Sunday, November 2, 2014

NSAIDs--the good, bad and ulgy side of these medications



     Aspirin (acetylsalicylic acid) and ibuprofen are the more popular over-the-counter (OTC) non-steroidal anti-inflammatory drugs (NSAIDs) seen in many outpatientclinics.  Hauser (2010) reported that globally, especially in the more developed countries, over 25% of geriatric patients suffering from osteoarthritis (OA) will take NSAIDs to address pain (p. 305).  According to Ciccone (2007, p. 199), aspirin is classified as a salicylate, but is the most representative example of NSAIDs due to its anti-inflammatory, moderate analgesic, antipyretic and anticoagulation properties.   He reports the anti-inflammatory property of acetylsalicyclic acid results from the inhibited synthesis of prostaglandins, an endogenous lipid-like substance that regulates cellular function (p. 200).  Hauser (2010) agrees the mechanism of NSAIDs is caused by the inhibition of both cyclooxygenase-1 (COX 1) and cyclooxygenase-2 (COX 2) enzymes, with COX 2 being the newer and kinder on the gastrointestinal tract, but both limiting the prostaglandin messenger necessary for inflammation . He expressed strong concerns over the treatment of osteoarthritis (OA) with NSAIDs and suggested focusing the medical intervention on the articular cartilage breakdown or pain of OA versus swelling, favoring a more conservative approach to NSAIDs with lower dosages and shorter durations (p. 311).
     There are other pro-inflammatory lipid-like substances that are similar to prostaglandins called leukotrienes and thromboxanes, with all three being collectively known as eicosanoids (Ciccone, 2007, pp. 200-201).  Eicosanoids are powerful at regulating issues like inflammation, but their exact action on the immune system is still not totally understood (Pratt & Brown, 2014, p. 3).  However, it is known that in the presence of dysfunctional regulation of inflammatory and anti-inflammatory mediators or eicosanoids, this mechanism has a direct impact on the course of a disease (Pratt & Brown, 2014, p. 5).  Hauser (2010) found that prostaglandins stimulate the proliferation of chondrocytes, a very beneficial aspect of cartilage healing, but also a mechanism that gets blocked by NSAIDs.  According to Nasjletti (1998), the same is true for blood pressure regulation, where eicosanoids mediate angiotensin-dependent hypertension through the balancing of prohypertensive and antihypertensive functions that may be hindered by NSAIDs (p.194).
          Hauser (2010) feels strongly that the adverse long term side effect of aspirin is the degradation of articular cartilage caused by the degenerative impact on the cartilage matrix and possibly the reduced compensatory/protective joint strategies caused by local analgesia (p. 316).  He believes in situations of osteoarthritis, oftentimes characterized as a condition of joint degeneration that is usually without swelling or heat, the use of anti-inflammatory drugs like NSAIDs for a non-inflammatory condition can be very problematic to the individual’s cellular healing (p. 311).  He found in some cases where matrix alterations or internal changes to mechanical properties of the cartilage had occurred, the result was consistent with an increased incidence of bone cysts, nodules or spurs (p. 308).  However, on a more positive note, Wang et al. (2003) had an in vitro study showing aspirin’s promise of inhibiting growth of H pylori, as well as value in increasing the organism’s susceptibility to antimicrobials, however suggesting further in vivo research aimed at drug resistance and virulence was needed (p. 494).
     Adverse drug reactions (ADR) or side effects of acetylsalicylic acid commonly seen in my clinic are tinnitus, gastric distress and easy bruising.  Ciccone (2013) finds the most severe reactions are gastric bleeding, anaphylaxis and laryngeal swelling, but to a lesser degree a skin rash, anemia and abdominal pain (p. 80).  Caution must be taken during physical therapy to minimize bruising during manual therapy and therapeutic exercises, carefully monitoring for rashes, blood pressure, shortness of breath, nausea or abdominal pain as it may be related to an allergic reaction or bleeding associated with acetylsalicylic acid (p.80). 
     The ugly side of drug to drug interactions must now be written on the front of prescription labels, mandated by the FDA, stating that any prescription and OTC drug containing NSAIDs, blood thinners or steroids may cause bleeding or stomach ulcers with this product (Hauser, 2010, p. 318).  Ciccone (2013) further highlighted that ibuprofen may decrease the antiplatelet effect, pencillins and oral hypoglycemics may be potentiated, sulfonamides and methotrexate may be potentiated, ACE inhibitors may be limited and antacids may limit the salicylate effect.   This drug is well absorbed in the small intestine and rapidly distributed throughout, crossing the placenta and entering breast milk, so it should not be used in children, new mothers or in pregnancy (p. 81).
     The main food to drug interaction occurs during the over-consumption of foods that increase the acidity of urine as this may increase serum salicylate levels (Ciccone, 2013, p. 81).  Herbals that increase the risk of bleeding are arnica, chamomile, clove, garlic, gingko, ginseng and ginger (p. 81).  Hauser (2010) also believes limiting alcohol consumption is necessary to minimize the risk of bleeding and ulcers (p.318).
     Finally, according to Scott, Khan, Roberts, Cook and Duronio (2004), inflammation is a complex, integrated cellular phenomenon that encompasses many mechanisms from cell death and cellular debridement to tissue proliferation and cellular regeneration, so having assumptions that pain directly correlates with inflammation is misguided and may even be harmful to the healing process (p. 372-375).  The use of NSAIDs must be prescribed or taken with great caution and accuracy, utilizing physical therapy modalities, complementary and alternative medicine, exercise, proper body and joint mechanics, as well as good nutrition and hydration to achieve the goal of pain relief and improved function.
References
Ciccone, C. D. (2007). Pharmacology in rehabilitation (4th ed). Philadelphia, PA: F. A. Davis
        Company.
Ciccone, C. D. (2013). Drug guide for rehabilitation professionals. Philadelphia, PA: F. A.
       Davis Company.
Hauser, R. A. (2010). The acceleration of articular cartilage degeneration in osteoarthritis by
        nonsteroidal anti-inflammatory drugs.  Journal of Prolotherapy, 2(1), 305-322.  Retrieved from
Nasjletti, A. (1998). Hypertension, 31, 194-200.  doi: 10.1161/01.HYP.31.1.194
Pratt, C. & Brown, C. (2014). The role of eicosanoids in experimental Lyme arthritis. Frontiers in cellular
        and infection microbiology, 469. doi:10.3389/fcimb.2014.00069
Scott, A., Khan, K. M., Roberts, C. R., Cook, J. L. & Duronio, V. (2004). What do we mean by the term
        ‘‘inflammation’’? A contemporary basic science update for sports medicine.  Br J Sports Med, 38,
        372–380. doi: 10.1136/bjsm.2004.011312
Wang, W. H., Wong, W. M., Dailidiene, D., Berg, D. E., Gu, Q., Lai, K. C.,…Wong, B. C. Y. (2003).  Aspirin
        inhibits the growth of Helicobacter pylori and enhances its susceptibility to antimicrobial agents. 
        Gut, 52, 490-495. doi:10.1136/gut.52.4.490

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