Background: 

NSAIDs and analgesics are the mainstay of pain control for patients with arthritic, musculoskeletal conditions as well as acute pain. Their use is controversial since they are the cause of iatrogenic diseases (e.g. gastrointestinal bleeding, renal, hepatic, cutaneous conditions). Since the withdrawal of rofecoxib due to cardiovascular (CV) events and consequent enquiries into the CV safety of all NSAIDs, there have been extensive studies undertaken on the clinical and epidemiological adverse reactions. There have also been concerns about the hepatic safety with paracetamol.

Current Issues: 

There are several over-riding features about the associations of serious adverse reactions (AEs) from the NSAIDs and paracetamol: (a) many of the studies have not adequately discriminated the roles of socio-psychologic or physical stressors as co-factors in the development of serious AEs; (b) the elderly are at particular risk yet little is known about the impairment of mucosal defences or roles of pharmacokinetics; (c) in many situations there are overlapping reactions arising from one organ system that affect others. Among these is the co-infection with Helicobacter pylori, which not only contributes to peptic ulcer disease but can as a result of systemic immuno-inflammatory reactions. Absorption of pathogenic antigens from this organism can lead to inflammatory conditions in other organs (e.g. the CV, hepatic systems). Thus, there may be complex inter-relationships between AEs in the GI tract with those in CV and hepato-renal systems, which can be driven by the systemic immune reactions from Th1, Th17 cells driving reactions which are either activated or driven by NSAIDs. Other common pathogens (e.g. chlamydia, E. coli) may also contribute to systemic inflammatory reactions which exacerbate GI, CV, hepato-renal AEs attributed to NSAIDs.

Conclusions: 

gastric H. pylori and other GI pathogens have profound systemic consequences in organs outside the GI tract leading to immuno-inflammatory reactions that may contribute to serious CV and hepato-renal reactions.