs(preparations of gold, aminoquinolines);
– the analgesic effect of NSAIDs is enhanced by narcotic analgesics and sedatives.

OTC NSAID USE

For over-the-counter use for many years in world practice, , , , and their combinations are widely used. In recent years, , , and are allowed for over-the-counter use.

Table 5 Influence of NSAIDs on the effect of other drugs.
By Brooks P.M., Day R.O. 1991 () with additions

A drug NSAIDs Action Recommendations Pharmacokinetic interaction Indirect anticoagulants Oxyphenbutazone Inhibition of metabolism in the liver, increased anticoagulant effect Avoid these NSAIDs if possible, or maintain strict control Everything, especially Displacement from the connection with plasma proteins, increased anticoagulant effect Avoid NSAIDs if possible or maintain strict control Oral hypoglycemic drugs (sulfonylurea derivatives) Oxyphenbutazone Inhibition of metabolism in the liver, increased hypoglycemic effect Avoid NSAIDs if possible or strictly control blood glucose levels Everything, especially Displacement by plasma proteins, increased hypoglycemic effect Digoxin All Inhibition of renal excretion of digoxin in case of impaired renal function (especially in young children and the elderly), an increase in its concentration in the blood, an increase in toxicity. Less likely to interact with normal kidney function Avoid NSAIDs if possible or strictly control creatinine clearance and blood digoxin levels Antibiotics - aminoglycosides All Inhibition of renal excretion of aminoglycosides, increasing their concentration in the blood Strict control of the concentration of aminoglycosides in the blood Methotrexate (high "non-rheumatic" doses) All Inhibition of renal excretion of methotrexate, an increase in its concentration in the blood and toxicity (interaction with a "rheumatological" dose of methotrexate is not observed) Simultaneous administration is contraindicated. Can NSAIDs be used during chemotherapy intervals? Lithium preparations All (to a lesser extent - , ) Inhibition of renal excretion of lithium, increase in its concentration in the blood and toxicity Use aspirin or sulindac if an NSAID is needed. Strict control of the concentration of lithium in the blood Phenytoin Oxyphenbutazone Inhibition of metabolism, increased blood concentrations and toxicity Avoid these NSAIDs if possible or strictly control blood levels of phenytoin Pharmacodynamic interaction Antihypertensive drugs Beta blockers Diuretics ACE inhibitors* Weakening hypotensive action due to inhibition of PG synthesis in the kidneys (sodium and water retention) and blood vessels (vasoconstriction) Use sulindac and, if possible, avoid other NSAIDs for hypertension. Strict control of blood pressure. Increased antihypertensive therapy may be required Diuretics To the greatest extent - , . In the least - Weakening of diuretic and natriuretic action, deterioration in heart failure Avoid NSAIDs (except sulindac) in heart failure, strictly monitor the patient's condition Indirect anticoagulants All Increased risk of gastrointestinal bleeding due to mucosal damage and inhibition of platelet aggregation Avoid NSAIDs if possible High risk combinations Diuretics All All (to a lesser extent - ) Increased risk of kidney failure The combination is contraindicated Triamterene High risk of developing acute renal failure The combination is contraindicated All potassium-sparing All High risk of developing hyperkalemia Avoid such combinations or strictly control plasma potassium levels

Indications: to provide analgesic and antipyretic action for colds, headache and toothache, muscle and joint pain, back pain, dysmenorrhea.

It is necessary to warn patients that NSAIDs have only a symptomatic effect and do not have either antibacterial or antiviral activity. Therefore, if fever, pain, deterioration of the general condition persist, they should consult a doctor.

CHARACTERISTICS OF INDIVIDUAL PREPARATIONS

NSAIDs WITH PROVEN ANTI-INFLAMMATORY ACTIVITY

NSAIDs belonging to this group have a clinically significant anti-inflammatory effect, therefore, they find wide application primarily as anti-inflammatory agents, including rheumatological diseases in adults and children. Many of the drugs are also used as analgesics and antipyretics.

ACETYLSALICYLIC ACID
(Aspirin, Aspro, Kolfarit)

Acetylsalicylic acid is the oldest NSAID. In clinical trials, it usually serves as the standard against which other NSAIDs are compared for efficacy and tolerability.

Aspirin is tradename acetylsalicylic acid proposed by Bayer (Germany). Over time, it has become so identified with this drug that it is now used as a generic drug in most countries of the world.

Pharmacodynamics

The pharmacodynamics of aspirin depends on daily dose:

small doses - 30-325 mg - cause inhibition of platelet aggregation;
average doses - 1.5-2 g - have an analgesic and antipyretic effect;
large doses - 4-6 g - have an anti-inflammatory effect.

At a dose of more than 4 g, aspirin increases excretion uric acid(uricosuric effect), when prescribed in smaller doses, its excretion is delayed.

Pharmacokinetics

Well absorbed in the gastrointestinal tract. Absorption of aspirin is enhanced by crushing the tablet and taking it with warm water, as well as when using "effervescent" tablets, which are dissolved in water before taking. The half-life of aspirin is only 15 minutes. Under the action of esterases of the gastric mucosa, liver and blood, salicylate is cleaved from aspirin, which has the main pharmacological activity. The maximum concentration of salicylate in the blood develops 2 hours after taking aspirin, its half-life is 4-6 hours. It is metabolized in the liver, excreted in the urine, and with an increase in the pH of the urine (for example, in the case of the appointment of antacids), excretion increases. When using large doses of aspirin, it is possible to saturate metabolizing enzymes and increase the half-life of salicylate up to 15-30 hours.

Interactions

Glucocorticoids accelerate the metabolism and excretion of aspirin.

The absorption of aspirin in the gastrointestinal tract is enhanced by caffeine and metoclopramide.

Aspirin inhibits gastric alcohol dehydrogenase, which leads to an increase in the level of ethanol in the body, even with its moderate (0.15 g / kg) use ().

Adverse reactions

Gastrotoxicity. Even when used in low doses - 75-300 mg / day (as an antiplatelet agent) - aspirin can cause damage to the gastric mucosa and lead to the development of erosions and / or ulcers, which are often complicated by bleeding. The risk of bleeding is dose-dependent: when administered at a dose of 75 mg / day, it is 40% lower than at a dose of 300 mg, and 30% lower than at a dose of 150 mg (). Even slightly, but constantly bleeding erosions and ulcers can lead to a systematic loss of blood in the feces (2-5 ml / day) and the development of iron deficiency anemia.

Somewhat less gastrotoxicity have dosage forms with enteric-soluble coating. Some patients taking aspirin may develop adaptation to its gastrotoxic effects. It is based on a local increase in mitotic activity, a decrease in neutrophil infiltration and an improvement in blood flow ().

Increased bleeding due to a violation of platelet aggregation and inhibition of prothrombin synthesis in the liver (the latter - at a dose of aspirin more than 5 g / day), so the use of aspirin in combination with anticoagulants is dangerous.

Hypersensitivity reactions: skin rashes, bronchospasm. A special nosological form stands out - the Fernand-Vidal syndrome ("aspirin triad"): a combination of nasal polyposis and / or paranasal sinuses, bronchial asthma and complete intolerance to aspirin. Therefore, aspirin and other NSAIDs are recommended to be used with great caution in patients with bronchial asthma.

Reye's syndrome- develops when aspirin is prescribed to children with viral infections(influenza, chicken pox). It presents with severe encephalopathy, cerebral edema, and liver damage that occurs without jaundice, but with high levels of cholesterol and liver enzymes. Gives very high lethality (up to 80%). Therefore, aspirin should not be used for acute respiratory viral infections in children of the first 12 years of life.

