Aims: 

To review and critically evaluate the current state of gastro-intestinal (GI) reactions to NSAIDs and analgesics.

Methods: 

Literature selected from PubMed and ISI WoK searches with critical assessment.

Results: 

Large scale clinical trials indicate that (1) in the short-term the coxibs have small gains for GI safety, but these are marginal compared with established low ulcerogenic risk NSAIDs (e.g. ibuprofen, etodolac, nabumetone); (2) many reviews have not adequately discriminated co-factors that may be implicated in the development of serious GI adverse reactions (AEs) e.g. stress factors, excess alcohol, concurrent corticosteroids, paracetamol, age and co-infection with Helicobacter pylori; (3) prevention of GI ulcerogenicity, still the only option for preventing damage from NSAIDs, is limited to (a) co-administering anti-secretory agents which may of themselves cause AEs (e.g. Mg⁺⁺ deficiency from PPIs) or lead to digestive complications; b) misoprostol which causes unpleasant diarrhoea and spasms (c) use of opioids (e.g. tramadol) or other pain-relieving therapies of limited benefit or safety, among them a large range of natural products of dubious value or safety. Some components of natural products (e.g. celery seed extract) or metal complexed drugs are cheap alternatives to potent PPIs and antibiotics for treating H. pylori. The development of nitric oxide (NO)-donating NSAIDs has been a disappointment as the claims for lower GI injury and benefits for the CV system. The development of the phospholipid (PL) complexes of NSAIDs pioneered by Lichtenberger and colleagues (e.g. phosphatidyl-choline (PC)-aspirin, PC-ibuprofen and PC-naproxen). The PC component is essentially a surrogate for the PL layer which is a naturally adherent to the GI mucus. The PC-NSAIDs retain all the therapeutic properties of the parent drugs.

Conclusions: 

Although some new NSAIDs and NO-NSAIDs have proven disappointing clinically, some recent innovations in identifying low risk NSAIDs and combining these in gastro-protective formulations may be a way forward for improved therapy with these drugs.