Nonsteroidal Antiinflammatory Drugs

Organic Health Protocol

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are symptomatic agents used in many rheumatic conditions, including RA. They have analgesic and also anti-inflammatory properties and are effective in the relief of inflammatory symptoms and signs, such as joint stiffness, swelling, and tenderness. They also have a widening range of uses outside of rheumatology: for example, these agents are used for dysmenorrhoea, renal colic, and postoperative pain. In contrast to many of the drugs that will be reviewed later, NSAIDs do not fundamentally alter the underlying course of such diseases as RA. A large number of NSAIDs are currently available and these agents are derivatives of different acidic compounds, such as salicylic acid, acetic acid, and propionic acid (17). As a result of their variable chemical structure, there is significant variability in many of the pharmacokinetic properties of NSAIDs. For example, the elimination of naproxen and ketoprofen is significantly reduced by renal impairment, whereas sulindac and pirox-icam are less influenced by renal impairment (17).

Despite variability in their chemical structure and pharmacokinetics, NSAIDs mediate their principal anti-inflammatory effects by inhibiting the cyclo-oxygenase (COX) enzyme system. This is a key enzyme in the production of proinflammatory pros-taglandins from phospholipids and arachadonic acid (Fig. 1). Recently, it has been noted that there are two distinct forms of the COX enzyme. COX-1 is a constitutive enzyme, which is important in the production of prostaglandins for physiological purposes, such as maintenance of the acid barrier in the stomach and also in the control of renal blood flow and sodium excretion. COX-2, in contrast, is an inducible enzyme, production of which is upregulated by proinflammatory cytokines, such as IL-1 and TNF-a (17). The production of prostaglandins by this mechanism is increased at sites of inflammation,

Cell membrane phospholipids phospholipase

Figure 1 Summary of prostaglandin synthetic pathway and the role of COX enzymes. The COX-1 and COX-2 enzymes (gray boxs) are inhibited to a variable degree by most NSAIDs. Abbreviations: COX, cyclo-oxygenase; NSAIDs, nonsteroidal anti-inflammatory drugs.

such as the rheumatoid synovium. In recent years, several new NSAIDs have been developed, which selectively or specifically inhibit the inducible COX-2 enzyme. These agents are associated with a reduced risk of certain complications, particularly peptic ulceration and its consequences (18,19).

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