New Pharmacologic Therapies in Gastrointestinal Disease

Wallace, John L.; Ferraz, Jose G.

doi:10.1016/j.gtc.2010.08.020

Cited by 22 publications

(21 citation statements)

References 40 publications

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“…Several approaches have been taken that show promise, mainly using the "codrug" model of drug design [142] . Co-drugs are somewhat like pro-drugs, with the key difference being that the promoiety is not inert; rather, it exerts important pharmacological effects [129] .…”

Section: Novel Intestinal-sparing Nsaidsmentioning

confidence: 99%

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

Wallace¹

2013

WJG

151

148

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This article reviews the latest developments in understanding the pathogenesis, detection and treatment of small intestinal damage and bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs). With improvements in the detection of NSAID-induced damage in the small intestine, it is now clear that this injury and the associated bleeding occurs more frequently than that occurring in the stomach and duodenum, and can also be regarded as more dangerous. However, there are no proven-effective therapies for NSAIDenteropathy, and detection remains a challenge, particularly because of the poor correlation between tissue injury and symptoms. Moreover, recent studies suggest that commonly used drugs for protecting the upper gastrointestinal tract (i.e. , proton pump inhibitors) can significantly worsen NSAID-induced damage in the small intestine. The pathogenesis of NSAIDenteropathy is complex, but studies in animal models are shedding light on the key factors that contribute to ulceration and bleeding, and are providing clues to the development of effective therapies and prevention strategies. Novel NSAIDs that do not cause small in- FRONTIER

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Section: Novel Intestinal-sparing Nsaidsmentioning

confidence: 99%

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

Wallace¹

2013

WJG

151

148

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“…A number of NSAID prodrugs and PPI‐like drugs are in development, aimed at reducing the incidence of NSAID‐induced gastroduodenal injury (see Scarpignato and Hunt 2010 and Wallace and Ferraz, 2010 for recent reviews). Another approach being investigated is the non‐covalent linking of phosphatidylcholine to an NSAID, which in animal studies has been shown to markedly reduce the gastric damaging effects of the NSAID while not impairing the anti‐inflammatory and analgesic effects (Lichtenberger et al ., 2009).…”

Section: Prevention Strategies: Gastroduodenal Injurymentioning

confidence: 99%

NSAID gastropathy and enteropathy: distinct pathogenesis likely necessitates distinct prevention strategies

Wallace

2011

British J Pharmacology

149

158

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The mechanisms underlying the ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to cause ulceration in the stomach and proximal duodenum are well understood, and this injury can largely be prevented through suppression of gastric acid secretion (mainly with proton pump inhibitors). In contrast, the pathogenesis of small intestinal injury induced by NSAIDs is less well understood, involving more complex mechanisms than those in the stomach and proximal duodenum. There is clear evidence for important contributions to NSAID enteropathy of enteric bacteria, bile and enterohepatic recirculation of the NSAID. There is no evidence that suppression of gastric acid secretion will reduce the incidence or severity of NSAID enteropathy. Indeed, clinical data suggest little, if any, benefit. Animal studies suggest a significant exacerbation of NSAID enteropathy when proton pump inhibitors are co-administered with the NSAID. This worsening of damage appears to be linked to changes in the number and types of bacteria in the small intestine during proton pump inhibitor therapy. The distinct mechanisms of NSAID-induced injury in the stomach/proximal duodenum versus the more distal small intestine likely dictate distinct strategies for prevention.

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“…Antioxidant–NSAID hybrids bearing GI protective antioxidant moiety, such as TEMPO or polyphenol may also have therapeutic implications. Combination of naproxen and PPI esomeprazole (Vimovo) was developed by AstraZeneca and several such agents are also being developed . Although this approach could be a useful against NSAID‐induced gastropathy but certainly is not capable to overcome the NSAID‐induced enteropathy.…”

Section: Future Scope Of Developing Nsaidsmentioning

confidence: 99%

Recent Developments in Chimeric NSAIDs as Safer Anti‐Inflammatory Agents

Kumar

Sharma

2014

Medicinal Research Reviews

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NSAIDs are among the most widely prescribed medications across the world, but the gastrointestinal (GI) toxicity still remains the biggest problem and the challenge for current NSAIDs-based therapeutics. The development of selective COX-2 inhibitors was driven by the assumption that selective inhibition of COX-2 would reduce the GI side effects. However, the initial enthusiasm for selective COX-2 inhibitors has faded away due to the emergence of serious side effects associated with the long-term use of these NSAIDs. In the recent years, a number of novel approaches to develop gastrosparing NSAIDs have been explored with the promising results. This review deals with such approaches and strategies that have been employed in the last two decades and are being used currently in the design and development of safer NSAIDs.

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New Pharmacologic Therapies in Gastrointestinal Disease

Cited by 22 publications

References 40 publications

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

Mechanisms, prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

NSAID gastropathy and enteropathy: distinct pathogenesis likely necessitates distinct prevention strategies

Recent Developments in Chimeric NSAIDs as Safer Anti‐Inflammatory Agents

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