Sunday, November 2, 2014

curcumin may hold promise for its anti-inflammatory impact on Alzheimer's



Sadly in September 2014, I lost my dad to Alzheimer Disease (AD), a sneaky and devastating disease.  My father was a rocket scientist with Grumman, managing the lunar module team that got the astronauts back to earth on Apollo 13.  So watching this brilliant man slowly slip away was very, very painful experience that endured for over an 8-10 year period.  That said, it gave me 8 years to prepare for his passing.
     Growing up, I saw my dad do everything that was possible to avoid getting dementia, having a very rich holistic and active lifestyle, doing chelation therapy 20 years ago, reading lots, using herbs and always seeking new challenges.  But once he got atrial fibrillation and was placed on coumadin (warfarin) and amiodarone to minimize the occurrence of stroke, I think his fate was set.  According to Ciccone (2013), amiodarone is a class III antiarrhythmic with many side effects that are known to significantly impact the thyroid, neuropathy, confusion, disorientation with the more severe adverse reactions being pulmonary fibrosis, abnormal liver functions and pulmonary toxicity.   And according to a study by the Intermountain Medical Center (2014), the difficulty in managing blood levels of warfarin doses can lead to a higher incidence of dementia. That said, my dad was always diligent with utilizing a warfarin clinic, so I can only imagine what is happening out there with the rest of the population that is not so attentive.
     I have personally found that this disease is not only dreaded by the patient, but also by the family.  It was very, very painful admitting my dad to the Veterans home when his “sun downing” made him a bit difficult to handle during night time attempts at assisting him or changing the bedding.  Amazingly, all through his decline, he remained mild, polite and kind throughout the daytime, except during those moments with night time “sun downing”, so with consideration for their long term care insurance, the choice for  the Veterans home was the best, safest choice although emotionally traumatic for all of us.  I think we all had more difficulty with his nursing home admission than with his death, although both felt pretty bad.
     My wisdom for the treatment of Alzheimer's disease is to include family or friends in the rehabilitation process, my dad always did better in my presence, both as a PT and daughter, as I stimulated him and worked with whatever I could.  I worked to en-train my dad's nervous system as he was still somewhere in there.  Both my family and his aide learned about exercise and respiratory techniques, and they read up on activities and music commonly used with dementia patients.  Up until his death, I was able to get him to smile, respond and even chatter.  But as typically stated in the literature, infection is one of the leading causes of death in Alzheimer’s, and in my dad’s case, a few frequent bouts of aspiration pneumonia finally took its toll in spite of the special soft diets, tooth care, suctioning, respiratory therapy and IV antibiotics. 
     In retrospect, and as a result of my research papers required for graduate school, I feel my dad had foci of infections that did not respond to the chosen antibiotics, as his typical pattern would be to do well for several weeks after its discontinuation and then just vomit for “no apparent reason”.  This last pneumonia event was 2 weeks after a previous bout, having had a good week and a nice lunch, he simply vomited after saying goodbye to my mom.  He was immediately suctioned and had respiratory therapy within 45 minutes, but the infection never seemed to respond, and he passed away several days later on his 82nd birthday and 60th anniversary, having had all of us around him. 
     As a holistic therapist, I did use some turmeric (curcumin) with my dad, but his swallowing difficulty (mild dysphagia) made that an arduous endeavor unless mixed into his food, but that probably limited its bioavailability.  According to Morales, Guzman-Martinez, Cerda-Troncoso, Farias and Maccioni (2014), they found that curcumin may hold promise for its anti-inflammatory impact on AD by disrupting the inflammatory response and self-aggregation of the τ protein.  
     What is the answer, do more aggressive antibiotics for repeated bouts of resistant pneumonia that can ravage a person's health or simply let this horrible mind sucking disease take them?
References
Ciccone, C. D. (2013). Drug guide for rehabilitation professionals. Philadelphia, PA: F.A.  Davis Company.
Intermountain medical center (2014). Patients with atrial fibrillation at higher risk of developing dementia when meds are out of range.  Retrieved from http://www.sciencedaily.com/releases/2014/05/140509203841.htm
Morales, I., Guzman-Martinez, L., Cerda-Troncoso, C., Farias, G. A. & Maccioni, R. B. (2014). Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches.  Front. Cell. Neurosci.   doi: 10.3389/fncel.2014.00112

Opiates in a nasal spray?