Overdose or poisoning in mild cases, it manifests itself with symptoms of "salicylicism": tinnitus (a sign of "saturation" with salicylate), stupor, hearing loss, headache, visual disturbances, sometimes nausea and vomiting. In severe intoxication, disorders of the central nervous system and water-electrolyte metabolism develop. There is shortness of breath (as a result of stimulation respiratory center), disorders of the acid-base state (first respiratory alkalosis due to loss of carbon dioxide, then metabolic acidosis due to inhibition of tissue metabolism), polyuria, hyperthermia, dehydration. Myocardial oxygen consumption increases, heart failure, pulmonary edema may develop. The most sensitive to the toxic effect of salicylate are children under 5 years of age, in whom, as in adults, it is manifested by severe disorders of the acid-base state and neurological symptoms. The severity of intoxication depends on the dose of aspirin taken ().

Mild to moderate intoxication occurs at 150–300 mg/kg, 300–500 mg/kg leads to severe poisoning, and doses greater than 500 mg/kg are potentially lethal. Relief measures shown in .

Table 6 Symptoms of acute aspirin poisoning in children. (Applied Therapeutics, 1996)

Table 7 Measures to help with aspirin intoxication.

• Gastric lavage
• Introduction activated carbon– up to 15 g
• Plentiful drink (milk, juice) - up to 50-100 ml / kg / day
• Intravenous administration of polyionic hypotonic solutions (1 part 0.9% sodium chloride and 2 parts 10% glucose)
• With collapse - intravenous administration of colloidal solutions
• With acidosis - intravenous administration of sodium bicarbonate. It is not recommended to enter before determining the pH of the blood, especially in children with anuria
• Intravenous administration of potassium chloride
• Physical cooling with water, not alcohol!
• Hemosorption
• Exchange transfusion
• For kidney failure, hemodialysis

Indications

Aspirin is one of the drugs of choice for the treatment of rheumatoid arthritis, including juvenile arthritis. According to the recommendations of most recent rheumatology guidelines, anti-inflammatory therapy for rheumatoid arthritis should begin with aspirin. At the same time, however, it must be borne in mind that its anti-inflammatory effect is manifested when taking high doses, which may be poorly tolerated by many patients.

Aspirin is often used as an analgesic and antipyretic. Controlled clinical studies have shown that aspirin can be effective for many types of pain, including malignant tumors (). Comparative characteristics analgesic effect of aspirin and other NSAIDs is presented in

Despite the fact that most NSAIDs in vitro have the ability to inhibit platelet aggregation, aspirin is the most widely used in the clinic as an antiplatelet agent, since controlled clinical trials have proven its effectiveness in angina pectoris, myocardial infarction, transient cerebrovascular accident and some other diseases. Aspirin is prescribed immediately for suspected myocardial infarction or ischemic stroke. At the same time, aspirin has little effect on venous thrombosis, so it should not be used to prevent postoperative thrombosis in surgery where heparin is the drug of choice.

It has been established that with long-term systematic (long-term) intake in low doses (325 mg/day), aspirin reduces the incidence of colorectal cancer. First of all, aspirin prophylaxis is indicated for people at risk for colorectal cancer: family history (colorectal cancer, adenoma, adenomatous polyposis); inflammatory diseases of the large intestine; breast, ovarian, endometrial cancer; cancer or adenoma of the large intestine ().

Table 8 Comparative characteristics of the analgesic action of aspirin and other NSAIDs.
Drugs of Choice from the Medical Letter, 1995

A drug single dose Interval Maximum daily dose Note inside 500-1000 mg 4-6 hours 4000 mg Duration of action after a single dose of 4 hours inside 500-1000 mg 4-6 hours 4000 mg The effectiveness is equal to aspirin; 1000 mg is usually more effective than 650 mg; duration of action 4 hours. Inside the 1st dose of 1000 mg, then 500 mg 8-12 hours 1500 mg 500 mg diflunisal > 650 mg aspirin or paracetamol, approximately equal to paracetamol/codeine; acts slowly but for a long time inside 50 mg 8 ocloc'k 150 mg Comparable to aspirin, longer acting inside 200-400 mg 6-8 hours 1200 mg 200 mg is approximately equal to 650 mg of aspirin, 400 mg > 650 mg aspirin inside 200 mg 4-6 hours 1200 mg Comparable to aspirin inside 50-100 mg 6-8 hours 300 mg 50 mg > 650 mg aspirin; 100 mg > inside 200-400 mg 4-8 hours 2400 mg 200 mg = 650 mg of aspirin or paracetamol; 400 mg = paracetamol/codeine combinations inside 25-75 mg 4-8 hours 300 mg 25 mg = 400 mg ibuprofen and > 650 mg aspirin; 50 mg > paracetamol/codeine combinations Intramuscular 30-60 mg 6 hours 120 mg Comparable to 12 mg morphine, longer acting, no longer than 5 days Inside the 1st dose of 500 mg, then 250 mg 6 hours 1250 mg Comparable to aspirin, but more effective for dysmenorrhea, no longer than 7 days inside 1st dose 500 mg, then 250 mg 6-12 hours 1250 mg 250 mg is approximately equal to 650 mg of aspirin, slower but longer acting; 500 mg > 650 mg aspirin, same rapid effect as aspirin inside 1st dose 550 mg, then 275 mg 6-12 hours 1375 mg 275 mg is approximately equal to 650 mg of aspirin, slower but longer acting; 550 mg > 650 mg aspirin, same rapid effect as aspirin

Dosage

Adults: non-rheumatic diseases - 0.5 g 3-4 times a day; rheumatic diseases - the initial dose is 0.5 g 4 times a day, then it is increased by 0.25-0.5 g per day every week;
as an antiplatelet agent - 100-325 mg / day in one dose.

Children: non-rheumatic diseases - under the age of 1 year - 10 mg / kg 4 times a day, older than a year - 10-15 mg / kg 4 times a day;
rheumatic diseases - with a body weight of up to 25 kg - 80-100 mg / kg / day, with a weight of more than 25 kg - 60-80 mg / kg / day.

Release forms:

- tablets of 100, 250, 300 and 500 mg;
- "effervescent tablets" ASPRO-500. Included in combined preparations alkaseltzer, aspirin C, aspro-C forte, citramon P and others.

LYSINE MONOACETYLSALICYLATE
(Aspisol, Laspal)

Adverse reactions

Widespread use of phenylbutazone is limited by its frequent and serious adverse reactions, which occur in 45% of patients. The most dangerous depressive effect of the drug on the bone marrow, which results in hematotoxic reactions- aplastic anemia and agranulocytosis, often causing death. The risk of aplastic anemia is higher in women, in people over 40, with long-term use. However, even with a short-term intake by young people, fatal aplastic anemia can develop. Leukopenia, thrombocytopenia, pancytopenia and hemolytic anemia are also noted.

In addition, adverse reactions from the gastrointestinal tract (erosive and ulcerative lesions, bleeding, diarrhea), fluid retention in the body with the appearance of edema, skin rashes, ulcerative stomatitis, enlarged salivary glands, disorders of the central nervous system (lethargy, agitation, tremor), hematuria, proteinuria, liver damage.

Phenylbutazone has cardiotoxicity (exacerbation is possible in patients with heart failure) and can cause an acute pulmonary syndrome, manifested by shortness of breath and fever. A number of patients experience hypersensitivity reactions in the form of bronchospasm, generalized lymphadenopathy, skin rashes, Lyell and Stevens-Johnson syndromes. Phenylbutazone and especially its metabolite oxyphenbutazone can exacerbate porphyria.

Indications

Phenylbutazone should be used as reserve NSAIDs with the ineffectiveness of other drugs, a short course. The greatest effect is observed in Bechterew's disease, gout.

