NSAIDs: eNdocannabinoid stimulating anti-inflammatory drugs?
ABSTRACT Read any pharmacology textbook and the message is clear: nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting the activity of cyclooxygenase (COX) and thereby the production of prostaglandins. However, evidence is accumulating that NSAIDs involve the endocannabinoid system in their actions, and that such effects may pave the way towards the design of new analgesics that are not plagued with the gastrointestinal and cardiovascular adverse actions that are associated with this class of drugs. In this Opinion article, our current understanding of the involvement of the endocannabinoid system in the actions of NSAIDs is described, and the ways in which this can lead to novel drug development is discussed.
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ABSTRACT: This article aims to review osteoarthritis of the hand and the role of the non-steroidal anti-inflammatory drug (NSAID) naproxen on its management. We discuss the chemical and pharmacological properties of naproxen and the NSAID class, with an emphasis on its mechanism and adverse reactions. In the context of part I of this paper in characterizing hand osteoarthritis (OA), we review clinical trials that have been conducted involving hand OA and naproxen. The therapeutic effect of NSAIDs stems from its role on inhibiting cyclo-oxygenase (COX)-1 or COX-2 enzyme activity in the body. These enzymes play a major role in maintaining several functions in the body and due NSAIDs' inhibitory effects; many principle adverse reactions occur with the use of NSAIDs such as: gastrointestinal tract issues, cardiovascular risks, renal, hepatic, central nervous system and cutaneous. Review of clinical trials involving naproxen and hand OA show that it is significantly more efficacious when compared with placebo. These studies, along with the finding that naproxen is of least cardiovascular risk in the NSAID class, may show that it can be part of one of the approaches in managing the condition. It is important to note that the optimal NSAID to use varies for each individual. The finding that the use of naproxen leads to the smallest increase in cardiovascular risk appeals to those at-risk individuals who suffer from OA and require pharmacological treatment for relief.The Journal of pharmacy and pharmacology. 10/2013;
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ABSTRACT: The endocannabinoid system consists of cannabinoid CB1 and CB2 receptors, of endogenous agonists for these receptors known as 'endocannabinoids', and of processes responsible for endocannabinoid biosynthesis, cellular uptake and metabolism. There is strong evidence first, that this system up-regulates in certain disorders as indicated by an increased release of endocannabinoids onto their receptors and/or by increases in the expression levels or coupling efficiency of these receptors, and second, that this up-regulation often appears to reduce or abolish unwanted effects of these disorders or to slow their progression. This discovery has raised the possibility of developing a medicine that enhances up-regulation of the endocannabinoid system associated with these disorders by inhibiting the cellular uptake or intracellular metabolism of an endocannabinoid following its 'autoprotective' endogenous release. For inhibition of endocannabinoid metabolism, research has focused particularly on two highly investigated endocannabinoids, anandamide and 2-arachidonoyl glycerol, and hence on inhibitors of the main anandamide-metabolising enzyme, fatty acid amide hydrolase (FAAH), and of the main 2-arachidonoyl glycerol-metabolising enzyme, monoacylglycerol (MAG) lipase. The resulting data have provided strong preclinical evidence that selective FAAH and MAG lipase inhibitors would ameliorate the unwanted effects of several disorders, when administered alone or with a cyclooxygenase inhibitor, and that the benefit-to-risk ratio of a FAAH inhibitor would exceed that of a MAG lipase inhibitor or dual inhibitor of FAAH and MAG lipase. Promising preclinical data have also been obtained with inhibitors of endocannabinoid cellular uptake. There is now an urgent need for clinical research with these enzyme and uptake inhibitors.Proceedings of The Nutrition Society 10/2013; · 3.67 Impact Factor