Pharmacogenomics of NSAID-Induced Upper Gastrointestinal Toxicity

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.

A retrospective comparative study of local anesthesia only and local anesthesia with sedation for percutaneous endoscopic lumbar discectomy

“…However, it has several side effects, including nausea, vomiting, dizziness, itching, sedation, respiratory depression, uroschesis, constipation, euphoria, nausea, vomiting, respiratory depression, excessive sedation, and liver dysfunction 32 – 37 . Meanwhile, NSAIDs are predominantly applied to inhibit the synthesis of prostaglandins and the release of bradykinin in the process of inflammation to relieve pain 38 , 39 . Nevertheless, NSAIDs could induce severe gastrointestinal reactions 39 .…”

A Retrospective Comparative Study of Local Anesthesia Only and Local Anesthesia with Sedation for Percutaneous Endoscopic Lumbar Discectomy

“…However, it has several side effects, including nausea, vomiting, dizziness, itching, sedation, respiratory depression, uroschesis, constipation, euphoria, nausea, vomiting, respiratory depression, excessive sedation, and liver dysfunction [31][32][33][34][35][36] . Meanwhile, NSAIDs are predominantly applied to inhibit the synthesis of prostaglandins and the release of bradykinin in the process of in ammation to achieve pain relief 37,38 . Nevertheless, NSAIDs occasionally lead to severe gastrointestinal reactions 38 .…”

Pharmacogenetics in Primary Headache Disorders

“…The analgesic and anti-inflammatory properties of NSAIDs lead to a wide use for the relief of acute migraine attacks and TTHs ( Pavithra et al, 2020 ; Pardutz and Schoenen, 2010 ; National Clinical Guideline Centre (UK), 2012 ). The main mechanism of their action is the inhibition of the enzymes COX-1 and/or COX-2, which are responsible for the synthesis of prostaglandins that are involved in the inflammatory cascade and in hyperalgesia ( Blanco et al, 2008 ; McEvoy et al, 2021 ). Adverse effects induced by nonselective NSAIDs are caused by the inhibition of constitutionally expressed COX-1 found in different tissues.…”

“…Genetic polymorphisms of the mentioned phase one genes, i.e., CYP2C8*3 and CYP2C9 2* and *3 , are responsible for the reduced activity of the enzymes, which potentially lead to higher plasma levels of NSAIDs and, thus, stronger adverse effects of these drugs ( Dorado et al, 2008 ; Figueiras et al, 2016 ; Zajic et al, 2019 ; Blanco et al, 2008 ). The mentioned genetic variants have been associated with an increased risk of adverse effects, including hepatotoxicity and gastrointestinal bleeding ( Figueiras et al, 2016 ; Zajic et al, 2019 ; Blanco et al, 2008 ; McEvoy et al, 2021 ) ( Table 3 ). Genetic polymorphisms in the genes coding for UDP-glucuronosyltransferases that are responsible for the conjugation of NSAID metabolites may also be associated with impaired clearance of NSAIDs.…”