Warnings

Do not use phenylbutazone and combined preparations containing it ( rheopyrite, pyrabutol) as analgesics or antipyretics in wide clinical practice.

Given the possibility of developing life-threatening hematological complications, it is necessary to warn patients about their early manifestations and strictly follow the rules for prescribing pyrazolones and pyrazolidines ().

Table 9 Rules for the use of phenylbutazone and other derivatives of pyrazolidine and pyrazolone

1. Assign only after careful collection of anamnesis, clinical and laboratory examination with the determination of erythrocytes, leukocytes and platelets. These studies should be repeated at the slightest suspicion of hematotoxicity.
2. Patients should be warned about the immediate discontinuation of treatment and urgent medical attention if the following symptoms appear:
   • fever, chills, sore throat, stomatitis (symptoms of agranulocytosis);
   • dyspepsia, epigastric pain, unusual bleeding and bruising, tarry stools (symptoms of anemia);
   • skin rash, itching;
   • significant weight gain, edema.
3. To evaluate the effectiveness of a weekly course is enough. If there is no effect, the drug should be discontinued. In patients older than 60 years, phenylbutazone should not be used for more than 1 week.

Phenylbutazone is contraindicated in patients with hematopoietic disorders, erosive and ulcerative lesions of the gastrointestinal tract (including their history), cardiovascular diseases, thyroid pathology, impaired liver and kidney function, and allergies to aspirin and other NSAIDs. It may worsen the condition of patients with systemic lupus erythematosus.

Dosage

Adults: initial dose - 450-600 mg / day in 3-4 doses. After achieving a therapeutic effect, maintenance doses are used - 150-300 mg / day in 1-2 doses.
In children under 14 years of age does not apply.

Release forms:

- tablets of 150 mg;
- ointment, 5%.

CLOFESON ( Percluson)

An equimolar compound of phenylbutazone and clofexamide. Clofexamide has a predominantly analgesic and less anti-inflammatory effect, complementing the effect of phenylbutazone. Tolerability of clofezon is somewhat better than. Adverse reactions develop less frequently, but precautions must be observed ().

Indications for use

Indications for use are the same as

Dosage

Adults: 200-400 mg 2-3 times a day orally or rectally.
Children over 20 kg body weight: 10-15 mg/kg/day.

Release forms:

- capsules of 200 mg;
- suppositories of 400 mg;
- ointment (1 g contains 50 mg of clofeson and 30 mg of clofexamide).

INDOMETACIN
(Indocid, Indobene, Metindol, Elmetatsin)

Indomethacin is one of the most powerful NSAIDs.

Pharmacokinetics

The maximum concentration in the blood develops 1-2 hours after oral administration of conventional and 2-4 hours after administration of prolonged ("retard") dosage forms. Eating slows down absorption. With rectal administration, it is absorbed somewhat worse and the maximum concentration in the blood develops more slowly. The half-life is 4-5 hours.

Interactions

Indomethacin, more than other NSAIDs, impairs renal blood flow, therefore, it can significantly weaken the effect of diuretics and antihypertensive drugs. The combination of indomethacin with the potassium-sparing diuretic triamterene is very dangerous., as it provokes the development of acute renal failure.

Adverse reactions

The main disadvantage of indomethacin is the frequent development of adverse reactions (in 35-50% of patients), and their frequency and severity depend on the daily dose. In 20% of cases, due to adverse reactions, the drug is canceled.

The most characteristic neurotoxic reactions: headache (caused by cerebral edema), dizziness, stupor, inhibition of reflex activity; gastrotoxicity(higher than aspirin); nephrotoxicity(should not be used in renal and heart failure); hypersensitivity reactions(possible cross-allergy with).

Indications

Indomethacin is especially effective in ankylosing spondylitis and acute gout attacks. Widely used in rheumatoid arthritis and active rheumatism. In juvenile rheumatoid arthritis, it is a reserve drug. There is extensive experience in the use of indomethacin in osteoarthritis of the hip and knee joints. However, it has recently been shown that in patients with osteoarthritis, it accelerates the destruction of articular cartilage. A special area of ​​​​use of indomethacin is neonatology (see below).

Warnings

Due to the powerful anti-inflammatory effect, indomethacin can mask the clinical symptoms of infections, so it is not recommended for patients with infections.

Dosage

Adults: initial dose - 25 mg 3 times a day, maximum - 150 mg / day. The dose is increased gradually. Retard tablets and rectal suppositories appoint 1-2 times a day. Sometimes they are used only at night, and another NSAID is prescribed in the morning and afternoon. Ointment is applied externally.
Children: 2-3 mg/kg/day in 3 divided doses.

Release forms:

- enteric-coated tablets 25 mg; - tablets "retard" 75 mg; - suppositories of 100 mg; - ointment, 5 and 10%.

The use of indomethacin in neonatology

Indomethacin is used in preterm infants to pharmacologically close the patent ductus arteriosus. Moreover, in 75-80% of the drug allows you to achieve complete closure of the arterial duct and avoid surgery. The effect of indomethacin is due to the inhibition of the synthesis of PG-E 1, which keeps the ductus arteriosus open. The best results are observed in children with III-IV degree of prematurity.

Indications for the appointment of indomethacin to close the arterial duct:

1. Birth weight before 1750
2. Severe hemodynamic disturbances - shortness of breath, tachycardia, cardiomegaly.
3. Ineffectiveness of traditional therapy carried out within 48 hours (fluid restriction, diuretics, cardiac glycosides).

Contraindications: infections, birth trauma, coagulopathy, kidney pathology, necrotizing enterocolitis.

Undesirable reactions: mainly from the side of the kidneys - deterioration in blood flow, increased creatinine and blood urea, decreased glomerular filtration, diuresis.

Dosage

Inside 0.2-0.3 mg / kg 2-3 times every 12-24 hours. If there is no effect, further use of indomethacin is contraindicated.

SULINDAK ( Clinoril)

Pharmacokinetics

It is a "prodrug", in the liver it turns into an active metabolite. The maximum concentration of the active metabolite of sulindac in the blood is observed 3-4 hours after ingestion. The half-life of sulindac is 7-8 hours, and the active metabolite is 16-18 hours, which provides a long-lasting effect and the possibility of taking 1-2 times a day.

Adverse reactions

Dosage

Adults: inside, rectally and intramuscularly - 20 mg / day in one dose (introduction).
Children: doses have not been established.

Release forms:

- tablets of 20 mg;
- capsules of 20 mg;
- suppositories of 20 mg.

LORNOXICAM ( Xefocam)

NSAIDs from the group of oxycams - chlortenoxicam. In terms of inhibition of COX, it surpasses other oxicams, and blocks COX-1 and COX-2 to approximately the same extent, occupying an intermediate position in the classification of NSAIDs, built on the principle of selectivity. It has a pronounced analgesic and anti-inflammatory effect.

The analgesic effect of lornoxicam consists of a violation of the generation of pain impulses and a decrease in pain perception (especially in chronic pain). When administered intravenously, the drug is able to increase the level of endogenous opioids, thereby activating the physiological antinociceptive system of the body.

Pharmacokinetics

Well absorbed in the gastrointestinal tract, food slightly reduces bioavailability. Maximum plasma concentrations are observed after 1-2 hours. With intramuscular administration, the maximum plasma level is observed after 15 minutes. It penetrates well into the synovial fluid, where its concentrations reach 50% of plasma levels, and remains in it for a long time (up to 10-12 hours). Metabolized in the liver, excreted through the intestines (mainly) and kidneys. The half-life is 3-5 hours.

