Pharmacogenomics of NSAID-Induced Upper Gastrointestinal Toxicity.

L Mcevoy,M Pirmohamed,D F Carr

doi:10.3389/fphar.2021.684162

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are widely used globally for the treatment of pain and inflammation, and in the case of aspirin, for secondary prevention of cardiovascular disease. Chronic non-steroidal anti-inflammatory drug use is associated with potentially serious upper gastrointestinal adverse drug reactions (ADRs) including peptic ulcer disease and gastrointestinal bleeding. A few clinical and genetic predisposing factors have been identified; however, genetic data are contradictory. Further research is needed to identify clinically relevant genetic and non-genetic markers predisposing to NSAID-induced peptic ulceration.

Highlights

non-steroidal antiinflammatory drug (NSAID) comprise a heterogeneous group of non-opioid drugs with effective analgesic, antiinflammatory and antipyretic properties (Calatayud and Esplugues, 2016)
Due to selective COX-2 inhibition, coxibs offer greater GI safety and are associated with a lower risk of upper GI injury and clinically significant ulcer complications compared to traditional NSAIDs (Rostom et al, 2007; Chan et al, 2010)
Several studies have reported no associations between CYP2C9 variants and NSAID-induced peptic ulcer disease (PUD) and/or upper gastrointestinal bleeding (UGIB) (Martin et al, 2001; Van Oijen et al, 2005; Vonkeman et al, 2006; Lopezrodriguez et al, 2008; Ma et al, 2008; Musumba et al, 2013; Ishihara et al, 2014), while others have reported that CYP2C9 variants predispose to PUD (Martínez et al, 2004; Pilotto et al, 2007), including the presence of a gene-dose effect (Figueiras and et al, 2016), and that there may be a combined effect of CYP2C8/CYP2C9 variation (Blanco et al, 2005; Blanco et al, 2008)

Summary

Introduction

NSAIDs comprise a heterogeneous group of non-opioid drugs with effective analgesic, antiinflammatory and antipyretic properties (Calatayud and Esplugues, 2016). Due to selective COX-2 inhibition, coxibs offer greater GI safety and are associated with a lower risk of upper GI injury and clinically significant ulcer complications compared to traditional NSAIDs (tNSAIDs) (Rostom et al, 2007; Chan et al, 2010).

Results

Conclusion