NSAIDs: Balancing the Risks and Benefits - Essay Example

Introduction: Non-steroidal anti-inflammatory drugs, frequently truncated to NSAIDs are also referred to as non-steroidal anti-inflammatory agents/analgesics (NSAIAs) or non-steroidal anti-inflammatory medicines (NSAIMs). The term non-steroidal distinguishes these drugs from steroids, which among a wide range of other effects, have a similar eicosanoid-depressing, anti-inflammatory action. They are a class of drugs that provides anesthetic (painkilling) and antipyretic (fever-reducing) paraphernalia and when administered in higher doses, they cause anti-inflammatory effects. As analgesics, NSAIDs are strange in that they are non-narcotic and thus are used as a non-addictive alternative to narcotics (Sundaram, 2014) The most common members of this group of drugs such as aspirin, ibuprofen and naproxen are all available over the counter in most countries. Acetaminophen (parecetamol) is not considered an NSAID because it has only little anti-inflammatory activity. It treats pain mainly by blocking COX-2 mostly in the central nervous system, but not much in the rest of the body.NSAIDs work by inhibiting the activities of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). They achieve their function by synthesizing prostaglandins and thromboxanes (Hughes, 2008 p. 100). It is believed that inhibiting COX-2 leads to the anti-inflammatory, analgesic and antipyretic effects. It has been discovered that, those NSAIDs that inhibit COX-1, particularly aspirin, may cause gastrointestinal bleeding and ulcers. For this reason, the use COX-2 selective inhibitors may be preferred to COX-1 inhibiting NSAIDs. This paper will, therefore, primarily focus on the cardiovascular safety or effect of such NSAIDs. The Mechanism of action of NSAIDs According to John Vane (1927-2004), in his Nobel-winning works “the Mechanism of action of aspirin” he elevated that, most NSAIDs act as nonselective inhibitors by targeting enzyme cyclooxygenase (COX) (Bruera & Portenoy, 2009 p. 271). They achieve their goal by inhibiting both the isoenzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Most of this inhibition caused by NSAIDs is competitively reversible (although at fluctuating degrees of reversibility), except the mechanisms of aspirin, which is irreversible inhibition. COX more specifically works as it catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (a compound that is derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act among other things as messenger molecules in the process of inflammation. Cyclooxygenase-1 (COX-1) is a constitutively articulated enzyme with a "house-keeping" role in regulating many normal physiological processes. One of these physiological processes that it has been charged with the role of regulating is the protection of stomach lining. It does so by using prostaglandins, which serve a protective role by preventing the stomach mucosa from being eroded by its own acid. On the other hand, cyclooxygenase (COX-2) is an enzyme, which is predominantly expressed in the inflammation process; therefore, its inhibition produces the desirable and required effects of NSAIDs. When nonselective COX-1 or COX-2 inhibitors (such as aspirin, ibuprofen, and naproxen) lower stomach prostaglandin levels, ulcers of the stomach or duodenum internal bleeding can result. A lot of research has been put into fully understanding how these NSAIDs really work. NSAIDs have been studied in various tests to understand how they affect and manipulate each of these enzymes. It is evident that no single study has been found to have similar findings. While the assays reveal differences, unfortunately, different assays provide differing ratios. All these studies find their roots in the discovery of COX-2, which consequently led to research to development of selective COX-2 inhibiting drugs that do not cause gastric problems typical of previous NSAIDs. Other drugs such as Paracetamol have been found to carry some inflammatory effects associated with NSAIDs. However, Paracetamol (acetaminophen) is not entirely considered as an NSAID due to its little anti-inflammatory activity. It has been found to treats pain mainly by blocking (cyclooxygenase-2) COX-2 mostly in the central nervous system, but not much in the rest of the body. It is due to this reason that it has failed to fall into the category of NSAIDs. Conversely, many aspects of the mechanism of action of NSAIDs remain mysterious, and for this reason further cyclooxygenase (COX) trails are assumed. The study of the (cyclooxygenase-3) COX-3 pathway was thought to help fill some of this gaps that COX-1 and COX-2 leave vacant, but recent findings make it appear questionable that it plays any