Adverse reactions

Lornoxicam is less gastrotoxic than first-generation oxicams (piroxicam, tenoxicam). This is partly due to the short half-life, which creates opportunities to restore the protective level of PG in the gastrointestinal mucosa. In controlled studies, it was found that lornoxicam is superior in tolerability to indomethacin and is practically not inferior to diclofenac.

Indications

– Pain syndrome (acute and chronic pain, including cancer).
When administered intravenously, lornoxicam at a dose of 8 mg is not inferior in terms of the severity of the analgesic effect to meperidine (similar to domestic promedol). When taken orally in patients with postoperative pain, lornoxicam 8 mg is approximately equivalent to ketorolac 10 mg, ibuprofen 400 mg, and aspirin 650 mg. In severe pain syndrome, lornoxicam can be used in combination with opioid analgesics, which allows to reduce the dose of the latter.
– Rheumatic diseases (rheumatoid arthritis, psoriatic arthritis, osteoarthritis).

Dosage

Adults:
with pain syndrome - inside - 8 mg x 2 times a day; it is possible to take a loading dose of 16 mg; i / m or / in - 8-16 mg (1-2 doses with an interval of 8-12 hours); in rheumatology - inside 4-8 mg x 2 times a day.
Doses for kids under 18s not established.

Release forms:

- tablets of 4 and 8 mg;
- vials of 8 mg (for the preparation of an injection solution).

MELOXICAM ( Movalis)

It is a representative of a new generation of NSAIDs - selective COX-2 inhibitors. Due to this property, meloxicam selectively inhibits the formation of prostaglandins involved in the formation of inflammation. At the same time, it inhibits COX-1 much weaker, therefore, it has less effect on the synthesis of prostaglandins that regulate renal blood flow, the production of protective mucus in the stomach, and platelet aggregation.

Controlled studies in patients with rheumatoid arthritis have shown that in terms of anti-inflammatory activity, it is not inferior to meloxicam, and, but significantly less causes unwanted reactions from the gastrointestinal tract and kidneys ().

Pharmacokinetics

Bioavailability when taken orally is 89% and does not depend on food intake. The maximum concentration in the blood develops after 5-6 hours. Equilibrium concentration is created in 3-5 days. The half-life is 20 hours, which allows you to prescribe the drug 1 time per day.

Indications

Rheumatoid arthritis, osteoarthritis.

Dosage

Adults: inside and intramuscularly at 7.5-15 mg 1 time per day.
In children the efficacy and safety of the drug has not been studied.

Release forms:

- tablets of 7.5 and 15 mg;
- 15 mg ampoules.

NABUMETHONE ( Relafen)

Dosage

Adults: 400-600 mg 3-4 times a day, preparations "retard" - 600-1200 mg 2 times a day.
Children: 20-40 mg/kg/day in 2-3 divided doses.
Since 1995, in the United States, ibuprofen has been approved for over-the-counter use in children over 2 years of age with fever and pain at 7.5 mg/kg up to 4 times a day, with a maximum of 30 mg/kg/day.

Release forms:

- tablets of 200, 400 and 600 mg;
- tablets "retard" 600, 800 and 1200 mg;
- cream, 5%.

NAPROXEN ( Naprosin)

One of the most commonly used NSAIDs. It is superior in anti-inflammatory activity. The anti-inflammatory effect develops slowly, with a maximum after 2-4 weeks. It has a strong analgesic and antipyretic effect. The antiaggregatory effect is manifested only when high doses of the drug are prescribed. Does not have uricosuric activity.

Pharmacokinetics

It is well absorbed after oral administration and rectal administration. The maximum concentration in the blood is observed 2-4 hours after ingestion. The half-life is about 15 hours, which allows you to assign it 1-2 times a day.

Adverse reactions

Gastrotoxicity is less than that of, and. Nephrotoxicity is observed, as a rule, only in patients with renal pathology and heart failure. Allergic reactions are possible, cases of cross-allergy with.

Indications

It is widely used for rheumatism, ankylosing spondylitis, rheumatoid arthritis in adults and children. In patients with osteoarthritis, it inhibits the activity of the proteoglycanase enzyme, preventing degenerative changes in the articular cartilage, which compares favorably with. It is widely used as an analgesic, including for postoperative and postpartum pain, and gynecological procedures. High efficiency was noted for dysmenorrhea, paraneoplastic fever.

Dosage

Adults: 500-1000 mg/day in 1-2 doses orally or rectally. The daily dose may be increased to 1500 mg for a limited period (up to 2 weeks). In acute pain syndrome (bursitis, tendovaginitis, dysmenorrhea), the 1st dose is 500 mg, then 250 mg every 6-8 hours.
Children: 10-20 mg/kg/day in 2 divided doses. As an antipyretic - 15 mg / kg per dose.

Release forms:

- tablets of 250 and 500 mg;
- suppositories of 250 and 500 mg;
- suspension containing 250 mg / 5 ml;
– gel, 10%.

NAPROXEN-SODIUM ( Aliv, Apranax)

Indications

Used as analgesic and antipyretic. For a quick effect, it is administered parenterally.

Dosage

Adults: inside 0.5-1 g 3-4 times a day, intramuscularly or intravenously, 2-5 ml of 50% solution 2-4 times a day.
Children: 5-10 mg/kg 3-4 times a day. With hyperthermia intravenously or intramuscularly in the form of 50% solution: up to 1 year - 0.01 ml / kg, older than 1 year - 0.1 ml / year of life per injection.

Release forms:

- tablets of 100 and 500 mg;
- 1 ml ampoules of 25% solution, 1 and 2 ml of 50% solution;
- drops, syrup, candles.

AMINOPHENAZONE ( Amidopyrine)

It has been used for many years as an analgesic and antipyretic. More toxic than . More often causes severe skin allergic reactions, especially when combined with sulfonamides. Currently, aminophenazone banned and discontinued, since when interacting with food nitrites, it can lead to the formation of carcinogenic compounds.

Despite this, the pharmacy network continues to receive drugs containing aminophenazone ( omazol, anapirin, pentalgin, pirabutol, piranal, pircofen, reopyrin, theofedrin N).

PROPIPHENAZONE

It has a pronounced analgesic and antipyretic effect. Rapidly absorbed in the gastrointestinal tract, the maximum concentration in the blood develops 30 minutes after ingestion.

Compared to other pyrazolone derivatives, it is the safest. With its use, the development of agranulocytosis was not noted. In rare cases, there is a decrease in the number of platelets and leukocytes.

It is not used as a monopreparation, it is part of combined preparations saridon and plivalgin.

PHENACETHIN

Pharmacokinetics

Well absorbed in the gastrointestinal tract. Metabolized in the liver, partially turning into an active metabolite. Other metabolites of phenacetin are toxic. The half-life is 2-3 hours.

Adverse reactions

Phenacetin is highly nephrotoxic. It can cause tubulointerstitial nephritis due to ischemic changes in the kidneys, which are manifested by back pain, dysuric phenomena, hematuria, proteinuria, cylindruria ("analgesic nephropathy", "phenacetin kidney"). The development of severe renal failure has been described. Nephrotoxic effects are more pronounced with prolonged use in combination with other analgesics, more often observed in women.

Metabolites of phenacetin can cause the formation of methemoglobin and hemolysis. The drug also has carcinogenic properties: it can lead to the development of bladder cancer.

Phenacetin is banned in many countries.

Dosage

Adults: 250-500 mg 2-3 times a day.
In children does not apply.

Release forms:

Included in various combined preparations: tablets pircofen, sedalgin, theofedrin N, candles cefekon.

