Salicylate anti-inflammatory agents

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... 

Drugs that may affect nateglinide include nonsteroidal anti-inflammatory agents (NSAIDs), salicylates, monoamine oxidase inhibitors, rifamycins, MAOIs, and nonselective beta-adrenergic blocking agents, thiazides, corticosteroids, thyroid products, and sympathomimetics. 

Use with salicylates is not recommended. The use of aspirin with nonsteroidal anti-inflammatory agents (NSAIDs) may cause a decrease in blood levels of the nonaspirin drug. 

Acetyl salicylic acid and related non-steroidal anti-inflammatory agents can cause severe asthma... 

Acute rheumatic fever is treated with anti-inflammatory agents such as aspirin. Corticosteroids are reserved for those patients with severe carditis who do not respond to or are unable to take salicylates. 

Experimental and clinical observations indicate that non-steroidal anti-inflammatory agents (NSAIDs, see p. 403) such as aspirin and indomethacin are effective in controlling diarrhea. This antidiarrheal action is probably due to inhibition of prostaglandin synthesis. Bismuth subsalicylate (pepto-bismol), used for traveler s diarrhea, decreases fluid secretion in the bowel its action may be due to its salicylate component. 

Non-Steroidal Anti-Inflammatory Agents (NASID), like indomethacin and acetyl-salicylic acid (aspirin), induce gastric lesions in man and in experimental animals by inhibition of gastric cyclooxygenase (COX) resulting in less formation of prostacyclin, the predominant prostanoid produced in the gastric mucosa. 

Nonsteroidal anti-inflammatory agents salicylates Indomethacin Clomiphene... 

Researchers at Rutgers University have developed biocompatible polymers that degrade into nonsteroidal anti-inflammatory drugs. For example, the reaction of two equivalents of benzyl salicylate and one equivalent of sebacoyl chloride forms a poly(anhydride ester) called PolyAspirin, which hydrolyzes to salicylic acid (an anti-inflammatory agent) and sebacic acid, which is excreted. This technology can perhaps be used for localized drug delivery at specific sites of injury. What is the structure of PolyAspirin ... 

Yin MJ, Yamamoto Y, Gaynor RB. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 1998 396 77-80. 

Fig. 1 Relationship between amount of drug absorbed though skin and compound octanol-water partition coefficient (increasing lipophilicity). o salicylates other nonsteroidal anti-inflammatory agents. (Redrawn from Ref.. )...

Reizenstein P, Doberl A. Relevance of gastrointestinal symptoms and blood loss after long term treatment with a salicylate-paracetamol ester. A new anti-inflammatory agent (benorylate). Rheum and Rehab Suppl 1973 75. 

Acetylsalicylic add is widely used as an analgesic and anti-inflammatory agent. In the body it is hydrolyzed to salicylate. The assay of salicylate by enzyme electrodes is based on the reaction of salicylate hydroxylase (EC 1.14.13.1) ... 

Reid and his colleagues put forward the theory that the anti-inflammatory action of salicylate is due to its power to form metal chelate complexes. On this basis, it would be predicted that 2,6-dihydroxybenzoic acid (y-resorcylic acid) would be an even more potent anti-inflammatory agent. As already seen (page 77), early hopes of increased potency of this compound were not fulfilled. Nevertheless, the fact remains that many anti-inflammatory substances form coloured complexes with ferric ions in circumstances in which chemically related but inactive compounds do not . Salicylate, phenylbutazone and cinchophen behave in this way. Wiesel described metal chelate compounds of the anti-inflammatory glucocorticoids and showed that... 

To evaluate the time-course of analgesia associated with a non-steroidal anti-inflammatory agent and its copper complex, salicylic acid and its complex were compared in the polyarthritis pain model following oral administration in 5 % gum arabic. Data presented in Figure 6.4 show that analgesic activity increased in a dose-related manner and that Cu(II))(salicylate)2 was 7- to... 

Nivaud-Guemet, E. Guemet, M. Ivanovic, D. Medenica, M. Effect of eluent pH on the ionic and molecular forms of the non-steroidal anti-inflammatory agents in reversed-phase high-performance liquid chromatography. J.Liq.Chromatogr, 1994, 17, 2343-2357 [also aspirin, flufenamic acid, keta-zone, mefenamic acid, niflumic, niflumic acid, nixylic acid, oxyphenbutazone, phenacetin, salicylamide, salicylic acid, sulfinpyrazone]... 

The ionization as anions of many commonly used anti-inflammatory agents is positively correlated with their biological action provided that ionization is not complete and that they are sufficiently lipophilic to reach their prostaglandin-inhibiting site of action. Examples include indomethacin 4.5) and the salicylates (Whitehouse and Dean, 1965). In the phenylindanedione 9.39) series, observation of the effect of varying the (on the anti-inflammatory action) pointed to a need for more accurate determinations of in the or Ao-substituted aryl derivatives, which are by far the most biologically active (van der B vgetaL, 1975). 

Aspirin, an ester of salicylic acid first prepared in 1893, is remarkably versatile. In the body it reduces fever but does not reduce normal body temperature. It also relieves a variety of simple pains such as headache, sprain, and toothache, and is an anti-inflammatory agent often used to treat arthritis. 

Hydrocotyl (Centella asiatica) extract Phenyl salicylate Salicylamide Stearyl glycyrrhetinate anti-inflammatory agent, PMS Vipers bugloss (Echium plantagineum) oil anti-inflammatory agent, respiratory Amylase... 

Having demonstrated an increase in anti-inflammatory activity for the Cu complexes of anthranilic acid and 3,S-dips as well as their safe use it was decided to test the hypothesis that Cu complexes of the clinically used anti-arthritic drugs might be more effective as anti-inflammatory agents than the parent drugs. For this purpose, Cu complexes were prepared using acetylsalicylic acid (aspirin) (12), 2-[3-(trifluoromethyl)phenyl]aminonicotinic acid (niflumic acid, 13) D-penicillamine (D-pen) (14), l-phenyl-5-aminotetrazole (fenamole, 15) and salicylic acid (16). 

Activities of both coordination compounds prepared from fenamole were just as remarkable. The parent compound was inactive at the initial screening dose in the CPE model, active only at the initial screening dose in the CWG model and only active at 4 times the usual initial screening dose in the AA model of inflammation. However, the 2 fenamole Cu complexes were found to be active at low doses in the CPE and CWG models. In the AA model, only one of the 2 complexes was tested but it was found to be active. The 2 Cu salicylate complexes were also found to be potent anti-inflammatory agents in the CPE and CWG models of inflammation. These results are particularly significant in the light of Hangarter s successful therapeutic results with his preparation of Cu salicylate [67,68,71,72]. 

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