Everyday Medications that Increase the Risk of Heart Attack

Data out of Stanford University suggest that Proton Pump Inhibitors (PPI’s) such as Prilosec, Prevacid, and Nexium are associated with a higher risk of heart attack.  Published in the journal PLOS One online, researchers looked over 2.9 million patients over a several year period to determine if patients who took PPI’s for gastro esophageal reflux had an increased risk for myocardial infarction than patients who did not.  Concern was raised when scientists discovered that PPI’s potentially reduced the antiplatelet effect of clopidogrel, a drug use to prevent clotting after a heart attack or stroke.  The clopidogrel is used after heart attack to prevent clotting which could lead another heart attack.  They were concerned that if heart attack was raised in this population, it could extend to lower risk patients.

The study showed that patients taking PPI’s had a 16% increased risk of heart attack.  H2 Blockers, such as Zantac and Pepcid were not associated with an increase risk.  Perhaps more importantly, the risk was not just associated with high risk categories such as having had a previous heart attack, the elderly or taking clopidogrel.  It was applicable to all ages and risk groups.

The study has several limitations including the attempt to look back at charts and determine what medications are being taken.  Often patients will take over the counter PPI’s and may not be accurately reporting it to their physician.  Also, retrospective analyses like this are subject to certain biases and are not as valuable as preplanned double-blind clinical trials.  However, the large number of patients reviewed does give the study significant credence.

PPI’s are one the most commonly used medications in the United States and around the world, with over 113 million prescriptions filled globally each year.  PPI’s are used to treat stomach and intestinal ulcers and heartburn, as well as to prevent gastrointestinal bleeding from NSAID’s in higher risk populations.  NSAID’s have been associated with a number of serious complications in addition to bleeding ulcers including kidney and liver issues, fluid retention with swelling in the legs, elevated blood pressure and possibly increasing the risk of heart attack.

Medications that are often used to treat or prevent the side effects of another medication create a potentially vicious cycle for patients who will ultimately end up taking more and more medications to manage an illness. The risk of adverse events increases with the number of medications prescribed, and the number of medications prescribed increases with age.

The avoidance of polypharmacy and therefore reducing the risk of dangerous medication side effects is crucial for patients and providers.  Alternative therapies, such as FDA regulated medical foods, which by definition must be on the FDA GRAS list (generally recognized as safe), may have similar efficacy to standard pharmaceuticals but without the side effects. Understanding the risks and benefits of medications is an important part of being a patient and a healthcare provider. Exploring the medication options that may be better tolerated is something every patient and physician should do.

 

Safer Options for Pain Management

Pain is complex and there are several treatment options to choose from depending on the type of pain you are experiencing including medications, therapies and mind-body techniques.  The most common treatment consists of analgesics:  narcotic (opioid) and non-narcotic (non-opioid) analgesics.

Narcotics vs NSAIDS
Primary Differences Between Narcotics and NSAIDs

Narcotic analgesics are derived from or related to opium.  Opioids bind to opioid receptors which are present in many regions of the nervous system and are involved in pain signaling and control.  Opioid analgesics relieve pain by acting directly on the central nervous system.  They block incoming pain signals but also work in other parts of the brain, modulating pain receptors in the nervous system, primarily located in the brain and the spinal cord.

Non-opioid analgesics or NSAIDs work by blocking the production of prostaglandins by inhibiting the cyclooxygenase enzyme and therefore decreasing the formation of pain mediators in the peripheral nervous system.   Non-opioids work more directly on injured or inflamed body tissue. In a basic sense, opioids decrease the brain’s awareness of the pain whereas the non-opioids affect some of the chemical changes that normally take place wherever body tissues are injured or inflamed.

Although non-opioids are often preferred for certain types of chronic pain, they have two serious drawbacks.  The first is the ceiling effect; Non-opioids have an upper limit of pain relief that can be achieved.  Once the upper limit is achieved; increasing the dosage will not provide any further pain relief but may exacerbate side effects.  Opioids on the other hand tend not to have a ceiling.  The more you take, the more pain relief you will get.  The second major drawback of non-opioids is the side effects profile.  The side effects of NSAIDS make it impossible for certain patient populations to use NSAIDs such as those with history of peptic ulcer disease, cardiovascular disease and the elderly. In 2014, the American Academy of Neurology determined that the risks of opioids outweigh the benefits for certain chronic pain conditions.

Treatment of pain with the use of medical foods gives patients a safer option for pain management by approaching pain from a new perspective.  Medical foods treat the nutritional deficiencies that are found in patients with acute and chronic pain.  By restoring an optimal balance between the chemicals in the body, substances called neurotransmitters, that are responsible for transmitting and dampening pain signals, one can better manage pain.

Research has found low levels of the amino acids gluatamate, tryptophan, arginine, serine, and histidine in patients with chronic and acute pain.  The perception of pain can be modified by providing amino acids and nutrient precursors to the key neurotransmitters involved in the pain process. Amino acids are able to cross the blood brain barrier and are necessary to produce the appropriate neurotransmitters needed to reduce pain signals and lower inflammation. Increasing the intake of amino acids and nutrients lead to an increase in neurotransmitter levels [1].

