Antirheumatics groups

From the various modifications that have been made on the phenylbutazone structure in order to increase activity and reduce toxicity it has been found that the activity persists when methyl, chloro, hydroxy or nitro groups are introduced into the para position of one or both benzene rings (see oxyphenbutazone (712) as an example). Mofebutazone (714) has also been used in Europe for several years as an antirheumatic drug. 

Salicylic acid is manufactured on a large scale. In the dye industry it serves for the production of valuable azo-dyes which exhibit great fastness. To some extent these dyes are applied to mordanted fibres. In addition, the acid and its derivatives are widely used in pharmacy. Being a phenolcarboxylic acid it has a powerful disinfecting action (preservative). It has further proved itself an important antirheumatic and an analgetic. The derivative in which the phenolic hydroxyl group is acetylated (aspirin) has become especially popular. The first medicament of the series was the phenyl ester of salicylic acid, salol, which is produced as a by-product in the technical process. The preparation of salicylaldehyde has been described above (p. 235). 

To increase the stability of potentially antirheumatic pyran 143 toward acids, two analogs, bearing 2-N-pyrrolo- 276 and 2-succinimido 277 groups, were prepared by conventional methods (95BML2783) (Scheme 112). 

Another important group of agents is characterized as disease-modifying antirheumatic drugs (DMARDs). They decrease inflammation, usually improve symptoms, and slow the bone damage associated with rheumatoid arthritis. They are thought to affect more basic inflammatory mechanisms than do glucocorticoids or the NSAIDs. They may also be more toxic than those alternative medications. 

Benefits Significant antirheumatic and antiaithritic actions have been demonstrated in several studies, some with large groups of participants. Diuretic properties have been reported in connection with prostate problems and in cases of lower urinary tract infections. 

The role of the antipyretic activity of these compounds is even less clear, but it is significant that all the known clinically effective antirheumatic drugs of this group are also antipyretics, and this property may be of fundamental importance . In this context, it is of interest to note that ethyl a-(4-phenylphenoxy) propionate, an anti-inflammatory compound which does not exhibit antirheumatic activity possesses only very weak antipyretic properties. ... 

Allergic contact dermatitis is one of the commonest allergic skin diseases caused by drugs. The main causes are attributed to the group of antibiotics, chemothera-peutics, local analgetics, antirheumatics, antimycotics, disinfectants, antihistamin-ics, as well as ingredients of the vehicles (preservatives, antioxidants, and others). Further details will be found elsewhere in this book (Chap. 13). 

The utter neglect of this potent drug in modern medical practice has been mainly due to its toxicity and vesicent action on external application or internal administration. Studies in its chemical constitution have to some extent made it possible to control its toxicity. Thus it was found that the free hydroxyl groups and the two double bonds in the side chain of bhilawanol are together responsible for its vesicent action. When both these active centres are eliminated as for instance in diacetyl or dimethyl-tetrahydro-bhilawanol, a completely non-vesicent product results. Unfortunately, studies in the correlation of structure and activity in respect of its antirheumatic and a wide range, of other therapeutic properties claimed for it have not so far been undertaken. 

The broadest clinical experience with SACC therapy was gained in the treatment of RA. Of the original group of 27 patients 13 (48%) progressed to a symptom free classification, 13 (48%) progressed to the improved " classification, and only 1 patient was unaffected by SACC therapy. Many of these patients had been previously ineffectually treated with a variety of antirheumatic drugs, including salicylates, Au compounds and corticoids but they responded to SACC in a step-by-step fashion. 

The selected compounds studied were the corticoids, betamethasone, and derivatives. Corticoids are a group of drugs with therapeutic action as antiinflammatory, antialergic, and antirheumatic properties. Betamethasone and synthetic derivatives have similar chemical structures (Figure 19.4). Esterification in position 17 and/or 21 leads to compounds with different hydrophobicity and they have been used in different pharmaceutical administrations, log kf for betamethasone and derivatives have been determined in those MEEKC systems and the Equation 19.10 applied for calculation of log P. The measured mobilities and retention factors of the analytes in different MEEKC systems are shown in Table 19.3. 

---