Side Effects Of Nonsteroidal Anti-inflammatory Drugs Research Articles

Oral Aloe vera as a treatment for osteoarthritis: a summary

While pain relief is a basic tenet of health care, pain is under-treated in the UK (Davies and Mcvicar, 2000) and this issue remains unresolved. This paper suggests that oral Aloe vera could be used in the treatment of chronic non-cancer pain (CNCP), particularly that caused by osteoarthritis (OA). Despite being used as arthritis treatment for centuries (Yoo et al, 2008), evidence of effectiveness of Aloe vera is anecdotal or from small studies. The perceived benefits of prescribing Aloe vera for OA may be twofold: it has utility as an anti-inflammatory agent and also as a prophylactic against the gastrointestinal irritant effects of non-steroidal anti-inflammatory drugs (NSAIDs). Long-term, randomized, controlled studies are still needed to address the lack of evidence informing optimum prescribing of pain medication for people with OA (Cowan, 2007). There is no reason that so called 'nutraceutical' agents should not be subjected to the same rigorous randomized, controlled, double-blind trials as other 'mainstream' drugs. Therefore, it is appropriate to ask whether NSAID treatment and side effects can be improved by the addition of oral Aloe vera. Thus, we may then be in a more informed position to resolve the ongoing 'Pandemonium over Painkillers' (Cowan, 2007).

Athletes, NSAID, Coxibs, and the Gastrointestinal Tract

The role of nonsteroidal antiinflammatory drugs (NSAID) in pain and inflammation has been evaluated in many forms over the last decade. Emerging evidence shows that this class of medications has different effects depending on injury type: bone, ligament, tendon, and muscle. There are no clear guidelines about specific NSAID choice, duration of use, or route of administration. Benefit of therapy must be weighed against the side effects of NSAID, specifically with respect to the gastrointestinal and renal systems. It is clear that the side effect profile changes within the subclasses of NSAID, nonspecific cyclo-oxygenase-1 and 2 (COX-1 and COX-2) inhibitors, and more selective COX-2 inhibitors. Safe and effective alternatives may include topical NSAID and acetaminophen.

Scientific Opinion on the substantiation of health claims related to gamma linolenic acid and maintenance of joints (ID 494, 637, 1774, 2098), weight maintenance following weight loss (ID 496), maintenance of peripheral blood flow (ID 638), maintenance of normal blood pressure (ID 1771), maintenance of normal blood cholesterol concentrations (ID 1771) and maintenance of bone (ID 1774) pursuant to Article

Scientific Opinion on the substantiation of health claims related to gamma linolenic acid and maintenance of joints (ID 494, 637, 1774, 2098), weight maintenance following weight loss (ID 496), maintenance of peripheral blood flow (ID 638), maintenance of normal blood pressure (ID 1771), maintenance of normal blood cholesterol concentrations (ID 1771) and maintenance of bone (ID 1774) pursuant to Article

Are Patients Aware of Upper Gastrointestinal (GI) Side Effects of Nonsteroidal Anti-inflammatory Drugs (NSAIDs)? An Inner City Community Hospital Experience

Purpose: NSAID associated GI side effects are a significant cause of morbidity and mortality. Although much is known about NSAIDs and their GI side effects, little is known about patient awareness of NSAID related upper GI side effects in the United States. The aim of our study was to evaluate patient awareness about NSAID induced upper GI side effects. Methods: A retrospective analysis utilizing a standard questionnaire completed during physician encounter at Interfaith Medical Center, Brooklyn NY from March to May 2009. All patients 18 years of age or older currently taking NSAID or having used NSAID in the last 2 years were included in the study. Those who never used NSAID and critical care patients were excluded. The questionnaire included demographics, co-morbidities, indication and duration of NSAID use and awareness of upper GI side effects. Complications of NSAID such as heartburn, abdominal pain, ulcer, bleeding and perforation were evaluated. There were 130 females and 180 males included in the study. The data was analyzed using regression analysis, t-test, correlation and Chi-square test as indicated. Results: The ages ranged from 18-93 years with mean age of 52 years. African-Americans comprised 88.7% of the study population. Only 15.8% patient had achieved education beyond high school. Motrin was the most commonly used NSAID (41.6%) and 37.7% patients had used two or more types of NSAIDs at different times. 68% of patients were not aware of any upper GI side effects while 32% were aware of some side effects. Of those who were aware of some side effects, only 44% patients knew NSAIDs could cause peptic ulcers and upper GI bleeding. About 50% of patients who were prescribed NSAID claimed that they were not counseled of potential GI side effects. Patients who had used 2 or more types of NSAID were more aware of side effects compared to those taking less than 2 types (p: 0.016). Among those patients who had used multiple NSAIDs, only 30% had been made aware of upper GI side effects (p: 0.009). 37% of patients who claimed they read side effects profile of NSAID were aware of some side effects compared to 14% of those who never read side effects profile (p: 0.04). Only 5 out of 26 patients with PUD were aware of side effects (p: 0.02). There was no statistically significant difference in awareness in terms of education, duration, indications and between patients who were prescribed vs. those who took OTC. Conclusion: Despite the associated significant mortality and morbidity and high cost of treatment, most patients remain unaware of upper GI side effects of NSAID. We can hope that increased patient knowledge of side effects may reduce the incidence and prevalence of GI complications due to these medications.Table