The theory that the body’s need for amino acids and nutrients are modified by a disease has been long recognized and is supported by studies that reflect changes in plasma, urinary and tissue levels of nutrients with modified intakes of these nutrients [2].   There are various reasons for depletion of nutrient levels including diet, metabolic demands and genetics.  The required amount for each patient varies depending on the duration and severity of pain. Addressing the increased demand for amino acids and nutrients is a key component for improving clinical outcomes.

Two double-blind clinical trials compared Theramine, a medical food specially designed to address the increased amino acid and nutrient requirements of pain syndromes, to low dose naproxen and ibuprofen.  In both studies, Theramine showed statistically greater pain relief than either naproxen or ibuprofen.  This was measured by patient report and a reduction in the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) [3, 4].  Treatment with amino acid precursors was associated with substantial improvement in chronic back pain and a reduction in inflammation.

Pain Reduction with TheramineThe improvement in pain directly correlated with increased amino acid precursors to neurotransmitters in the blood.

Theramine is designed using Targeted Cellular Technology (TCT), which facilitates the uptake and utilization of the neurotransmitters precursors that are used in the modulation of pain.  TCT allows for the production of neurotransmitters from ingestion of smaller amounts of amino acids to elicit the same response as larger amounts, making daily dosing more feasible and reducing the potential for tolerance.

At least 100 million adult Americans suffers from chronic pain, a safe and effective treatment option such as medical foods that do not treat symptoms alone but addresses the distinctive nutritional needs of adults who have different or altered physiologic requirements due to pain is vitally needed.

To date, Theramine has been in clinical use for over 10 years with no report of GI bleed or adverse side effects and the clinical trials of Theramine clearly support the theory that the nutritional management of pain syndromes is a safe and effective treatment for pain.

The Dangers of NSAIDs

The most commonly prescribed drugs for pain are Non-Steroidal Anti-Inflammatory drugs (NSAIDs).  Approximately 98 million prescriptions for NSAIDs were filled in the United States in 2012 [IMS 2012] and this number does not include NSAIDs that are purchased over the counter.  Although effective in treating pain and inflammation, NSAIDs are linked to adverse side effects which make them inappropriate for use in many patient populations.  There are several serious side effects and toxicity related to use of traditional NSAIDs. Toxic side effects of traditional NSAIDs include:

  • Stomach ulceration and/or bleeding
  • Kidney damage
  • Easy bruising because of loss of platelet function
  • Exacerbation of cardiovascular conditions

Recent studies have also highlighted a higher risk of atrial fibrillation with NSAID use [1] and an increase risk of bleeding and events such as heart attack, stroke or cardiovascular death with the use of NSAIDs in conjunction with antithrombotic therapy [2].

NSAIDs work to reduce pain and inflammation by inhibiting cyclooxygenase, an enzyme.  The action of inhibiting cyclooxygenases, reduces pain and inflammation but is also responsible for many of the side effects of NSAIDs.  This inhibition is problematic because it also inhibits some important functions such as the repair and maintenance of the stomach lining.  This is why stomach ulceration and irritation is so common with the use of NSAIDs.

Inhibition of cyclooxygenase is also associated with reductions in prostaglandin synthesis and is associated with less sodium being excreted in urine and constriction of blood vessels.  This effect of NSAIDs on blood pressure may increase mean arterial pressure by as much as 5 to 6 mm Hg in hypertensive patients.   This consequence may be of particular relevance in patients with preexisting hypertension, edema or congestive heart failure.

One study noted the rate of new-onset hypertension developing in elderly patients for whom nonselective NSAIDs were prescribed was 27% [3]

The extremely high risk of side effects with such commonly used medication resulted in a quest for an analgesic/anti-inflammatory that could provide therapeutic efficacy equivalent to that of traditional NSAIDs but without the gastrotoxicity.

The use of medical foods to treat the dietary deficiencies associated with pain and inflammation has proven to be a safe and effective method for pain control.  Two double-blind, randomized,  trials, which compared Theramine to low dose naproxen and ibuprofen demonstrated statistically significantly reduction in inflammation as measured by inflammatory markers, CRP and IL-6 as well as improvement in low back pain.  Theramine was shown to be an effective pain medication but also an effective anti-inflammatory agent without the risk of gastrointestinal bleeding or other serious side effects.

All of the ingredients in Theramine are GRAS (generally recognized as safe) products and carries no risk of addiction or attenuation.  Theramine has been on the market for 10 years without report of GI bleed or serious adverse side effects.

There are several patient populations that should avoid NSAIDs due to the high risk of side effects.

  • Patients over 65 years of age
  • Previous GI history such as peptic ulcers or previous GI bleed
  • Patients with cardiovascular disease
  • Patients with liver disease
  • Patients with kidney disease
  • Patients on anti-coagulants or low dose aspirin

The cumulative evidence of the danger of NSAIDs is an important reminder that the while NSAIDs can be helpful and at times necessary medications for satisfactory quality of life, use of these medications, particularly among high risk patients must be carefully considered.

