CHEMICAL COMPOUNDS NSAIDs

Most of the NSAIDs are organic acids but they form a heterogeneous group of compounds with few further chemical relationships. At least 10 different groups can be distinguished. Some of the most frequently used groups are listed in Table 3. The prototype is aspirin and therefore the term aspirin-like drugs is frequently used. 

Some of the popularly used anti-inflammatory drugs, such as paracetamol, are not an NSAID but have analgesic/antipyretic properties. Paracetamol specifically has relatively weak anti-inflammatory activity. Once excreted, it gets reactivated in the environment through some microbially mediated transformation (Henschel et al., 1997). The exact mechanisms by which paracetamol relieves pain are not very clear. It has a chemical structure that resembles several estronegic compounds. 

The SFC separation of nonsteroidal anti-inflammatory drugs (NSAIDs) was investigated by Jagota and Stewart [6]. These compounds vary in chemical structure and functional group chemistry and provide a representative sample of acidic drugs to study. Using a 10-m x 50-fim ID... 

These early studies led to extensive efforts by many laboratories to develop selective inhibitors of the COX-2 isoform with the goal of developing an ideal NSAID—that is, one that selectively inhibits COX-2, thus reducing the inflammatory response but not interfering with the Gl-protective functions of COX-1. Two early lead compounds were developed, NS-398 and DuP 697, which have served as the basis of the development of two widely explored chemical classes. NS-398 and nimesulide are the prototypes of compounds known as sulides, ... 

Since platelets have no DNA, they are unable to synthesise new COX once aspirin has irreversibly inhibited the enzyme. Other NSAlDs cyclooxygenase inhibitors such as ibuprofen, diclofenac, and indomethacin act similarly to aspirin in that they bind to COX but they do not covalently modify the enzjtme and thus do not irreversibly inhibit the platelet function (Fig. 14.11). NSAID analgesics can be chemically classified as shown in Table 14.2. Ibuprofen was the first of these compounds to be marketed and it was followed by a number of other compounds such as naproxen and ketoprofen, which are more potent than ibuprofen. 

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