Use of NSAIDs in triathletes: prevalence, level of awareness and reasons for use

ObjectiveTo determine the level of awareness regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and the prevalence and reasons for their consumption among athletes competing at the 2008 Brazil Ironman Triathlon (3.8 km...

A Role for HSP70 in Protecting against Indomethacin-induced Gastric Lesions

A major clinical problem encountered with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, is gastrointestinal complications. Both NSAID-dependent cyclooxygenase inhibition and gastric mucosal apoptosis are involved in NSAID-produced gastric lesions, and this apoptosis is mediated by the endoplasmic reticulum stress response and resulting activation of Bax. Heat shock proteins (HSPs) have been suggested to protect gastric mucosa from NSAID-induced lesions; here we have tested this idea genetically. The severity of gastric lesions produced by indomethacin was worse in mice lacking heat shock factor 1 (HSF1), a transcription factor for hsp genes, than in control mice. Indomethacin administration up-regulated the expression of gastric mucosal HSP70. Indomethacin-induced gastric lesions were ameliorated in transgenic mice expressing HSP70. After indomethacin administration, fewer apoptotic cells were observed in the gastric mucosa of transgenic mice expressing HSP70 than in wild-type mice, whereas the gastric levels of prostaglandin E(2) for the two were indistinguishable. This suggests that expression of HSP70 ameliorates indomethacin-induced gastric lesions by affecting mucosal apoptosis. Suppression of HSP70 expression in vitro stimulated indomethacin-induced apoptosis and activation of Bax but not the endoplasmic reticulum stress response. Geranylgeranylacetone induced HSP70 at gastric mucosa in an HSF1-dependent manner and suppressed the formation of indomethacin-induced gastric lesions in wild-type mice but not in HSF1-null mice. The results of this study provide direct genetic evidence that expression of HSP70 confers gastric protection against indomethacin-induced lesions by inhibiting the activation of Bax. The HSP inducing activity of geranylgeranylacetone seems to contribute to its gastroprotective activity against indomethacin.

Prostanoids in health and disease

The prostanoids are a family of lipid mediators generated by the action of cyclooxygenase on a 20-carbon unsaturated fatty acid, arachidonic acid. Prostanoids are generated widely in response to diverse stimuli and, acting in a paracrine or autocrine manner, play important roles in normal physiology and disease. This review summarizes the current knowledge on prostanoid generation and the roles of individual mediators, their biosynthetic pathways, and their receptors in health and disease.

Cyclooxygenase-2 inhibitors in patients with high gastrointestinal risk: are we there yet?

Gastrointestinal complications from the use of nonsteroidal antiinflammatory drugs (NSAIDs) are common and costly. Cyclooxygenase (COX)-2 inhibitors cause fewer gastrointestinal events than nonselective NSAIDs but may still result in peptic ulcer complications in a significant proportion of high-risk patients. The risk can be further reduced by prescribing COX-2 inhibitors together with proton pump inhibitors. Small-bowel injury is also commonly seen in long-term users of COX-2 inhibitors. The potential cardiovascular side effects of most COX-2 inhibitors and NSAIDs pose great challenge to physicians. Further studies are required to optimize the treatment regimen in patients with high cardiovascular and gastrointestinal risk and to decide the best treatment options for patients with small- and large-bowel complications.