PARACETAMOL
(Kalpol, Lekadol, Meksalen, Panadol, Efferalgan)

Paracetamol (generic name in some countries) acetaminophen) is an active metabolite. Compared to phenacetin, it is less toxic.

More inhibits the synthesis of prostaglandins in the central nervous system than in peripheral tissues. Therefore, it has a predominantly "central" analgesic and antipyretic effect and has a very weak "peripheral" anti-inflammatory activity. The latter can manifest itself only with a low content of peroxide compounds in the tissues, for example, with osteoarthritis, with acute injury soft tissues, but not in rheumatic diseases.

Pharmacokinetics

Paracetamol is well absorbed when administered orally and rectally. The maximum concentration in the blood develops 0.5-2 hours after ingestion. In vegetarians, the absorption of paracetamol in the gastrointestinal tract is significantly weakened. The drug is metabolized in the liver in 2 stages: first, under the action of cytochrome P-450 enzyme systems, intermediate hepatotoxic metabolites are formed, which are then cleaved with the participation of glutathione. Less than 5% of the administered paracetamol is excreted unchanged by the kidneys. The half-life is 2-2.5 hours. The duration of action is 3-4 hours.

Adverse reactions

Paracetamol is considered one of the safest NSAIDs. So, unlike, it does not cause Reye's syndrome, does not have gastrotoxicity, and does not affect platelet aggregation. Unlike and does not cause agranulocytosis and aplastic anemia. Allergic reactions to paracetamol are rare.

Recently, data have been obtained that with prolonged use of paracetamol more than 1 tablet per day (1000 or more tablets per life), the risk of developing severe analgesic nephropathy, leading to terminal renal failure, doubles (). It is based on the nephrotoxic effect of paracetamol metabolites, especially para-aminophenol, which accumulates in the renal papillae, binds to SH-groups, causing severe violations of the function and structure of cells, up to their death. At the same time, the systematic use of aspirin is not associated with such a risk. Thus, paracetamol is more nephrotoxic than aspirin and should not be considered a "perfectly safe" drug.

You should also remember about hepatotoxicity paracetamol when taken in very large (!) doses. Its simultaneous administration at a dose of more than 10 g in adults or more than 140 mg / kg in children leads to poisoning, accompanied by severe liver damage. The reason is the depletion of glutathione reserves and the accumulation of intermediate products of the metabolism of paracetamol, which have a hepatotoxic effect. Symptoms of poisoning are divided into 4 stages ().

Table 10 Symptoms of paracetamol intoxication. (According to Merck Manual, 1992)

Stage Term Clinic I First 12-24 hours Mild symptoms of gastrointestinal irritation. The patient does not feel sick. II 2-3 days Gastrointestinal symptoms, especially nausea and vomiting; increase in AST, ALT, bilirubin, prothrombin time. III 3-5 days indomitable vomiting; high values ​​of AST, ALT, bilirubin, prothrombin time; signs of liver failure. IV Later 5 days Recovery of liver function or death from liver failure.

A similar picture can be observed when taking normal doses of the drug in the case of concomitant use of inducers of cytochrome P-450 enzymes, as well as in alcoholics (see below).

Relief measures with paracetamol intoxication are presented in. It must be borne in mind that forced diuresis in paracetamol poisoning is ineffective and even dangerous, peritoneal dialysis and hemodialysis are ineffective. In no case should you use antihistamines, glucocorticoids, phenobarbital and ethacrynic acid, which can have an inducing effect on cytochrome P-450 enzyme systems and enhance the formation of hepatotoxic metabolites.

Interactions

The absorption of paracetamol in the gastrointestinal tract is enhanced by metoclopramide and caffeine.

Liver enzyme inducers (barbiturates, rifampicin, difenin and others) accelerate the breakdown of paracetamol to hepatotoxic metabolites and increase the risk of liver damage.

Table 11 Measures to help with intoxication with paracetamol

• Gastric lavage.
• Activated charcoal inside.
• Inducing vomiting.
• Acetylcysteine ​​(is a donator of glutathione) - 20% solution inside.
• Glucose intravenously.
• Vitamin K 1 (phytomenadione) - 1-10 mg intramuscularly, native plasma, coagulation factors (with a 3-fold increase in prothrombin time).

Similar effects can be observed in individuals who systematically consume alcohol. They have hepatotoxicity of paracetamol even when used in therapeutic doses (2.5-4 g / day), especially if it is taken after a short period of time after alcohol ().

Indications

Paracetamol is currently considered as effective analgesic and antipyretic for a wide range of applications. It is primarily recommended in the presence of contraindications to other NSAIDs: in patients with bronchial asthma, in persons with a history of ulcers, in children with viral infections. In terms of analgesic and antipyretic activity, paracetamol is close to.

Warnings

Paracetamol should be used with caution in patients with impaired liver and kidney function, as well as in those taking drugs that affect liver function.

Dosage

Adults: 500-1000 mg 4-6 times a day.
Children: 10-15 mg/kg 4-6 times a day.

Release forms:

- tablets of 200 and 500 mg;
- syrup 120 mg / 5 ml and 200 mg / 5 ml;
- suppositories of 125, 250, 500 and 1000 mg;
- "effervescent" tablets of 330 and 500 mg. Included in combined preparations soridon, solpadein, tomapirin, citramon P and others.

KETOROLAC ( Toradol, Ketrodol)

The main clinical value of the drug is its powerful analgesic effect, in terms of which it surpasses many other NSAIDs.

It has been established that 30 mg of ketorolac administered intramuscularly is approximately equivalent to 12 mg of morphine. At the same time, adverse reactions characteristic of morphine and other narcotic analgesics (nausea, vomiting, respiratory depression, constipation, urinary retention) are much less common. The use of ketorolac does not lead to the development of drug dependence.

Ketorolac also has antipyretic and antiaggregatory effects.

Pharmacokinetics

Almost completely and rapidly absorbed in the gastrointestinal tract, oral bioavailability is 80-100%. The maximum concentration in the blood develops 35 minutes after ingestion and 50 minutes after intramuscular injection. Excreted by the kidneys. The half-life is 5-6 hours.

Adverse reactions

The most frequently noted gastrotoxicity and increased bleeding due to antiaggregatory action.

Interaction

When combined with opioid analgesics, the analgesic effect is enhanced, which makes it possible to use them at lower doses.

Intravenous or intraarticular administration of ketorolac in combination with local anesthetics(lidocaine, bupivacaine) provides better pain relief than the use of only one of the drugs after arthroscopy and operations on the upper extremities.

Indications

It is used to relieve pain syndrome of various localization: renal colic, pain in trauma, in neurological diseases, in cancer patients (especially with bone metastases), in the postoperative and postpartum period.

There is evidence of the possibility of using ketorolac before surgery in combination with morphine or fentanyl. This allows you to reduce the dose of opioid analgesics by 25-50% in the first 1-2 days of the postoperative period, which is accompanied by a faster recovery of the function of the gastrointestinal tract, less nausea and vomiting, and reduces the length of stay of patients in the hospital ().

It is also used for pain relief in operative dentistry and orthopedic treatment procedures.

Warnings

Ketorolac should not be used before long-term operations with a high risk of bleeding, as well as for maintenance anesthesia during operations, for pain relief in childbirth, and relief of pain in myocardial infarction.

The course of application of Ketorolac should not exceed 7 days, and in persons over 65 years of age, the drug should be administered with caution.

Dosage

Adults: orally 10 mg every 4 to 6 hours; the highest daily dose is 40 mg; duration of application is not more than 7 days. Intramuscularly and intravenously - 10-30 mg; the highest daily dose is 90 mg; duration of application is not more than 2 days.
Children: intravenously 1st dose - 0.5-1 mg / kg, then 0.25-0.5 mg / kg every 6 hours.

