Nonsteroidal anti-inflammatory drugs: the view of a clinical pharmacologist

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs, or NSAIDs, are analgesics that exhibit three effects: analgesic, antipyretic and anti-inflammatory. At the same time, the notoriety about the bad effect of these drugs on the stomach literally haunts them.

We will understand the features of the principle of action, indications and, of course, the safety of NSAIDs in the second article in the series on analgesic drugs.

NSAIDs include:

• salicylates - acetylsalicylic acid;
• pyrazolones - analgin;
• derivatives of organic acids - ibuprofen, naproxen, ketoprofen, indomethacin, ketorolac, aceclofenac, diclofenac, piroxicam, meloxicam, mefenamic acid, etc.;
• coxibs - celecoxib, rofecoxib, parecoxib, etoricoxib.

Acetylsalicylic acid: an analgesic with experience

Few people know that the very first NSAID, acetylsalicylic acid, is of plant origin - its predecessor was obtained from meadowsweet, or meadowsweet. The drug was created by Bayer pharmacists at the end of the 19th century and named it after the Latin name for the meadowsweet Spiraea ulmaria aspirin.

The principle of action of aspirin, like all other NSAIDs, is to block the enzyme cyclooxygenase (COX). There are two types of COX in the body. The first, COX-1, is a necessary, “good” enzyme: it performs many important functions, including protecting the gastric mucosa. The second, COX-2, is responsible for the production of prostaglandins, triggering the mechanism of pain and inflammation.

Acetylsalicylic acid blocks both types of COX, with the first type of enzyme to a greater extent than the second. Therefore, the list of its side effects is considerable, and the leader in it is damage to the gastric mucosa, which can lead to the development of gastritis and even peptic ulcers. Aspirin is strictly contraindicated in children under 15 years of age due to the risk of developing Reye's syndrome - severe damage to the brain and liver.

Adults can take the drug as an antipyretic and mild pain reliever. However, in recent years, acetylsalicylic acid in this field has given way to safer NSAIDs and has become a cardiac drug due to its property of preventing platelet aggregation and thus “thinning” the blood.

Doubtful analgin?

Metamizole sodium, or analgin, is a fairly active pain reliever and a very weak anti-inflammatory drug. It is loyal to the stomach, directing all its negative influence on the blood. A serious side effect of analgin is the ability to change the blood picture and lead to the development of aplastic anemia, agranulocytosis and other hematological troubles.

In many countries of the world, including the USA, analgin is prohibited for sale. But in Germany, for example, it is widely used and is even considered the drug of choice for the treatment of postoperative pain. In Russia, they know, love and drink analgin, and, frankly, there is nothing wrong with it - the main thing is not to consume it regularly (that is, day after day) and not to exceed the recommended doses.

Diclofenac associates

The group of acid derivatives amazes even specialists with their choice, but each drug included in it still has its own “face”. Derivatives of organic acids are distinguished by pronounced anti-inflammatory properties, often overshadowing the analgesic and antipyretic effect. The exception is ibuprofen, which is still most often used to combat pain and fever, rather than inflammation.

Indomethacin and diclofenac are considered one of the most powerful anti-inflammatory drugs in this subgroup. The first has an adverse effect on the stomach and blood, and is rarely used today. Diclofenac is much safer, which, coupled with high activity and cost-effectiveness, ensures extremely high popularity in rheumatic diseases.

However, in terms of analgesic effect, diclofenac is significantly inferior to many drugs, in particular naproxen, which is successfully used to combat various types of intense pain, including dental, headache, periodic, etc. Naproxen is sold without a prescription and is in demand as quite safe, an affordable and yet powerful analgesic.

Another NSAID used for pain relief is ketorolac, known by the trade name Ketanov. It is distinguished by its speed, strength and duration of analgesic action in combination with gastrointestinal side effects traditional for NSAIDs. Therefore, ketorolac is used only with a doctor’s prescription to relieve postoperative pain, pain due to cancer and in other difficult cases.

Mefenamic acid is much more innocent than ketorolac, but is not as effective. Its reputation as an effective antipyretic agent is somewhat exaggerated: the drug is slightly more active than acetylsalicylic acid.

And another representative of NSAIDs that cannot be ignored is meloxicam, which combines a rather gentle effect on the stomach with a powerful anti-inflammatory effect, due to which it is often used in rheumatology.

Coxibs: the last word in pharmacology

Coxibs are the youngest group of NSAIDs, the first representative of which, celecoxib, went on sale in the late 1990s. Coxibs have almost no effect on COX-1, and therefore have virtually no gastrointestinal side effects traditional for this group. They adequately fight pain and inflammation in arthritis and other rheumatoid diseases, but they did not live up to the initial expectations that specialists had when the first coxib appeared.

