Nonsteroidal anti-inflammatory drugs (NSAIDs)

Fundamental effects of drugs

All representatives of the nonsteroidal anti-inflammatory drugs group possess the classical clinical triad. The severity of each of these properties may vary depending on a specific active substance, but three components are always at the core:

1. Anti-inflammatory effect — suppression of tissue reactions in the lesion focus.
2. Analgesic (pain-relieving) effect — reduction of pain perception primarily at the peripheral level.
3. Antipyretic (fever-reducing) effect — normalization of body temperature in febrile conditions.

The basic mechanism uniting these seemingly disparate effects lies in the ability of NSAIDs to interfere with the synthesis of key mediators of the inflammatory process — prostaglandins (primarily E2 and I2 fractions).

Pathophysiological role of prostaglandins

To fully understand how drugs of this group work, it is necessary to examine in detail what prostaglandins do in the body during the development of an inflammatory reaction. These molecules act as peculiar "conductors" of the pathological process.

• Vascular reactions and edema: Prostaglandins provoke pronounced arteriolar dilation. In addition, they act as powerful synergists — they potentiate (multiply enhance) the effect of other inflammatory mediators, such as histamine and bradykinin, on the vascular wall. As a result of this pathological interaction, vascular permeability increases sharply. Plasma extravasation occurs — the liquid part of the blood goes beyond the vascular bed, which inevitably leads to tissue infiltration and the formation of pronounced inflammatory edema.
• Formation of pain syndrome (nociception): Prostaglandins do not cause pain by themselves, but they critically increase the sensitivity (sensitize) of peripheral pain receptors to the irritating chemical effects of histamine and bradykinin.
• Impaired thermoregulation: Prostaglandin E2 has the ability to affect central structures of the brain. It directly stimulates the thermoregulation center located in the hypothalamus, which leads to a systemic increase in body temperature (fever).

Biochemical mechanism of action of NSAIDs

The pharmacological action of nonsteroidal anti-inflammatory drugs is realized at a strictly defined stage of the biochemical cascade. The process of inflammatory mediator formation is as follows:

1. The initial substrate for synthesis is arachidonic acid, which is released from cell membranes.
2. The key enzyme comes into play — cyclooxygenase (COX).
3. Under the catalytic action of COX, arachidonic acid is transformed into intermediate products — cyclic endoperoxides. These are extremely unstable chemical compounds.
4. Active prostaglandins (including E2 and I2) as well as thromboxane are ultimately synthesized from cyclic endoperoxides.

The point of application of NSAIDs is inhibition of the cyclooxygenase enzyme. The medicinal product reliably blocks this enzyme, breaking the biochemical chain at the stage of arachidonic acid transformation. As a direct consequence, the synthesis of prostaglandins E2 and I2 ceases. The clinical outcome of such blockade is the powerful realization of the entire spectrum of declared effects: edema subsides, pain goes away, and temperature normalizes.

Clinical application: from inflammation to pure pain

The range of NSAID prescriptions in medical practice is extremely wide. Their application can be roughly divided into two large categories depending on the leading clinical syndrome.

Treatment of inflammatory-origin diseases Drugs are used where a powerful combination of anti-inflammatory and analgesic properties is required. The main indications are disorders of the musculoskeletal system and nervous system:

• Various forms of arthritis.
• Myositis (inflammation of muscle tissue).
• Neuritis.

In these cases, the drugs of choice are often acetylsalicylic acid (Aspirin), ibuprofen (Brufen), and diclofenac (Voltaren).

Use as painkillers NSAIDs are frequently prescribed as pure analgesics to relieve pain syndrome in the mechanism of which prostaglandins are also involved. Classical examples are the relief of headaches (traditionally acetylsalicylic acid is used) and the treatment of dysmenorrhea (pain associated with menstruation).

It is important to note that in the classification there is a separate subgroup of predominantly peripheral action drugs, which includes metamizole sodium and ketorolac. These medicinal products conceptually stand out from the general mass of NSAIDs in that in clinical practice they are used almost exclusively as powerful pain relievers, while their anti-inflammatory potential takes a backseat.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Structure and metabolism of arachidonic acid
• Cyclooxygenase isoforms (COX-1 and COX-2)
• Mechanisms of action of thromboxane
• Specific side effects of metamizole sodium
• Neurophysiology of nociception and the role of bradykinin

Other topics in the "Analgesics" section

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