     Has anyone heard of nasal sprays for opiates?  Maciejeweski (2012) found there were off-label uses of agonistic opioids that included intra-articular and intranasal routes of administration as well as peripheral nerve blocks.   According to Steenblik et al. (2012), intranasal (IN) applications of an opioid called sufentanil has been effectively utilized in clinics at winter resorts, urgent care facilities and emergency rooms for its rapid analgesic impact on acute injuries.  They found that although most IN research was performed in the pediatric population, IN was actively being utilized in adult populations in spite of the higher volume of medication required to produce an effective analgesia.  Kendall, Maconochie, Wong & Howard (2014) also found an atomized opioid called diamorphine that was quite effective in the rapid relief of moderate to severe pain as in case of fracture and burns. 
     Sufentanil (Sufenta) is a synthetic opioid that is similar in action to fentanyl, but is better suited for IN administration due to its higher potency, lower cost and tendency to cause less adverse effects within a wide dose range (Steenblik et al., 2012).  Diamorphine is made from a semisynthetic derivative of morphine, is highly lipid soluble and crosses the blood brain barrier better than morphine, therefore producing a more rapid and intense central nervous system (CNS) response that is desired for analgesia in acute injuries ( Kendall, Maconochie, Wong & Howard, 2014). These authors also reported this medication has the sedation and gastrointestinal issues of nausea or vomiting oftentimes seen with other opioids, as well as a mild nasal irritation or burning sensation correlating with the volume of spray.
     Sufentanil’s action occurs as it binds to opioid receptors of the CNS, thus diminishing the response to pain and depressing the CNS (Ciccone, 2013).  He went on further to state that sufentanil is mostly metabolized in the liver, although some metabolism occurs in the small intestine and it has an intravenous bioavailability of 100%.  He also noted that the most dangerous side effects were apnea and thoracic rigidity, cardiac arrest, laryngospasm and anaphylaxis (p. 1022).  The most fatal drug to drug interaction is the combination with MAO inhibitors within a 2 week time frame, and less severe reactions may occur in the presence of other CNS depressants like alcohol, sedatives, antidepressants or other opioids.
     According to Kendall, Maconochie, Wong & Howard (2014), there are benefits to opiate nasal spray with its fast action compared to oral medications, plus it is as effective as an intravenous administration, but with quicker implementation in fast paced situations.  These authors felt this nasal spray demonstrated a good safety profile, but with that said, their study was limited to the pediatric population, an unfortunate limitation in this study. 
    
References
Ciccone, C. D. (2013). Drug guide for rehabilitation professionals. Philadelphia, PA: F. A.  Davis Company.
Kendall J., Maconochie, I., Wong, I. C. K. & Howard, R. (2014).  A novel multipatient intranasal diamorphine spray for use in acute pain in children: pharmacovigilance data from an observational study. Emerg Med J, 0,1-5.  doi:10.1136/emermed-2013-203226
Maciejewski, D. (2012). Sufentanil in anaesthersiology and intensive therapy.  Anaesthesiology Intensive Therapy, 44, 35-41.
Steenblik, J., Goodman, M., Davis, V., Gee, C., Hopkins, C., Stephen, R., & Madsen, T. (2012). Intranasal sufentanil for the treatment of acute pain in a winter resort clinic. American Journal Of Emergency Medicine, 30(9), 1817-1821. doi:10.1016/j.ajem.2012.02.019

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