Free Shipping on orders over $99

Non-Steroidal Inflammatory Drugs: NSAIDs Safety and Issues

Pain | November 14, 2014 | Author: The Super Pharmacist

Pain

Non-Steroidal Inflammatory Drugs: NSAIDs Safety and Issues

Non-steroidal anti-inflammatory drugs (NSAIDs) are chemicals that act as inhibitors of inflammation in the body. Inflammation is associated with a wide range of adverse effects and disorders, including pain, tissue damage, joint deterioration and cancer. Drugs that can prevent the expression of molecules that cause or promote inflammation, essentially a system chemical reaction resulting in the increase of heat or irritation in the affected cells, are beneficial in a number of conditions and illnesses. The most prominent of these are steroids.

Steroids are molecules similar in structure to many hormones and other physiologically active compounds. Therefore, they may have extensive and profound side-effects due to their ability to partially mimic and eventually disrupt the biological effects of hormones. Steroids may cause adverse reactions such as reduced bodyweight control, abnormal emotional or behavioural responses, hypertension and hypogonadism. These drugs may be beneficial in many cases, but are often reserved for advanced or severe illness due to this side-effect profile.

Other drugs with similar properties are available as a more front-line (or over-the-counter) treatment for conditions in which inflammation may be a factor. These mostly fall into the category of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit enzymes called cyclo-oxygenases. Since these enzymes play an important role of 'pro-inflammatory' biological molecules such as prostaglandins, inhibiting them may significantly reduce inflammation.

Some NSAIDs are among the most popular and established painkillers, and are in very widespread use. An example of this is aspirin, one of the most common drugs taken worldwide. Estimates suggest that approximately 120 billion tablets (at an average of 300mg each) are consumed each year. Other common drugs classed as NSAIDs include:

  • Naproxen
  • Ibuprofen
  • Indomethacin
  • Diclofenac
  • Celecoxib: This is one of a newer subclass of NSAIDS designed to inhibit just one subtype of cyclo-oxygenase, COX-2. The rationale behind their development was to improve NSAIDs safety profile associated with traditional non-selective cyclo-oxygenase inhibition, but there is considerable ambiguity as to whether this was achieved in reality. Many 'coxibs' are currently restricted from some markets and sold with increased caution in others.

These NSAIDs are associated with effective treatment of conditions in which pain and/or inflammation are major symptoms. These include:

  • Many forms of arthritis (joint degeneration), including rheumatoid, juvenile, psoriatic, and osteodegenerative arthritis
  • Headaches
  • Migraine (in conjunction with other migraine drugs)
  • Menstrual cramps
  • Systematic lupus erythromatosus
  • Bone disorders such as ankylosing spondylosis

NSAID use is also associated with a range of side-effects and adverse reactions, some of which overlap with those of steroids (i.e. due to long-term repression of pro-inflammatory molecules). They have been linked to the risk of other adverse effects, which may extend to that of cancer. Recently, NSAIDs were thought to influence the risk of non-Hodgkin's lymphoma. However, studies investigating this link often find no such association.

A systematic review of 17 studies concluded that there was no association between all NSAID types and all subtypes of non-Hodgkin's, and that aspirin use was associated with a reduced risk of one subtype of the condition, chronic lymphocytic leukemia. On the other hand, some of these studies found NSAIDs with the exception of aspirin were associated with the increased risk in women. However, this association may not necessarily be causative; it is likely that these patients were simply taking NSAIDs to alleviate the symptoms of non-Hodgkin's before being diagnosed.

Many studies into this link do not take this into account. Another study including nearly 150,000 participants found an association between NSAIDs and the incidence of non-Hodgkin's lymphoma, but none for most subtypes of the condition - except follicular lymphoma - when this factor was corrected for. In addition, studies on the influence of NSAIDs on the risks of cancer are often not consistent in the patient or demographic groups (for example, patients with rheumatoid arthritis may have an increased risk of cancer that is associated with excess inflammation rather than NSAID use), doses, and duration of drug intake incorporated, making analysis of this association more difficult. In addition, there is evidence that NSAIDs may actually reduce the risks of certain types of cancer, due to their inhibition of prostaglandin synthesis in the body. The risk of the more common side-effects is often influenced by their intake in high doses or over long periods of time.

Long-term Side Effects of NSAIDs

Liver damage

Liver enzyme elevation is a common adverse effect of many diseases and drugs. In the case of prolonged or high-dose NSAID use, it may indicate additional stress placed on the liver as it tries to maintain the production of the enzymes necessary to adequately metabolise the drugs. In severe cases, this may lead to extensive liver damage.

Gastrointestinal damage

NSAIDs are thought to affect the health and integrity of the digestive system in two main ways:

  • The increased secretion of gastric acid, and
  • A resultant erosion of inner layers of the tract, against which prostaglandins would normally protect.