Drugs in this group are still not without side effects (in particular, experts are still discussing the possible effect of coxibs on increasing the risk of heart attack and stroke) and, moreover, have a rather high price, which can pull the rug out from under already unhealthy legs. The decision to prescribe them should only be made by a doctor, and self-medication with coxibs, as well as most other NSAIDs, should not be done.

To readers who are still tormented by the agony of choice, I would like to say: do not be tormented. Get rid of this stone on your soul by placing it on the shoulders of your doctor. Trust him with your pain and inflammation and don’t test your stomach trying to hit the roof and find the “best” NSAID from dozens of medications.

Marina Pozdeeva

Photo thinkstockphotos.com

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Risk of adverse drug reactions when using NSAIDs

Since the effectiveness of NSAIDs in therapeutic doses is comparable, when choosing NSAIDs for a particular patient, we proceed from the possible risks of developing ADRs (Table 1) [1]. Risk factors for the development of ADRs when using NSAIDs are: age over 60 years, overweight, smoking, history of gastric and duodenal ulcers, history of venous thrombosis and thromboembolism, coronary artery disease, cerebrovascular disease, peripheral atherosclerosis, arterial hypertension, lipid metabolism disorders , diabetes mellitus, diseases of the intestines, liver, kidneys, blood, congestive heart failure, chronic alcohol intoxication, combined use of medications that interact with NSAIDs, lactation. For a more differentiated selection of NSAIDs, a special algorithm was proposed, which involves the prescription of selective NSAIDs to patients with risk factors for developing gastrointestinal complications and the use of NSAIDs with a less pronounced toxic effect on the cardiovascular system in patients with high cardiovascular risk, as well as the prescription protective therapy (Table 2) [1].

According to Russian recommendations for the rational use of NSAIDs:

• the main method of preventing the development of ADRs when using NSAIDs is taking into account risk factors, their correction (if possible) and prescribing NSAIDs with a more favorable gastrointestinal (recommendation grade A) and cardiovascular safety profile (recommendation grade B);
• an additional method of preventing complications from the upper gastrointestinal tract is the prescription of proton pump inhibitors (PPIs) (grade of recommendation A);
• an additional method for preventing complications from the upper gastrointestinal tract, small and large intestine can be the prescription of rebamipide (gradation of recommendation B);
• There are no effective drug methods of nephro- and hepatoprotection to reduce the risk of NSAID-associated complications.

Adjuvant pain therapy – what is it?

The most important thing in the treatment of any disease is to eliminate not the symptoms of the disease, but the causes of its development. However, not all diseases require etiotropic therapy, for example, cancer and autoimmune diseases. That is why in medicine and pharmacology there are drugs for the pathophysiological and symptomatic treatment of diseases.

Depending on the intensity of pain, the doctor prescribes patients either narcotic medications or non-steroidal anti-inflammatory drugs. To increase the chances of treatment success, various combinations are used, but often the analgesic effect of the drugs is reduced.

Adjuvant therapy is the treatment of diseases using medications that take into account their symptoms, for example, glucocorticosteroids. These highly effective drugs can affect several symptoms of the disease at once, as well as eliminate possible negative consequences for the body and reduce the level of pain. This helps specialists control and more accurately calculate the dose of pain medications, minimizing side effects.

In the treatment of chronic pain syndrome, a fairly wide range of drugs is used, including steroidal anti-inflammatory drugs and many other medications. Depending on the type of pain, its location and clinical picture, doctors use both anti-inflammatory steroid drugs and painkillers, anticonvulsants, antispasmodics and even antidepressants.

Quite often, steroidal anti-inflammatory drugs are used to treat joints, the list of them is quite wide.

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Indications for use

Medications that have anti-inflammatory effects have a fairly extensive list of side effects. Glucocorticosteroids are used in the following situations:

• elimination of allergic reactions when taking the medicine (painkiller) for the first time;
• elimination of nausea and vomiting that occurs from taking narcotic analgesics;
• compression of nerves and spinal cord (osteochondrosis);
• increased intracranial pressure;
• increased appetite in people with various diseases;
• during tissue infiltration in oncology.

Anti-inflammatory steroid drugs are used in the treatment of rheumatoid arthritis and diseases of connective tissue and joints, to eliminate inflammation and relieve pain. In medical practice they are used for hypotension caused by shock or bleeding. In addition, steroid analgesics are used for adrenal dysfunction.

Mechanism of action

The mechanism of the anti-inflammatory action of NSAIDs is based on blocking the enzyme cycloxygenase, which is a mediator of one of the links in the inflammatory reaction cascade.

The analgesic effect of NSAIDs is based on reducing the sensitization of nerve endings to prostaglandins, which reduces the effect of irritants.

The antipyretic effect is associated with a decrease in the synthesis of prostaglandins, due to which they have less influence on the thermoregulation center of the hypothalamus.