Association of phosphatidylcholine and nsaids as a novel strategy to reduce gastrointestinal toxixity

Nonsteroidal anti-inflammatory drugs (NSAIDs) are highly effective drugs that inhibit pain and inflammation, and perhaps due to the role of inflammation in the underlying etiology, NSAIDs have also demonstrated efficacy in reducing a patient's risk of developing a number of cancers and neurological diseases (e.g. Alzheimer's disease). The utility of these powerful drugs is limited due to their gastrointestinal (GI) side-effects, notably peptic ulceration and GI bleeding which is briefly reviewed here. We also describe the barrier property of the GI mucosa and how it is affected by NSAIDs, as it is our position that disruption of the surface barrier is an important component in the drugs' pathogenesis, in addition to selective inhibition of COX-2, which has proven to be problematic. We also discuss current alternative approaches being taken to mitigate the GI side-effects of NSAIDs, including developing combination drugs where NSAIDs are packaged with inhibitors of HCl secretion such as proton pump inhibitors or H2-receptor antagonists. We then present the rationale for the development of the PC associated NSAID technology which came out of our observation that the mammalian gastric mucosa has hydrophobic, nonwettable properties that provides a barrier to luminal acid, and the role of phospholipids and specifically phosphatidylcholine (PC) in this barrier property. In the last section we review the development of our current lipid-based PC-NSAID formulations and our encouraging preclinical and clinical observations validating their GI safety and therapeutic efficacy.

Non-opioid analgesics: prescribing rationale and uses

This article provides an overview of non-opioid analgesics. There is a consideration of the mechanisms of action of paracetamol, aspirin and the nonsteroidal anti-inflammatory drugs (NSAIDs). The contraindications, cautions and side-effects of NSAIDs are summarized in a series of tables. There is a discussion of some of the common prescribing issues that relate to this group of analgesics. The reader has the opportunity to self-check their own knowledge with a pre-reading self-assessment.

Pemberian Obat-Obatan Anti Inflamasi Non Steroid (AINS) pada Anak

We know that non-steroid anti-inflammatory drugs (NSAIDs) analgetic, antipirettan and anti-inflammatory effect. This drugs can decrease pain simptomaticly, the most widely prescribed drugs worldwide and being the drugs of first choice other inflammatory pain. There is many kind NSAIDs that we knaw, like aspirin, parasetamol, ibuprofen, mefenamic acid, endometasin, diklofenak, piroksikan and nemosulide. Every kind of NSAIDs has its advantage and dis advantage for that beneficial actions and side effects. That beneficial actions and harmful side effects of NSAID can be associated with its mechanism of action. Using NSAID for children must in attention. This article is expented to give information and to help the collegnes in the selecting drugs NSAID for child. DOI: 10.14693/jdi.v15i3.27

Penggunaan obat anti-inflamasi nonsteroid pada anak

We know that non-steroid anti-inflammatory drugs (NSAID) have analgetic, antipirettanand anti-inflammatory effect. This drugs can decrease pain simptomaticly, the most widelyprescribed drugs worldwide and being the drugs of first choice other inflammatory pain.There is many kind NSAID that we knaw, like aspirin, parasetamol, ibuprofen, mefenamicacid, endometasin, diklofenak, piroksikan and nemosulide. Every kind of NSAID has itsadvantage and dis advantage for that beneficial actions and side effects. That beneficialactions and harmful side effects of NSAID can be associated with its mechanism of action.Using NSAID for children must in attention. This article is expented to give informationand to help the collegnes in the selecting drugs NSAID for child.

Carbonic Anhydrase Inhibition: Insight into Non-COX-2 Pharmacological Effect of some Coxibs

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent the most commonly used medications for the treatment of pain and inflammation, but numerous well-described adverse drug reactions (ADRs) limit their use. These drugs act via the inhibition of cyclooxygenase (COX) enzyme of which at least two isoforms were described: COX-1 which plays important roles in homeostatic processes such as thrombogenesis and homeostasis of the gastrointestinal tract and kidneys and COX-2 expressed in pathological conditions such as inflammation or cancer proliferation. Selective COX-2 inhibitors or "coxibs" were initially developed as a therapeutic strategy to avoid not only the gastrointestinal but also the renal and cardiovascular side effects of non specific NSAIDs. However, this class of drug did not fulfill all their promises. Indeed, numerous unexpected side effects have limited their use and some of them have been withdrawn or suspended from the market for different safety reasons including cardiovascular, hepatic and skin adverse reactions. For instance, cardiovascular warnings have been applied to the whole class of coxibs and more recently for all classical NSAIDs as well. However, differences in the chemical structures should be taken into consideration in order to discriminate between coxibs and the development of some ADRs of which renal events and hypertension. The aim of this paper is to focus on the differences in chemical structures of all marketed COX-2 inhibitors and their unexpected effects on carbonic anhydrase in order to provide non-COX-2 mechanistic insights into some of the differences observed between coxibs.

