Perspective
Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective

https://doi.org/10.1016/j.bcp.2020.114147Get rights and content

Abstract

Owing to the efficacy in reducing pain and inflammation, non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most popularly used medicines confirming their position in the WHO’s Model List of Essential Medicines. With escalating musculoskeletal complications, as evident from 2016 Global Burden of Disease data, NSAID usage is evidently unavoidable. Apart from analgesic, anti-inflammatory and antipyretic efficacies, NSAIDs are further documented to offer protection against diverse critical disorders including cancer and heart attacks. However, data from multiple placebo-controlled trials and meta-analyses studies alarmingly signify the adverse effects of NSAIDs in gastrointestinal, cardiovascular, hepatic, renal, cerebral and pulmonary complications. Although extensive research has elucidated the mechanisms underlying the clinical hazards of NSAIDs, no review has extensively collated the outcomes on various multiorgan toxicities of these drugs together. In this regard, the present review provides a comprehensive insight of the existing knowledge and recent developments on NSAID-induced organ damage. It precisely encompasses the current understanding of structure, classification and mode of action of NSAIDs while reiterating on the emerging instances of NSAID drug repurposing along with pharmacophore modification aimed at safer usage of NSAIDs where toxic effects are tamed without compromising the clinical benefits. The review does not intend to vilify these ‘wonder drugs’; rather provides a careful understanding of their side-effects which would be beneficial in evaluating the risk–benefit threshold while rationally using NSAIDs at safer dose and duration.

Abbreviations

NSAID
Non-steroidal anti-inflammatory drug
PGHS
Prostaglandin-endoperoxide synthase
PG
Prostaglandin
FDA
US Food and Drug Administration
IC
Inhibitory concentration
P450
Cytochromes P450
PLA
Phospholipase
Tx
Thromboxane
LTE
Leukotriene
MOS
Mitochondrial oxidative stress
ETC
Electron transport chain
O2.-
Superoxide
CVD
Cardiovascular disease
TNF-α
Tumor necrosis factor-alpha
NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells
ICAM-1
Intercellular adhesion molecule 1
MAPK
Mitogen activated protein kinase
PKC
Protein kinase C
DRP1
Dynamin-related protein 1
LPS
Lipopolysaccharide
HMGB1
High mobility group box 1
DAMP
Damage associated molecular pattern
MEDAL
Multinational Etoricoxib and Diclofenac Arthritis Long-term trial
GI
Gastrointestinal
MI
Myocardial infarction
HF
Heart failure
VIGOR
Vioxx Gastrointestinal Outcomes Research
APPROVe
Adenomatous Polyp PRevention On Vioxx trial
PRECISION
Prospective Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen
NANSAIDs
Non aspirin NSAIDs
ADMA
Asymmetric dimethyl arginine
eNOS
Endothelial nitric oxide synthase
CKD
Chronic kidney disease
AKI
Acute kidney injury
GFR
Glomerular filtration rate
PPAR
Peroxisome proliferator-activated receptor
CRESCENT
Celecoxib Rofecoxib Efficiency and Safety in Cormorbidities Evaluation Trial
ICH
Intracerebral haemorrhage
AERD
Aspirin-exacerbated respiratory disease
CAP
Community Acquired Pneumonia
Cys-LTEs
Cysteinyl leukotrienes

Keywords

NSAID
Cyclooxygenase
Prostaglandin
Inflammation
Mitochondria
Organ damage
Apoptosis
Gastropathy

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1

Present address: National Institute of Biomedical Genomics, P.O.: N.S.S., Kalyani, West Bengal 741251 India

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