NSAIDs Classification and Mechanism of Action Explained

NSAIDs: Therapeutic Groups

NSAIDs are categorized into three primary therapeutic groups:

• Analgesic
• Antipyretic
• Anti-inflammatory

Classification of NSAIDs

A. Nonselective COX Inhibitors (Traditional NSAIDs)

• Salicylates: Aspirin
• Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen, Flurbiprofen
• Anthranilic acid derivative: Mefenamic acid
• Aryl-acetic acid derivatives: Diclofenac, Aceclofenac
• Oxicam derivatives: Piroxicam, Tenoxicam
• Pyrrolo-pyrrole derivative: Ketorolac
• Indole derivative: Indomethacin
• Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone

B. Preferential COX-2 Inhibitors

• Nimesulide, Meloxicam, Nabumetone

C. Selective COX-2 Inhibitors

• Celecoxib, Etoricoxib, Parecoxib

D. Analgesic-Antipyretics (Poor Anti-inflammatory Action)

• Para-aminophenol derivatives: Paracetamol
• Pyrazolone derivatives: Metamizole, Propiphenazone
• Benzoxazocine derivative: Nefopam

Mechanism of Action

1. Anti-inflammatory Effect

The anti-inflammatory effect is due to the inhibition of enzymes that produce prostaglandin H synthase (cyclooxygenase, or COX), which converts arachidonic acid to prostaglandins, TXA2, and prostacyclin.

Note: Aspirin irreversibly inactivates COX-1 and COX-2 by acetylation of a specific serine residue, distinguishing it from other NSAIDs that inhibit these enzymes reversibly.

2. Analgesic Effect

• Peripheral inhibition: NSAIDs inhibit prostaglandin production peripherally and may inhibit pain stimuli at subcortical sites.
• Mediator suppression: They prevent the potentiating action of prostaglandins on endogenous mediators of peripheral nerve stimulation (e.g., bradykinin).

3. Antipyretic Effect

The antipyretic effect is believed to be related to:

• Inhibition of prostaglandin production induced by interleukin-1 (IL-1) and interleukin-6 (IL-6) in the hypothalamus.
• The "resetting" of the thermoregulatory system, leading to vasodilatation and increased heat loss.

Focus: Salicylates (Aspirin)

Aspirin (Acetylsalicylic acid) is converted to salicylic acid in the body, which is responsible for its therapeutic action.