Nonsteroidal anti-inflammatory drugs selective

Nonsteroidal anti-inflammatory drugs (NSAIDs) may be initiated if acetaminophen therapy fails. At equipotent doses, all NSAIDs elicit similar analgesic and anti-inflammatory responses. Selection is based on patient preference, dosing frequency, tolerability, and cost. 

Nonsteroidal anti-inflammatory drugs, colchicine, or corticosteroids are used for acute attacks. Selection depends on several patient factors, especially renal function. 

Rifaximin Rifamycin Antibiotic Gut bacteria Enteric infection Diarrhea, infectious Hepatic encephalopathy Small intestine bacterial overgrowth Inflammatory bowel disease Colonic diverticular disease Irritable bowel syndrome Constipation Clostridium difficile infection Helicobacter pylori infection Colorectal surgery Bowel decontamination, selective Pancreatitis, acute Bacterial peritonitis, spontaneous Nonsteroidal anti-inflammatory drug enteropathy... 

SSRI = Selective serotonin reuptake inhibitor NSAID = Nonsteroidal anti-inflammatory drug CYP = cytochrome P-450 NAT2 = N-acetyl transferase type 2 J = Japanese C = Chinese A = African American. Poor metabolizers are not always at increased risk of ADR. 

Mobic is the proprietary preparation of meloxicam, a non-steroidal antiinflammatory drug, which is also a selective inhibitor of cyclo-oxygenase-2. It is therefore less likely to cause gastrointestinal side-effects than other nonsteroidal anti-inflammatory drugs. However, it is still best to administer meloxicam after food. 

There is intriguing evidence that shows that nonsteroidal anti-inflammatory drugs have anticancer activity that could potentially lead to the use of these drugs or the newer generation of selective cox-2 inhibitors for their anticancer activity. Chapter 22 by Pyo et al. will expand upon this and address the impact of the interesting observation that a combination of the selective cox-2 inhibitor, SC-236, and radiation was found to cause a dose enhancement factor of at least 1.4 at a surviving fraction of 0.1 (71). 

Elder DJE, HaltonDE, Hague A, etal. Induction of apoptotic cell death in human colorectal carcinoma cell lines by a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug independence from COX-2 protein expression. Clin Cancer Res 1997 3 1679-1683. 

COX-1 and COX-2 are the targets of the nonsteroidal anti-inflammatory drugs (NSAID, see Chapter 28). Indirectely the effect of these enzymes is also inhibited by corticosteroids (see also Chapter 26) through a decrease of the availibility of its substrate arachidonic acid by inhibition of phospholipase A2. Relatively new drugs, known as COX-2 selective inhibitors or coxibs (celecoxib, rofecoxib and others), are used as specific inhibitors of COX-2. 

Many nonsteroidal anti-inflammatory drugs of different chemical structures (Fig. 5) have been introduced for the treatment of inflammatory and painful conditions. Many years of clinical experience with these drugs have shown that there is no induction of tolerance or dependence and no respiratory depression as seen with opioids. The major side-effects of these compounds with COX-1 selectivity or balanced COX-1 and COX-2 inhibition are damage to the gastric mucosa, prolongation of bleeding time and renal failure. 

Cryer, B., Feldman, M. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am. J. Med. 1998, 104, 413-421. 

On the other hand, reduction of a,p-unsaturated compounds under the same conditions leads to the corresponding saturated ketones. This result can be reached in two cases of industrial interest such as the reduction of P-ionone into dihydro-P-ionone (entry 3), a valuable intermediate for the flavors and fragrances industry, and the reduction of 4-(6-methoxy-2-naphthyl)-3-buten-2-one into nabumetone (entry 4), a nonsteroidal anti-inflammatory drug [33], The selective hydrogenation of P-ionone can be performed in 89% yield using Raney nickel alloy treated with sodium hydroxide [34], with a Ru-C catalyst [35] or with Ph3SnH [36]. On the other hand Pd/C [37, 38] and Rh(T0A)/Al203 systems [39] are reported to be selective for the preparation of nabumetone. 

Nonsteroidal anti-inflammatory drugs (NSAlDs) nonselectively inhibit the activities of both COX-1 and COX-2. Out of concern for the gastrointestinal side effects of NSAID, scientists have discovered and developed many specific COX-2 inhibitors that facilitate a safer choice for controlling inflammatory diseases (73). Eor example, NS-398, a selective COX-2 inhibitor, has been shown to reduce tension (mechanical stress)-induced PGE2 production from periodontal ligament cell cultures (74). 

Spilding WM, Reeves MJ, Whelton A. Thromboembolic Cardiovascular Risk Among Arthritis Patients Using Cyclooxygenase-2-Selective Inhibitor or Nonselective Cyclooxygenase Inhibitor Nonsteroidal Anti-inflammatory Drugs. American Journal of... 

Mitchell J A, Akeirasereenont R Thiemermann C et al 1993 Selectivity of nonsteroidal anti-inflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proceedings of the National Academy of Sciences of the USA 90 11693-11697... 

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