Release forms:

- tablets of 10 mg;
- 1 ml ampoules.

COMBINED DRUGS

There are a number of combined preparations containing, in addition to NSAIDs, other drugs that, due to their specific properties, can enhance the analgesic effect of NSAIDs, increase their bioavailability and reduce the risk of adverse reactions.

SARIDON

Consists of, and caffeine. The ratio of analgesics in the preparation is 5:3, in which they act as synergists, since paracetamol in this case increases the bioavailability of propyphenazone by one and a half times. Caffeine normalizes the tone of the cerebral vessels, accelerates blood flow, without stimulating the central nervous system in the dose used, so it enhances the effect of analgesics for headaches. In addition, it improves the absorption of paracetamol. Saridon, in general, is characterized by high bioavailability and rapid development of the analgesic effect.

Indications

Pain syndrome of various localization (headache, toothache, pain in rheumatic diseases, dysmenorrhea, fever).

Dosage

1-2 tablets 1-3 times a day.

Release form:

- tablets containing 250 mg of paracetamol, 150 mg of propyphenazone and 50 mg of caffeine.

ALKA-SELTZER

Ingredients: , citric acid, sodium bicarbonate. It is a well-absorbed soluble dosage form of aspirin with improved organoleptic properties. Sodium bicarbonate neutralizes free hydrochloric acid in the stomach, reducing the ulcerogenic effect of aspirin. In addition, it may enhance the absorption of aspirin.

It is mainly used for headaches, especially in people with hyperacidity in the stomach.

Dosage

Release form:

- "effervescent" tablets containing 324 mg of aspirin, 965 mg citric acid and 1625 mg sodium bicarbonate.

FORTALGIN C

The drug is an "effervescent" tablet, each containing 400 mg and 240 mg of ascorbic acid. It is used as an analgesic and antipyretic.

Dosage

1-2 tablets up to four times a day.

PLIVALGIN

Available in the form of tablets, each of which contains 210 mg and 50 mg of caffeine, 25 mg of phenobarbital and 10 mg of codeine phosphate. The analgesic effect of the drug is enhanced due to the presence of the narcotic analgesic codeine and phenobarbital, which has sedative effect. The role of caffeine is discussed above.

Indications

Pain of various localization (headache, dental, muscular, articular, neuralgia, dysmenorrhea), fever.

Warnings

With frequent use, especially at an increased dose, there may be a feeling of fatigue, drowsiness. Perhaps the development of drug dependence.

Dosage

1-2 tablets 3-4 times a day.

Rheopirin (Pyrabutol)

The composition includes ( amidopyrine) and ( butadione). It has been widely used as an analgesic for many years. However, he no performance advantage before modern NSAIDs and significantly surpasses them in the severity of adverse reactions. Especially high risk of developing hematological complications therefore it is necessary to observe all the above precautions () and strive to use other analgesics. When administered intramuscularly, phenylbutazone binds to the tissues at the injection site and is poorly absorbed, which, firstly, delays the development of the effect and, secondly, is the cause of the frequent development of infiltrates, abscesses, and lesions of the sciatic nerve.

Currently, the use of combined preparations consisting of phenylbutazone and aminophenazone is prohibited in most countries.

Dosage

Adults: inside 1-2 tablets 3-4 times a day, intramuscularly 2-3 ml 1-2 times a day.
In children does not apply.

Release forms:

- tablets containing 125 mg of phenylbutazone and aminophenazone;
- 5 ml ampoules containing 750 mg of phenylbutazone and aminophenazone.

BARALGIN

It is a combination ( analgin) with two antispasmodics, one of which - pitophenone - has a myotropic, and the other - fenpiverinium - atropine-like action. It is used to relieve pain caused by spasm of smooth muscles (renal colic, hepatic colic, and others). Like other drugs with atropine-like activity, it is contraindicated in glaucoma and prostate adenoma.

Dosage

Inside, 1-2 tablets 3-4 times a day, intramuscularly or intravenously, 3-5 ml 2-3 times a day. Intravenously administered at a rate of 1-1.5 ml per minute.

Release forms:

- tablets containing 500 mg of metamizole, 10 mg of pitofenone and 0.1 mg of fenpiverinium;
- 5 ml ampoules containing 2.5 g of metamizole, 10 mg of pitofenone and 0.1 mg of fenpiverinium.

ARTROTECH

It also consists of misoprostol (a synthetic analogue of PG-E 1), the inclusion of which aims to reduce the frequency and severity of adverse reactions characteristic of diclofenac, especially gastrotoxicity. Artrotek is equivalent to diclofenac in terms of effectiveness in rheumatoid arthritis and osteoarthrosis, and the development of erosions and stomach ulcers with its use is much less common.

Dosage

Adults: 1 tablet 2-3 times a day.

Release form:

- tablets containing 50 mg of diclofenac and 200 mg of misoprostol.

BIBLIOGRAPHY

1. Champion G.D, Feng P.H, Azuma T. et al. NSAID-induced gastrointestinal damage // Drugs, 1997, 53: 6-19.
2. Laurence D.R., Bennett P.N. Clinical Pharmacology. 7th ed. Churcill Livingstone. 1992.
3. Insel P.A. Analgesic-antipyretic and antiinflammatory agents and drugs employed in the treatment of gout. In: Goodman & Gilman's. The pharmacological basis of therapeutics. 9th ed. McGraw-Hill, 1996, 617-657.
4. Non-steroidal anti-inflammatory drugs. (Editorial article) // Klin. pharmacol. i pharmacoter., 1994, 3, 6-7.
5. Loeb D.S., Ahlquist D.A., Talley N.J. Management of gastroduodenopathy associated with the use of nonsteroidal anti-inflammatory drugs // Mayo Clin. Proc., 1992, 67: 354-364.
6. Espinosa L., Lipani J., Poland M., Wallin B. Perforations, ulcers and bleeds in a large, randomized, multicenter trial of namubetone compared with diclofenac, ibuprofen, naproxen and piroxicam // Rev. Esp. Reumatol., 1993, 20 (suppl. I): 324.
7. Brooks P.M., Day R.O. Nonsteroidal antiinflammatory drugs – differences and similarities // N. Engl. J. Med., 1991, 324: 1716-1725.
8. Lieber C.S. Medical disorders of alcoholism // N. Engl. J. Med., 1995, 333: 1058-1065.
9. Guslandi M. Gastric toxicity of antiplatelet therapy with low-dose aspirin // Drugs, 1997, 53: 1-5.
10. Applied Therapeutics: The clinical use of drugs. 6th ed. Young L.Y., Koda-Kimble M.A. (Eds). Vancouver. 1995.
11. Drugs of choice from the Medical Letter. new york. Revised ed. 1995.
12. Marcus A.L. Aspirin as prophilaxis against colorectal cancer // N. Engl.J. Med., 1995, 333: 656-658
13. Noble S, Balfour J. Meloxicam // Drugs, 1996, 51: 424-430.
14. Konstan M.W., Byard PJ., Hoppel C.L., Davis P.B. Effect of high dose ibuprofen in patients with cystic fibrosis // N. Engl. J. Med., 1995, 332: 848-854.
15. Perneger T.V., Whelton P.K., Klag MJ. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal anti-inflammatory drugs // N. Engl. J. Med, 1994, 331: 1675-1712.
16. Merck Manual of Diagnosis and Therapy. 16th ed. Berkow R. (Ed.). Merck & Co Inc., 1992.
17. Gillis J.C., Brogden R.N. Ketorolak. A reappraisal of its pharmacodinamic and pharmacokinetic properties and therapeutic use in pain management // Drugs, 1997, 53: 139-188.

