Analgesics and Anti-Inflammatory Drugs

Consumption of analgesics and anti-inflammatory drags in other developed countries is also quite high as is reflected in Table 1.7. Most widely used almost across the board in those countries is acetylsalicyclic acid and paracetamol. Beyond these two, it is apparent that the pattern of use of the other pain medications is quite diverse, with some pain relievers more popular in some countries than in others. Although the statistics are not readily available, pain relief medications are also the most consumed per capita in developing countries. 

Analgesics and anti-inflammatories generally act based on the fact that inflammation increases the synthesis of cyclooxgenase (i.e., COX)-dependent prostaglandins, which in turn sensitizes receptor terminals, producing localized hypersensitivity to pain. 

Common NSAIDs include aspirin, ibuprofen, indomethacin, naproxen, and ketoprofen. Even though anti-inflammatories generally target cyclooxygenase, there are apparent differences in the details of how they relieve pain. For example, aspirin acts by primarily inhibiting the COX-dependent synthesis of eicosanoids, which are end products of metabolism of essential fatty acids including prostaglandin 

TABLE 1.7 Annual Consumption of Various Pain-Relief Medications in Europe and Australia 

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. 

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A simple compound to begin our presentation is acetylsalicylic acid (aspirin, 7.44), the well-known analgesic and anti-inflammatory drug whose primary metabolite, salicylic acid (7.45), is also an anti-inflammatory agent but not an analgesic. Extensive kinetic data have been published on the chemical hydrolysis of acetylsalicylic acid as a function of temperature and... 

Ibuprofen is a popular analgesic and anti-inflammatory drug. There are two stereoisomeric forms of ibuprofen. This drug can exist as (S)- and (/ )-stereoisomers (enantiomers). Only the (5)-form is active. The (/ )-form is completely inactive, although it is slowly converted in the body to the active (5)-form. The drug marketed under the trade names, commercially known as Advil , Anadin , Arthrofen , Brufen , Nurofen , Nuprin , Motrin etc., is a racemic mixture of (/ )- and (5)-ibuprofen. 

Arylpropionic analgesic and anti-inflammatory drugs 6. GABAergic agonists... 

NS AID prototype inhibits cyclooxygenase (COX)-l and -2 irreversibly. Potent antiplatelet agent as well as antipyretic analgesic and anti-inflammatory drug. Tox Gl ulcers, allergy, bronchoconstriction, salicylism. 

It is an analgesic and anti-inflammatory drug structurally very similar to tolmetin sodium. It is normally used in mild to moderate pain, ineluding that of musculoskeletal disorders. 

Several analgesic and anti-inflammatory drugs such as ibuprofen and naproxen belong to the general class of a-arylalkanoic acids. An often used synthetic route to these molecules is the C-C bond cleavage by Lewis acid catalyzed rearrangement of the ketals of aryl a-haloalkyl ketones (Rieu et al., 1986). Methods based on asymmetric catalysis have also been developed (see Chapter 9). It has recently been shown (Baldovi et al., 1992) that zinc-exchanged Y-zeolites can catalyze the transformation of the ethylene ketal (14) of 2-bromopropiophenone to the a-phenylpropanoic ester (15) (reaction 6.8). 

Analgesics and anti-inflammatory drugs form a heterogeneous group which cannot be systematically classified (Miller et al. 1978). On the basis of their chemical structure, however, they can be divided into the following classes (Wcx)dbury and Fingl 1979 Shen 1979) ... 

The exact mechanism for intolerance to azo dyes and benzoates is still unknown. Since cross-reactions to various analgesics and anti-inflammatory drugs such as aspirin, indomethacin, dextropropoxyphene, phenylbutazone, menfenamate, ibu-profen, and sodium salicylate also occur, a nonallergic mechanism seems probable for most patients. A chemical resemblance can clearly be seen only between benzoates and salicylates (Fig. 1). When azo dyes are taken orally there will be an azo-reductive cleavage in the intestinal tract into sulfanilic acid and a pyrazolone derivative which can be further hydrolyzed to sulfophenylhydrazine (Ryan et al. 1969). Some azo dyes can form aniline compounds, which could explain their cross-reactions with preservatives (Walker 1970). 

In the 1960s, in a search for even more effective and less irritating analgesics and anti-inflammatory drugs, the Boots Pure Drug Company in England studied compounds related in structure to salicylic acid. They discovered an even more potent compound, which they named ibuprofen, and soon thereafter, Syntex Corporation in the United States developed... 

Ventafridda, V., Martino, G., Mendelli, V. and ICmanueli, A. (1975) Indoprofen, a new analgesic and anti-inflammatory drug in cancer pain. Clin. Pharmacol. Ther., 17, 284. 

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