substantial role in humans and alternative explanation models are projected. Medical Uses of NSAIDs NSAIDs are commonly used for the management of either acute or chronic conditions where pain and inflammation are existent. There are ongoing studies that are trying to dig into the possibility and potential of NSAIDs usage in the prevention of colorectal cancer (Bruera & Portenoy, 2009 p. 266). However, it is a well-established fact that NSAIDs are generally used for the symptomatic relief of the following conditions; Osteoarthritis, Rheumatoid arthritis, Low back pain, Mild-to-moderate pain due to inflammation and tissue injury and Inflammatory arthropathies such as ankylosing spondylitis, psoriatic arthritis and Reiter's syndrome It is further evident that NSAIDs are used in the treatment of Tennis elbow, Headache, Migraine, Acute gout, Dysmenorrhoea (menstrual pain), Metastatic bone pain, Postoperative pain, Muscle stiffness and pain due to Parkinson's disease, Pyrexia (fever) and Ileus Renal colic (Mukherjee, 2001, p. 951). In some cases, NSAIDs are also given to neonate newborns whose ductus arteriosus are not closed within 24 hours of birth. NSAIDs are also used in the acute pain caused by gout. This is because they inhibit urate crystal phagocytosis as well as inhibition of prostaglandin synthase. (Dickman, 2010, p. 31). Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for the inhibition of platelet aggregation, this goes a great was in ensuring that gastrointestinal bleeding and ulcers are prevented. This is useful in the management of arterial thrombosis and prevention of adverse cardiovascular events. Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane A2 (Supuran & Winum, 2009). It is apparent that NSAIDs have a wide range of uses and therefore play a very significant role in the treatment and care of most painful inflammations. Cardiovascular safety of NSAIDs Most NSAIDs apart from aspirin, both newer selective COX-2 inhibitors, and traditional anti-inflammatory, have been found to increase the risk of myocardial infarction and subsequently strokes. They are not recommended for patients who have had a preceding heart attack as they increase the risk of death and or recurring. Naproxen has been seen to seem the least harmful of the non-steroidal anti-inflammatory drugs. Studies have indicated that the uses of NSAIDs aside from low aspirin doses are associated with a doubled risk of heart failure in people without a history of cardiac disease. In people with such a history, use of NSAIDs was associated with a more than 10-fold increase in heart failure. This is definitely the reason for alarm. If this link is proven, researchers assessments indicate that NSAIDs would be liable for up to 20 percent of hospital admissions for congestive heart failure. In people with heart failure, NSAIDs increase mortality risk with the hazard ratio approximated to be 1.2-1.3 for naproxen and ibuprofen. This ratio fluctuates for different NSAIDs as elaborated in researches. 1.7 For rofecoxib and celecoxib and 2.1 for diclofenac. The evidence indicates that the effect of these NSAIDs cannot be overlooked; the exhibited cardiovascular risks should prompt evaluation of a broader range of alternatives. According to The BMJ is one of the most influential general medicine journals in the world, in a study to find out which NSAID can be deemed safest for patients with high cardiovascular risk, it found out that millions of patients with chronic musculoskeletal symptoms are long term users of non-steroidal anti-inflammatory drugs (NSAIDs). Regrettably, these drugs have common and potentially severe adverse effects, including renal impairment, gastrointestinal complications, and as has been shown for selective cyclo-oxygenase-2 inhibitors, cardiotoxicity. The journal further retaliates that the last effect is particularly worrying because many patients have both cardiovascular disease and musculoskeletal disease. Given that both mechanistic and clinical data suggest that the individual, NSAIDS may have different cardiovascular risk profiles (Ray, 2011, p. 78). The journal used network meta-analysis to assess the cardiovascular safety of individual. It discovered that all cyclo-oxygenase-2 inhibitors studied in large sample controlled trials have been found to confer an increased risk of serious cardiovascular disease. Furthermore, rofecoxib increases risk more than naproxen. This suggests that patients with a high risk of cardiovascular disease should avoid cyclo-oxygenase-2 inhibitors. The research concluded that most NSAIDs increase the risk of cardiovascular disease but in different ratios (Ray, 2011, p. 56). According to the cardiovascular journal of Africa, there is no doubt that NSAIDs