Cyclo-oxygenases and prostaglandins play a much more beneficial role when in the gut lining. Chronic NSAID intake may result in many adverse gastrointestinal effects, including;

  • Vomiting
  • Nausea
  • Indigestion
  • Acid reflux
  • Diarrhoea
  • Ulcers (lesions in the gastric tract), which may lead to bleeding
  • Perforation, or the nearly complete 'wearing through' of the lining, also associated with bleeding

The risk of these side-effects may be increased by pre-existing conditions in which ulcers and/or bleeding are a component, such as inflammatory bowel disease. Up to 4% of people over 50 who take NSAIDs regularly may experience severe events such as perforation or bleeding. Gastrointestinal side-effects are also associated with the use of steroids.

Cardiovascular disorders

With the singular exception of low-dose aspirin, regular NSAID use may increase the risk of disorders such as myocardial infarction and stroke. This is influenced by a pre-existing risk for such conditions.

Rofecoxib, an NSAID similar to celecoxib, was found to be associated with a significantly higher rate of myocardial infarction (0.4%) in comparison with that of naproxen (0.1%) and was subsequently removed from the market in the United States. Another large-scale trial investigating the safety of rofecoxib found that it was associated with increased blood pressure in 8% of cardiovascular patients, compared to 1.3% in healthy controls.

Renal disease and failure

Prostaglandins also play a role in the regulation of kidney function, which means their inhibition may increase the risk of renal dysfunction. Some estimates suggest that up to 5% of those taking NSAIDs may develop these kidney problems. These range from fluid retention to sudden-onset kidney failure. The latter may be reversible, but leave the patient at a higher risk of chronic kidney deterioration.

Others

NSAIDs have a high probability of other mild adverse effects, including acute headache and dizziness.

www.superpharmacy.com.au  Australia’s best online discount chemist

References

Bello AE, Holt RJ. Cardiovascular Risk with Non-steroidal Anti-inflammatory Drugs: Clinical Implications. Drug safety : an international journal of medical toxicology and drug experience.2014;37(11):897-902.

Wajchenberg BL, Giannella-Neto D, da Silva ME, Santos RF. Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.2002;34(11-12):616-621.

Guignat L, Bertherat J. [Cushing syndrome: When to suspect and how to confirm?]. Presse medicale (Paris, France : 1983).2014;43(4 Pt 1):366-375.

Warner TD, Mitchell JA. Cyclooxygenase-3 (COX-3): filling in the gaps toward a COX continuum? Proceedings of the National Academy of Sciences of the United States of America.2002;99(21):13371-13373.

van Hoof JJ, Cents MH, Megens NM, van der Tang SJ. Druggists and pharmacists as gatekeepers: sales routines and compliance with sales protocols for over-the-counter naproxen 275 mg medicines in the Netherlands. Health policy (Amsterdam, Netherlands).2014;117(3):353-360.

Nalamachu S, Wortmann R. Role of indomethacin in acute pain and inflammation management: a review of the literature. Postgraduate medicine.2014;126(4):92-97.

Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.2013;16(5):821-847.

Pascucci R. Use of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 (COX-2) inhibitors: indications and complications. JAOA: Journal of the American Osteopathic Association.2002;102(9):487-489.

Ye X, Casaclang N, Mahmud SM. Use of non-steroidal anti-inflammatory drugs and risk of non-Hodgkin lymphoma: a systematic review and meta-analysis. Hematological oncology.2014.

Teras LR, Gapstur SM, Patel AV, et al. Aspirin and other nonsteroidal anti-inflammatory drugs and risk of non-hodgkin lymphoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.2013;22(3):422-428.

Baecklund E, Iliadou A, Askling J, et al. Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis & Rheumatism.2006;54(3):692-701.

Gierach GL, Lacey JV, Jr., Schatzkin A, et al. Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health-AARP Diet and Health Study. Breast cancer research : BCR.2008;10(2):R38.

Daugherty SE, Pfeiffer RM, Sigurdson AJ, et al. Nonsteroidal antiinflammatory drugs and bladder cancer: a pooled analysis. American journal of epidemiology.2011;173(7):721-730.

Gargallo CJ, Sostres C, Lanas A. Prevention and Treatment of NSAID Gastropathy. Current treatment options in gastroenterology.2014;12(4):398-413.

Pan Y, Zhang L, Wang F, Li X, Wang H. Status of non-steroidal anti-inflammatory drugs use and its association with chronic kidney disease: A cross-sectional survey in China. Nephrology (Carlton, Vic.).2014;19(10):655-660.

Stitham J, Vanichakarn P, Ying L, Hwa J. Cardiovascular pharmacogenetics of anti-thrombotic agents and non-steroidal anti-inflammatory drugs. Current molecular medicine.2014;14(7):909-931.

backBack to Blog Home