Overview Of Anti-Inflammatory Drugs

Inflammation is a response of tissue damage that brings several biochemical mediators such as histamine, bradykinin, platelet-activating factor, and a group of lipid material known as leukotrienes (LTs) and prostaglandins (PGs) from the circulation to the sites where they are needed, to eliminate the offending agents. These mediators are responsible for the symptoms that accompany the inflammation process. While histamine, bradykinin, and leukotrienes cause the swelling and redness of the inflamed area (due to vasodilation and increased capillary), prostaglandins, on the other hand, increase tissue sensitivity to pain and cause elevation of body temperature. Although inflammation suggests a harmful reaction, it is in actual a protective response that is essential for survival.

The importance of eicosanoids in inflammation has driven attempts to develop drugs that inhibit their productionor actions and thus suppress inflammation. These anti-inflammatory drugs include the following:

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely prescribed drugs in the treatment of pain and inflammation in many conditions, including osteoarthritis and rheumatoid arthritis. The mechanism of action of NSAIDs involves blockage of prostaglandin synthesis by inhibiting both isoforms of cyclooxygenase enzyme (COX-1 and COX-2) through competitive antagonism for arachidonic acid binding to the cyclooxygenase enzymes (COX). The drug possesses both high lipophilic and acidic properties to mimic the natural substrate chemistry for it to be an effective competitive inhibitor for arachidonic acid. Conventional NSAIDs are nonselective that bind and inhibit both isoforms but COX-1 is inhibited more avidly than COX-2. Inhibition of COX-1 is responsible for side effects and of COX-2 for therapeutic effects. This has resulted in the introduction of the COX-2 selective drugs. These are the newer drugs that have recently been made available in the market and are 200- to 300-fold more potent in blocking COX-2 than COX-1. Their examples include nimesulide, nabumatone, meloxicam, etodolac, celecoxib, and rofecoxib. Last two have especially become popular amongst clinicians. These are generally considered to be safer and more tolerable and equally efficacious.

Lipoxygenase inhibitors : 5-lipoxygenase is not affected by NSAIDs. 5-lipoxygenase inhibitors prevent leukotriene synthesis. Leukotriene receptor antagonists block the CysLT1 receptors on airway smooth muscle and other cells. These drugs have some anti-inflammatory effects and a modest short-acting bronchodilator effect. Pharmacologic agents that inhibit leukotriene production (e.g., zileuton) are useful in the treatment of asthma.

Corticosteroids are broad-spectrum anti-inflammatory agents that reduce the transcription of genes encoding COX-2, phospholipase A2, proinflammatory cytokines (e.g., IL-1 and TNF), and iNOS.

Leukotriene receptor antagonists block leukotriene receptors and prevent the actions of the leukotrienes. These drugs (e.g., Montelukast) are useful in the treatment of asthma.