Nonsteroidal anti-inflammatory drugs injury

A. Muhlberg, C. Linz, E. Bern, L. Tucker, M. Ver-have, and R. Grand, Identifaction of nonsteroidal anti-inflammatory drug induced gastrointestinal injury in children with juvenile rheumatoid arthritis, J. Pediatr, 122, 647 (1993). 

In addition to their beneficial effects, some medications may actually cause cellular injury and disease. An example of this phenomenon involves nonsteroidal anti-inflammatory drugs (NSAIDS). These drugs include aspirin (a derivative of salicylic acid), ibuprofen (arylpropionic acid, Advil ), and acetaminophen (para-aminophenol derivative, Tylenol ). Because of their beneficial pharmacological effects, consumption of these agents has increased significantly in recent years. NSAIDS have the ability to treat fever, pain, acute inflammation, and chronic inflammatory diseases such as arthritis. They are also used prophylactically to prevent heart disease, stroke, and colon cancer. 

Dozens of combination products are available only a few of the most commonly prescribed are listed here. Codeine combination products available in several strengths are usually denoted No. 2 (15 mg codeine), No. 3 (30 mg codeine), and No. 4 (60 mg codeine). Prescribers should be aware of the possible danger of renal and hepatic injury with acetaminophen, aspirin, and nonsteroidal anti-inflammatory drugs contained in these analgesic combinations. 

Morini, G., Grandi, D., Krause, M., Schunack, W., 1997. Gastric mucosal injury by nonsteroidal anti-inflammatory drugs is reduced by (R)-a-methylhistamine and its prodrugs in the rat. Inflamm. Res. 46 (Suppl. 1), S101-S102. 

Perini R, Fiorucci S, Wallace JL. Mechanisms of nonsteroidal anti-inflammatory drug-induced gastrointestinal injury and repair a window of opportunity for cyclooxygenase-inhibiting nitric oxide donors. Can J Gastroenterol. 2004 18 229-236. 

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 ... 

Loeb DS, Talley NJ, Ahlquist DA, Carpenter HA, Zinsmeister AR. Long-term nonsteroidal anti-inflammatory drug use and gastroduodenal injury the role oi Helicobacter pylori. Gastroenterology 1992 102(6) 1899-905. 

Garcia Rodriguez LA, Williams R, Derby LE, Dean AD, Jick H. Acute liver injury associated with nonsteroidal anti-inflammatory drugs and the role of risk factors. Arch Intern Med 1994 154(3) 311-16. 

Laine L. Review article The effect of Helicobacter pylori iirfection on nonsteroidal anti-inflammatory drug-induced upper gastrointestinal tract injury. Aliment Phamacol Ther 2002 16(Suppl l) 34-39. 

Inhibition of COX that leads to less proinflammatory PG production at the injury site is the major mechanism of action of nonsteroidal anti-inflammatory drugs (NSAID) (4). Molecular cloning studies have identified two forms of COX (5,6), COX-1, a constitutive form responsible for housekeeping functions, and COX-2, an inducible form that mediates many of the inflammatory and inducible effects. Both forms carry out essentially the same catalytic reaction and have similar primary sequences (5,6). Selective inhibitors of the inducible COX-2 would therefore be ideal as NSAID that are free of side effects (7). 

GI Injury and Ulcer Models Acute or chronic GI injury models are induced by various compounds or agents in rodents. Intragas trie administrations of concentrated ethanol (50-100%), sodium hydroxide (NaOH), acetic acid, and hydrochloric acid (HCl) have been shown to induce mucosal injury in fasted rats. Of these models, ethanol and HCL models are relevant to humans, mimicking alcohol consumption and overproduction of HCL in the stomach. GI ulcer models include administration of nonsteroidal anti-inflammatory drugs (NSAIDs) such as... 

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