Nimesulide is a Selective COX-2 Inhibitory, Atypical Non-Steroidal Anti-Inflammatory Drug

In this review it is shown that nimesulide, a selective cyclooxigenase-2 (COX-2) inhibitor, is different from other selective COX-2 inhibitors and classical non-steroidal anti-inflammatory drugs (NSAIDs). The anti-inflammatory effect mechanism of nimesulide (inhibition of inflammatory mediators) is similar to other classic NSAIDs, but the protective effect of nimesulide on classic NSAID-induced ulcers elucidates the difference between nimesulide and these other drugs. It is known that the selective COX-2 inhibitor nimesulide prevents NSAID-induced ulcers, while celecoxib and rofecoxib, which are more selective to COX-2, failed to prevent these ulcers. Nimesulide produces gastro-protective effects via a completely different mechanism. In addition, while selective COX-2 inhibitors increase the risk for cardiovascular diseases, nimesulide does not exert significant cardiotoxicity. This data suggests that gastrointestinal side effects of classic NSAIDs cannot be related to the COX-1 inhibition alone and also suggest that nimesulide is an atypical NSAID, which is different from both non-selective and selective COX-2 inhibitors.

Nitric oxide and cardiovascular effects: new insights in the role of nitric oxide for the management of osteoarthritis

Nitric oxide (NO) is an important mediator in both health and disease. In addition to its effects on vascular tone and platelet function, it plays roles in inflammation and pain perception that may be of relevance in osteoarthritis. Many patients with osteoarthritis take nonsteroidal anti-inflammatory drugs (NSAIDs) long term for pain control. Over recent years concern has been raised about the possible cardiovascular side effects of NSAIDs. The reasons for this possible increased cardiovascular risk with NSAIDs are not yet entirely clear, although changes in blood pressure, renal salt handling and platelet function may contribute. Recently, drugs that chemically link a NSAID with a NO donating moiety (cyclo-oxygenase-inhibiting NO-donating drugs [CINODs]) were developed. NO is an important mediator of endothelial function, acting as a vasodilator and an inhibitor of platelet aggregation, and having anti-inflammatory properties. The potential benefits of CINODs include the combination of effective analgesic and anti-inflammatory actions with NO release, which might counterbalance any adverse cardiovascular effects of NSAIDs. Effects of CINODs in animal studies include inhibition of vasopressor responses, blood pressure reduction in hypertensive rats and inhibition of platelet aggregation. CINODs may also reduce ischemic damage to compromised myocardial tissue. In addition, endothelial dysfunction is a recognized feature of inflammatory arthritides, and therefore a drug that might provide slow release of NO to the vasculature while treating pain is an attractive prospect in these conditions. Further studies of the effects of CINODs in humans are required, but these agents represent a potential exciting advance in the management of osteoarthritis.

Development of new type of NSAIDs with lower gastric side effects

Non-steroidal anti-inflammatory drugs (NSAIDs) are a useful family of therapeutics. The anti-inflammatory actions of NSAIDs are mediated through their inhibitory effects on cyclooxygenase (COX) activity and resulting decrease in prostaglandins (PGs). On the other hand, NSAID use is associated with gastrointestinal complications. Although PGs have a strong protective effect on gastrointestinal mucosa, the inhibition of COX by NSAIDs is not the sole explanation for the gastrointestinal side effects of NSAIDs. In this study, we examined the COX-independent mechanism involved in NSAID-induced gastric lesions. Using DNA microarray analysis, we found that CHOP, a transcription factor with apoptosis-inducing ability is induced by NSAIDs and treatment of cells with NSAIDs caused apoptosis in wild-type cells but not in CHOP-knock out cells. We also found that NSAIDs have membrane permeabilization activity. Furthermore, intracellular Ca2+ chelator, BAPTA-AM inhibited the NSAID-induced apoptosis and induction of CHOP. In vivo, we proposed that both COX inhibition at gastric mucosa and direct gastric mucosal cell damage (such as induction of apoptosis) by NSAIDs are required for the production of gastric lesions. Results showed that NSAID-induced apoptosis is mediated by permeabilization of cytoplasmic membranes, increase in the intracellular Ca2+ levels and induction of CHOP. Furthermore, results suggest that NSAIDs without membrane permeabilizing activity have reduced aastrointestinal side effects.