2000-2009 NIIAH SGMA

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Non-steroidal anti-inflammatory drugs are a group of medicines widely used in medical practice. Their popularity in the treatment of various diseases is due to the pronounced ability to eliminate pain, temperature and foci of inflammation with high safety for the body. The analgesic and anti-inflammatory activity of NVPS has been proven by numerous medical tests.

They are more effective than "simple" painkillers, and some drugs are close in strength to centrally acting analgesics and opioids.

Mechanisms of action of NSAIDs

The main mechanism of action of NSAIDs, which characterizes their effectiveness and toxic effects, is inhibition of cyclooxygenase activity. It is an enzyme that regulates the conversion of arachidonic acid to prostaglandins, thromboxane and prostacyclin. The anti-inflammatory effect of NSAIDs may also be due to a slowdown in fat peroxidation, stabilization of the lysosome membrane, a decrease in ATP synthesis, a slowdown in neutrophil aggregation, and inhibition of the formation of rheumatoid factor in people suffering from rheumatoid arthritis.

Historical facts

The beginning of the use of non-steroidal anti-inflammatory drugs refers to 46-377 years. BC e., when Hippocrates used willow bark for pain relief and mitigation of inflammation. This fact on own experience was confirmed by Celsius in the 30s. n. e. Further mention of the properties of the bark dates back to 1763, and in 1827, when chemists managed to isolate from natural material Chemical substance, which turned out to be salicin, a precursor to NSAIDs.

Ask your question to a neurologist for free

Irina Martynova. Graduated from the Voronezh State medical University them. N.N. Burdenko. Clinical intern and neurologist of BUZ VO \"Moscow Polyclinic\".

In 1869, salicylic acid was obtained - a more effective substance, which is a derivative of salicin. After the experiments, it became clear that it can damage the gastric mucosa, and scientists began to search for new, safer means. In 1897, the Bayer company and the scientist Felix Hoffman converted the toxic salicylic acid into acetylsalicylic acid. The drug was named Aspirin.

For a long time, aspirin was the only NSAID compound, but since 1950, pharmacologists have received new drugs from the NSAID group, which have become more effective and safer than the previous ones.

Steroid and non-steroidal - differences

To eliminate edema, non-steroidal drugs are also used in medicine. Steroids are produced on the basis of glucocorticoids - hormones of the adrenal glands. Non-steroidal anti-inflammatory drugs have similar effectiveness, but their difference lies in the fact that they do not have characteristic pronounced side effects in the form of hypertension, the development of diabetes mellitus, and do not cause addiction to the body, requiring each time to increase the dosage to achieve a similar effect.

What are the release forms?

NSAIDs are available both in the form of capsules and tablets for oral administration, and in the form of ointments, suppositories, gels and injection solutions. This diversity allows more efficient use of the drug. The use of drugs in the form of injections minimizes the negative effects of drugs on the gastrointestinal tract, but at the same time can cause tissue necrosis.

For this reason, NSAID injections are never used for a long time.

Classification

To date, several dozen drugs are produced in the world, which include selective and non-selective NSAIDs, but in Russia only a part of them have been registered and are used. Their classification can be presented as follows:

By chemical structure:

• Salicylates are the oldest group, of which only Aspirin (acetylsalicylic acid) is currently used;
• Propionic acid derivatives - Ketoprofen, Ibuprofen, Naproxen;
• Acetic acid derivatives - Diclofenac, Indomethacin, Aceclofenac, Ketorolac;
• Pyrazolidins - Phelilbutazone, Analgin, Metamizole sodium;
• Selective COX-2 inhibitors are considered the safest agents, of which only Rofecoxib and Celecoxib are used in Russia;
• Non-acidic - sulfonamides, alkanones;
• Other NSAIDs, which include Mefenamic acid, Piroxicam, Nimesulide, Meloxicam.

Quite often, the list of non-steroidal anti-inflammatory drugs is included, which has analgesic and antipyretic effects, but in fact the drug is not included in this group. Its anti-inflammatory activity is very weak, and its analgesic and antipyretic effect is due to the blocking of COX-2 in the central nervous system.

By efficiency. The following painkillers have the most pronounced effect: Diclofenac, Indomethacin, Ketoprofen, Ketorolac. Ibuprofen has the least pronounced analgesic effect. Piroxicam, Indomethacin, Diclofenac, Piroxicam relieve inflammation as quickly as possible. Aspirin, Nise and Nurofen are able to quickly remove the temperature.

New generation drugs. They were created in order to reduce the side effects of drugs of this class on the body. Such drugs are Movalis and Piroxicam, Nise, Arcoxia, which, in addition to selective action, have a prolonged elimination period (long excreted), thereby enhancing the therapeutic effect.

For the treatment of joints

Used as a base drug therapy, especially in the acute stage of the disease, quickly relieving pain, swelling and inflammation. For this use:

• in the form of an ointment. The action of the agent is similar to preparations containing, but has a lower efficiency and a pronounced warming effect. Contraindicated in ulcers in the gastrointestinal tract, pregnancy and lactation, bronchial asthma. Price - 43-344 rubles.
• - An analogue of Diclofenac with antipyretic, anti-inflammatory and analgesic effects. It is used for inflammatory diseases of the OP. Contraindicated in the "aspirin triad", hypersensitivity, erosive and ulcerative diseases and bleeding in the gastrointestinal tract, diseases of the liver and kidneys, pregnancy, childhood, hyperkalemia and after coronary artery bypass grafting. Price - 134-581 rubles.
• - has an auto-aggregate effect, effectively relieves pain and fever. Contraindicated in erosive and ulcerative diseases of the gastrointestinal tract, disorders of porphyrin metabolism, diseases of the liver and kidneys, pregnancy and lactation, under the age of 14 years and hypersensitivity. Price - 35-89 rubles.

At

The following non-steroidal anti-inflammatory drugs are used:

1. . It has a pronounced anti-inflammatory, analgesic, and moderate antipyretic effect, it is successfully used for spinal hernia. Contraindicated in ulcers and erosions in the gastrointestinal tract, pregnancy and lactation, allergies caused by taking NSAIDs. Price - 14-75 rubles.
2. . NSAIDs of a new generation, available in the form of tablets, suppositories and injections, are practically devoid of side effects. Price - 502-850 rubles.
3. . It has a strong anti-inflammatory, moderate analgesic and mild antipyretic effect. Contraindicated in ulcers and bleeding in the gastrointestinal tract, renal and hepatic insufficiency, pregnancy and lactation, under the age of 12 years and hypersensitivity. Price - 126-197 rubles.

With a hernia of the spine

In case of protrusion of the intervertebral disc, the following drugs are used for hernia:

1. - effectively relieves fever and pain, has a slight anti-inflammatory effect. Contraindicated in leukopenia, severe anemia, hepatic and renal insufficiency and hypersensitivity to the drug. Price - 345-520 rubles.
2. - has a pronounced analgesic, antipyretic and anti-inflammatory effect, blocks the enzyme involved in inflammatory processes. Contraindicated in peptic ulcers, renal and hepatic insufficiency, "aspirin triad" and hypersensitivity. Price - 502-850 rubles.
3. - the basic drug used in diseases of the musculoskeletal system, has anti-inflammatory, antipyretic and analgesic effects in spinal hernia. Contraindicated in erosive lesions in the gastrointestinal tract, "aspirin triad", pregnancy, hepatic and renal insufficiency, oppression of hematopoiesis, in childhood and with hypersensitivity reactions. Price 121-247 rubles.