and COXIBs form the backbone for managing pain and inflammation in arthritis. Overall, at therapeutically equivalent doses, both NSAIDs and COXIBs provide equivalent analgesic and anti-inflammatory effectiveness (McGettigan & David, 2006, p. 1634). However, the gastrointestinal risk associated with NSAIDs is considerable. The journal further states that, more recently, the cardiovascular risk associated with NSAIDs and COXIBs has become a huge concern for all the stakeholders involved (Moodley, 2008, p. 102). NSAIDs have been proven to benefit the young without major risks of adverse gastrointestinal or cardiovascular events as opposed to patients with a previous history of serious gastrointestinal complications and the elderly, who could be at risk, do require alternatives. COX-2 selective inhibitors (COXIBs) have significant benefits over NSAIDs in reducing the incidence of serious gastrointestinal complications such as perforations, ulcers, and gastric bleeding. Currently, two oral COXIBs are available, celecoxib and lumiracoxib, and one parenteral COXIB, parecoxib. Celecoxib has been on the market for longer and had the largest body of evidence that indicates that they are fairly safer as compared to NSAIDs (Moodley, 2008 p. 104). The cardiovascular journal of Africa supplementary states that the older NSAIDs, such as meloxicam, with preferential COX-2 inhibition, do not provide good evidence that indicates their good long-term evidence of reducing the incidence of serious gastrointestinal complications. However, these agents do have evidence of tolerability, for example, reducing the less-serious gastrointestinal effects, mainly dyspepsia. The South African Rheumatoid Arthritis Association's guidelines, amended in November 2005 recommend COXIBs for elderly patients of above 60 years with previous gastropathy and those on warfarin and or corticosteroids, providing they do not have contra-indications (Moodley, 2008, p. 106). The National institute for Clinical Excellence (NICE), cautions when prescribing COXIBs for patients with risk factors for heart disease. The institute additionally advises that, it should be noted that for those patients without any cardiovascular complications but with gastrointestinal risk factors or on aspirin, it may be necessary to add a proton pump inhibitor (PPI) (Harbin et al., 2014, p. 67). PPIs, however, provide little benefit for bleeding and ulceration of the lower intestine. One concern of this low-grade bleeding is anemia and a general feeling of malaise in patients with rheumatic disease. Current evidence suggests that COXIBs such as rofecoxib and celecoxib do not increase small intestinal permeability and that celecoxib does not cause lower intestinal bleeding and may be of benefit to those patients with lower gastrointestinal complications. All this are generally attempts aimed at finding an alternative to the unsafe NSAIDs, researches indicate light at the end of the tunnel but there is a long way to go in stabilizing these NSAIDs. The cardiovascular journal concludes by asserting that, in patients at risk for cardiovascular complications, both NSAIDs and COXIBs have been shown to increase the risk of myocardial infarctions (MI), hypertension and heart failure. Studies comparing COXIBs and non-specific NSAIDs should be approached interpreted with caution. A lot of factors have to be involved in the comparison for instance; one needs to take into account the underlying baseline cardiovascular risk of the populations being compared. COXIBs appear to be prescribed preferentially to patients who were at an increased risk of cardiovascular events compared with patients prescribed non-specific NSAIDs (Moodley, 2008, p. 107). Conclusion From the elaborate facts stated in this assessment, it is undoubtedly obvious that the Non-steroidal anti-inflammatory drugs increase the risk of cardiovascular effects by a great deal. Resources must be put into the finding of safer and tolerable alternatives. Although they have a wide range of medical uses, NSAIDs are an epitome of pure medical gambling. The effects they carry cannot be overlooked. COX-2 selective inhibitors (COXIBs) have risen as an alternative to NSAIDs and offer the elderly less risk of recurring heart attacks. The bottom line is that new, advanced and safer alternatives have to be made available. . Bibliography Bruera, E. D., & Portenoy, R. K., 2009, Cancer Pain Assessment and Management. Cambridge, Cambridge University Press. http://dx.doi.org/10.1017/CBO9780511642357. Dickman, A., 2010, Drugs in palliative care. Oxford, Oxford University Press. Harbin, Megan, Ricky D. Turgeon, and Michael R. Kolber."Cardiovascular safety of NSAIDs." 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