Cyclooxygenase-2 (COX-2) in Carcinogenesis and Selective COX-2 Inhibitors for Chemoprevention in Gastrointestinal Cancers

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have a property to inhibit tumor development in some cancers while it shows various side effects such as gastrointestinal bleeding and renal disorder. Selective cyclooxygenase (COX)-2 inhibitors (coxibs) were originally developed as one of anti-inflammatory drugs to avoid side effect of NSAIDs. Fortunately, the coxibs was also proved to have an inhibiting effect on tumorigenesis by many experimental studies using cell lines and animal models like NSAIDs. Since a randomized study for polyp chemoprevention by celecoxib in familial adenomatous polyposis (FAP) patients demonstrated a significant reduction in the number of colorectal polyps, the clinical use of celecoxib was approved for FAP patients. Three large trials using celecoxib (the Adenoma Prevention with Celebrex and the Prevention of Spontaneous Adenomatopus Polyps) or refecoxib (the Adenomatous Polyp Prevention on Vioxx) for the recurrence of colorectal polyps in patients with a history of colorectal adenoma polypectomized confirmed chemopreventive effects on colorectal adenoma but two of three trails alerted us a hazard of cardiovascular (CV) events. Thereafter, some coxibs were withdrawn from the market because they showed to increase risk of serious CV events including heart attacks and strokes. But recent reports concluded that a merit of the reduction in gastrointestinal events by coxibs exceeded a demerit of the increase in serious CV events. In this review, a role of COX-2 in carcinogenesis of gastrointestinal tract and a future of coxibs for chemoprevention are discussed.

Activity and potential role of licofelone in the management of osteoarthritis

Osteoarthritis is the most common form of arthritis. It is a progressive joint disease associated with aging. It may be found in the knees, hips, or other joints. It is estimated that costs associated with osteoarthritis exceed 2% of the gross national product in developed countries. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a mainstay in the treatment of inflammatory disease and are among the most widely used drugs worldwide. The main limitation in using NSAIDs consists in their side-effects, including gastrointestinal ulcerogenic activity and bronchospasm. The mechanism of action of these drugs is attributed to the inhibition of cyclooxygenase (COX), and, consequently, the conversion of arachidonic acid into prostaglandins. It is hypothesized that the undesirable side-effects of NSAIDs are due to the inhibition of COX-1 (constitutive isoform), whereas the beneficial effects are related to the inhibition of COX-2 (inducible isoform). Arachidonic acid can also be converted to leukotrienes (LTs) by the action of 5-lipoxygenase (5-LOX). Licofelone, a LOX/COX competitive inhibitor, decreases the production ofproinflammatory leukotrienes and prostaglandins (which are involved in the pathophysiology of osteoarthritis and in gastrointestinal (GI) damage induced by NSAIDs) and has the potential to combine good analgesic and anti-inflammatory effects with excellent GI tolerability. Preliminary data with this drug seem promising, but further well-designed clinical trials of this agent in the elderly will be necessary before a final evaluation is possible.

Chemoprevention of colorectal cancer – a new target needed?

Novel treatments for colorectal cancer (CRC) include chemoprevention. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the first to be studied and an inverse association was proven between their use and the development of invasive CRC. The numerous side effects of NSAIDs led, however, to the search for safer drugs. These have included Coxibs (selective COX-2 inhibitors). In this study, the role of coxibs in the chemoprevention of CRC is reviewed. Numerous in-vitro and in-vivo experiments have shown the effectiveness of coxibs in the chemoprevention of CRC. These have led to the registration of celecoxib by the USA Food and Drug Administration for the treatment of familial adenomatous polyposis. Further studies of coxibs have revealed an increased risk of serious cardiovascular events when compared with placebo. This finding has considerably decreased the opportunities for chemoprevention of CRC. The multi-directional activity of coxibs, which was the reason for their effectiveness against CRC development may be the key to proposing a new target area for chemoprevention. It has been shown that celecoxib partly inhibits the activity of NF-kappaB, transcription factor involved in inflammation and carcinogenesis pathways. Modulation of its activation may be the future of effective CRC chemoprevention.

Minimizing risks of NSAIDs: cardiovascular, gastrointestinal and renal

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating inflammation, pain and fever, but their cardiovascular, renal and gastrointestinal toxicity can result in significant morbidity and mortality to patients. Techniques for minimizing the adverse risks of NSAIDs include avoiding use of NSAIDs where possible, particularly in high-risk patients; keeping NSAID dosages low; prescribing modified-release and enteric-coated NSAIDs; prescribing cyclooxygenase-2-selective inhibitors where appropriate; monitoring for early signs of side effects; prescribing treatments designed to minimize NSAID side effects; and developing new therapeutic strategies beyond the inhibition of cyclooxygenase. All of the above strategies can be useful in reducing the risk of NSAID complications. The optimal use and management of NSAIDs involves an individualized paradigm approach to establish efficacy with optimal tolerability given the patient risk factors for adverse events.