At

1. . It exhibits analgesic, anti-inflammatory, antipyretic properties that can relieve a neuralgic attack, inhibits platelet adhesion. Contraindicated in ulcers in the gastrointestinal tract, severe disorders of the liver and kidneys, pregnancy, breastfeeding and in childhood, hypersensitivity. Price - 44-125 rubles.
2. Nise. Nimesulide, which is part of the composition, has antipyretic, anti-inflammatory, analgesic and antiplatelet effects. Contraindicated in acute ulcerative manifestations and bleeding in the gastrointestinal tract, severe disorders of the liver and kidneys, pregnancy and lactation, under the age of 2 years and intolerance to the drug. Price - 173-424 rubles.
3. . It has a pronounced analgesic, antipyretic, as well as a weak antispasmodic and anti-inflammatory effect. Contraindicated in hypersensitivity, oppression of hematopoiesis, liver or kidney failure, "aspirin" asthma, leukopenia, pregnancy and lactation, anemia. Price - 27-60 rubles.

With osteoarthritis

The following drugs are used:

1. , more often used in the form of an ointment, gel or cream, has an analgesic and anti-inflammatory effect, relieves swelling associated with inflammation. Contraindicated in hypersensitivity, allergic rhinitis, attacks of bronchial obstruction, pregnancy and lactation, violations of the integrity of the skin at the sites of application, at the age of up to 14 years and in conjunction with drugs, including phenylbutazone. Price - 119-206 rubles.
2. , is used as a new generation drug for arthrosis. It has analgesic, anti-inflammatory and antipyretic effects. Contraindicated in hypersensitivity, heart failure and arrhythmia, liver disease and stomach ulcers, leukopenia and pregnancy. Price 220-475 rubles.
3. . It has analgesic, anti-inflammatory and antipyretic effects. Contraindicated in erosive and ulcerative lesions in the gastrointestinal tract, "aspirin" asthma, rhinitis, urticaria caused by taking NSAIDs, severe impairment of kidney function, pregnancy and lactation, hypersensitivity. Price - 120-345 rubles.

For gout

The following NSAIDs are used:

1. , is produced in the form of tablets and ointments. The maximum effectiveness of the drug is ensured after the simultaneous use of both forms of the drug. It is forbidden for hypersensitivity, ulcerative bleeding, inflammatory diseases in the gastrointestinal tract, hyperkalemia, liver and kidney failure, pregnancy and lactation. Price - 173-380 rubles.
2. Other NSAIDs - Ibuprofen.

Cheap drugs

1. Ibuprofen (analogue). Price (tablets) - 14-26 rubles.
2. sodium (similar to Voltaren tablets). Price: tablets - 14-35 rubles, gel or ointment - 32-75 rubles.
3. Meloxicam (similar to Movalis tablets). Price - 31-84 rubles.
4. Acetylsalicylic acid (Aspirin). Price - 7-17 rubles.
5. Analgin. Price - 27-60 rubles.

Criterias of choice

All NSAIDs are modern and effective medicines, but when choosing a particular drug, you need to know some features. So, if you need to buy one of the three drugs -, or, the seller in the pharmacy will most likely offer a more expensive option, despite their identity with respect to the active substance. The situation is similar when choosing Indomethacin, or Metindol.

In addition to the identical active substance, when choosing an analogue of the agent, it is necessary to pay attention to the accompanying components, since the analogue of the usual drug may contain components that can cause an allergic reaction. Also, in the analogue of the drug there may be a different dosage of the active substance or a retarded form (long-acting).

All the features of the drug are indicated in the instructions or on the packaging, and before use it is subject to careful study.

Application

Since non-steroidal anti-inflammatory drugs can cause various side effects, the following rules must be followed before using them:

1. Mandatory familiarization and strict adherence to the recommendations set out in the instructions.
2. Capsules or tablets taken orally, be sure to drink a glass of water, which will protect the stomach. The rule applies, among other things, to the most modern means, which are the safest.
3. After taking the product inside, it is recommended not to take a supine position for at least 3 minutes, so that under the influence of gravity the capsule would better pass down the esophagus.
4. Simultaneous intake of drugs and alcohol-containing substances can provoke stomach diseases. At the time of the course of taking NSAIDs, alcohol is completely abandoned.
5. On the same day two nonsteroidal drugs it is not recommended to take, as this summarizes the side effects, and will not bring an increase in the action.
6. If the drug is ineffective, the doctor must be informed to find out the cause, adjust the dose and more carefully select the remedy.

Indications for use

NSAIDs are among the most commonly used drugs in medicine. So, they are assigned to 1/5 of the patients to eliminate pain and inflammation in diseases related to the following areas:

1. Rheumatology.
2. Gynecology.
3. Traumatology.
4. Surgery.
5. Dentistry.
6. Neurology.
7. With eye diseases.

The analgesic effect of NSAIDs is especially effective for:

1. Dysmenorrhea.
2. Pain syndrome of various origins - dental, head, muscular.
3. Migraine.
4. Renal colic.

The ability to reduce high temperature causes the use of drugs for "cold" diseases and in emergency situations when hyperthermia threatens a person's life. Then the drugs are administered parenterally as a means of emergency therapy. NSAIDs are widely used to treat sports injuries and treat complications from chemotherapy sessions.

Aspirin's ability to thin the blood has been used to prevent thrombosis.

NSAIDs are used in the treatment of various stages of inflammation, accompanied by pain. These pathologies include the following diseases:

1. and pain.
2. Acute and migraine.
3. Pain accompanying menstruation.
4. Rheumatoid arthritis and.
5. Pain in the bones with metastases.
6. Pain associated with Parkinson's disease.
7. Fever (feeling feverish).
8. Moderate pain after soft tissue injury or inflammation.
9. Intestinal obstruction.
10. Renal colic.
11. postoperative pain.

NSAIDs can be used to treat newborns who do not close the ductus arteriosus within 2 days after birth.

Contraindications

1. Ulcerative manifestations and the presence of bleeding in the stomach.
2. Uncontrolled arterial hypertension.
3. Kidney diseases.
4. Inflammation of the intestines.
5. Stroke, myocardial infarction and transient ischemic attack in the past, as well as cardiac ischemia (except Aspirin).
6. Bypass grafting of the coronary artery and stomach.
7. thrombocytopenia.

special instructions

With long-term use of NSAIDs, the state of the blood and the functioning of the liver and kidneys should be monitored, which is especially important for patients over 65 years of age. With extreme caution, funds are used in patients suffering from high blood pressure, problems with the cardiovascular system, leading to fluid retention in the body.

It should be fate that this type of drugs is able to mask the symptoms of infectious diseases and affect the ability to concentrate.

What drugs are best for children?

NSAIDs can be used in childhood for the treatment of inflammatory processes accompanied by swelling, high fever, inflammation of the lymph nodes and painful sensations. Means should be used with extreme caution, as they can cause irritation of the gastric mucosa, allergies, problems with breathing, vision and hearing, internal bleeding.

During treatment inflammatory diseases in children, Mefenamic acid is used and due to the absence of a serious side effects, but at the same time they can provoke indigestion or constipation. To eliminate foci of inflammation and temperature, use Aspirin.

Prescribing medications is done only by a doctor who carefully adjusts the dosage to prevent possible side effects.

disadvantages

The main disadvantage of non-steroidal anti-inflammatory drugs is is gastrointestinal toxicity. Prostaglandins belonging to group E play a major role in gastroduodenal protection. With a decrease in the concentration of prostaglandins in the gastric mucosa under the influence of drugs, this protection is violated, causing ulcers, erosions and other lesions. Under the influence of NSAIDs, a stomach ulcer develops in 30% of cases. They also have a destructive effect on the duodenal mucosa, increasing the risk of ulcers, perforations and bleeding in it.