Abstract
Nonsteroidal anti-inflammatory drugs (NSAID)s relieve pain, inflammation, and fever by inhibiting the activity of cyclooxygenase isozymes (COX-1 and COX-2). Despite their clinical efficacy, NSAIDs can cause gastrointestinal (GI) and cardiovascular (CV) complications. Moreover, NSAID use is characterized by a remarkable individual variability in the extent of COX isozyme inhibition, therapeutic efficacy, and incidence of adverse effects. The interaction between the gut microbiota and host has emerged as a key player in modulating host physiology, gut microbiota-related disorders, and metabolism of xenobiotics. Indeed, host–gut microbiota dynamic interactions influence NSAID disposition, therapeutic efficacy, and toxicity. The gut microbiota can directly cause chemical modifications of the NSAID or can indirectly influence its absorption or metabolism by regulating host metabolic enzymes or processes, which may have consequences for drug pharmacokinetic and pharmacodynamic properties. NSAID itself can directly impact the composition and function of the gut microbiota or indirectly alter the physiological properties or functions of the host which may, in turn, precipitate in dysbiosis. Thus, the complex interconnectedness between host–gut microbiota and drug may contribute to the variability in NSAID response and ultimately influence the outcome of NSAID therapy. Herein, we review the interplay between host–gut microbiota and NSAID and its consequences for both drug efficacy and toxicity, mainly in the GI tract. In addition, we highlight progress towards microbiota-based intervention to reduce NSAID-induced enteropathy.
Highlights
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs worldwide for the treatment of pain, inflammation, and fever
Based on their selectivity for COX-1 and COX-2 inhibition achieved by therapeutic doses, NSAIDs can be broadly classified into nonselective COX inhibitors, such as aspirin, ibuprofen, indomethacin, and naproxen and selective COX-2 inhibitors, such as diclofenac and coxibs
We report on studies describing how NSAIDs can modify the growth and imbalance the composition of the intestinal microbial communities and the effects of these modifications on the host
Summary
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs worldwide for the treatment of pain, inflammation, and fever. NSAIDs are part of a chemically heterogeneous group of compounds that can be classified on the basis of their relative inhibition of COX isozymes Based on their selectivity for COX-1 and COX-2 inhibition achieved by therapeutic doses, NSAIDs can be broadly classified into nonselective COX inhibitors, such as aspirin, ibuprofen, indomethacin, and naproxen and selective COX-2 inhibitors, such as diclofenac and coxibs (e.g. celecoxib, rofecoxib, etc.). Despite their efficacy in the relief of pain and inflammation, NSAIDs can cause serious adverse events such as gastrointestinal (GI) and cardiovascular (CV) complications in some individuals (Grosser et al, 2017; Bjarnason et al, 2018). Randomized placebo-controlled trials have established that NSAIDs confer a CV hazard in approximately 1 to 2% of people exposed, but the absolute risk may increase with higher drug doses, frequency of use, and established CV disease (Coxib and traditional NSAID Trialists’ (CNT) Collaboration, et al, 2013; Grosser et al, 2017)
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