 

1.  Gang Liu, MD, PhD, Yu-Peng Yan, MD, Xin-Xin Zheng, MD, Phd, Yan-Lu Xu, MD, Phd, Jie Lu, MD, Ru-Tai Hui, MD, Phd, Xiao-Hong Huang, MD, Phd “Meta-Analysis of Nonsteroidal Anti-Inflammatory Drug Use and Risk of Atrial Fibrillation” The American Journal of Cardiology Nov. 15, 2014 Vol. 114, Iss. 10

2. Anne-Marie Schjerning Olsen, Gunnar H. Gislason, Patricia McGettigan, Emil Fosbøl, Rikke Sørensen, Morten Lock Hansen, Lars Køber, Christian Torp-Pedersen, Morten Lamberts. Association of NSAID Use With Risk of Bleeding and Cardiovascular Events in Patients Receiving Antithrombotic Therapy After Myocardial Infarction. JAMA, 2015; 313 (8): 805

3.  Solomon DH, Schneeweiss S, Levin R, Avorn J. “Relationship between COX-2 specific inhibitors and hypertension” Hypertension. 2004; 44: 140–145

Alternatives to Opioid Pain Medications for Injured Workers

Workplace injuries affect approximately 4.1 million Americans annually (1) .  More than half of these injured individuals will have to miss work and receive long-term medical care.  Worker’s compensation plans provide partial wages during the time of injury and recovery period in addition to covering the cost of medical care.  The recent trend among physicians treating work related injuries has been the practice of prescribing high and sometimes dangerous doses of opioid pain medications for extended periods of time.  Data from 2005-2008 in 17 states showed an average number of 1,599 cases requiring narcotics for non-surgical cases, with more than seven work days missed due to injury(2).  Additionally, in an average of 6% of these cases, the narcotics were prescribed for long-term periods of time.  These drugs may include but are not limited to hydrocodone, fentanyl, methadone, and oxycodone.  Approximately 50-90% of injured workers will receive narcotics for chronic pain conditions (3).  Opioid pain medications can have deadly side effects and the increased availability and dosages of these medications can be detrimental to an injured worker and prolong the time it takes to return to work.

Opioid pain medications are the most commonly prescribed medication in the United States(4).  They work to decrease the perception of pain and increase pain threshold.  While these drugs are helpful to decrease overall pain of various injuries and conditions, they are highly addictive and only address a portion of the pain process.  Common side effects may be mild such as constipation and fatigue, however, they have also been linked to more severe side effects including sleep apnea, decreased hormone production, and increased falls and broken bones among the elderly population(4).  Additionally patients taking opioid pain medications for long periods of time can become addicted and experience serious symptoms of withdrawal which include nausea, shaking, chills, and sweating when finishing a course of these medications (5).  Lately there has also been in an increase in drug overdose leading to death.  In a study that observed 10,000 patients who were prescribed opioids for 90 days, 51% experienced at least one overdose, and six individuals died as a result of overdose 6.  In 2008 the number of deaths resulting from overdose reached nearly 15,000 individuals(1).

Increased availability and access to opioid pain medications is one of the main problems leading to addiction and overdose among injured workers.  Some physicians are prescribing these medications to treat acute and long-term pain disorders such as arthritis and musculoskeletal pain.  Oftentimes high doses are prescribed and the dosage continues to increase over time as tolerance to the effects of the medications increases.  Instead of treating the underlying physiological conditions causing the painful condition, opioid pain medications are prescribed to help manage and mask the pain associated with a work related injury. They are prescribed for many reasons, however, a few of the most common are pressure from patients to prescribe a strong medication that will lead to decreased pain, as well as pressure from insurance companies to prescribe the most cost-effective generic pain medications. Patients may experience temporary pain relief while on these medications, however chronic pain may persist long after the injury has healed.

Prescribing high dose opioid pain medications for work related injuries often leads to other injuries and physiologic impairments.  In many cases, patients remain out of work for much longer than individuals who are not prescribed opioids, as they often develop new health conditions and require more medications.  In the study conducted by the Danish Health Interview Survey in 2000 observing 10,434 individuals, patients who were not prescribed opioid pain medications to treat their injuries recovered four times more often than individuals prescribed opioid pain medications(7).  Additionally, in this study patients taking opioid pain medications were shown to have a lower quality of life and higher death risk than those patients managing pain without opioids.

Some patients who are prescribed opioid pain medications, especially long-term, may develop other serious conditions such as obesity, mood disorders, and depression.  An injured worker who is taking medication for a pain condition may not be able to exercise regularly and weight gain is fairly common.  Opioid pain medications can also have an effect on overall mood and quality of life.  If an individual takes these medications long-term it can be very hard to stop taking them.  The patient can experience large amounts of anxiety and depression when decreasing the dosage or attempting to discontinue the medication all together.  Research has found that of the 1.9 million workers claims that were filed between 2007-2008, those who previously had or developed a co-morbidity as a result of injury such as depression, obesity, or hypertension, experienced more costly treatments and often longer treatment plans all together(8).

Work related injuries will continue to be an issue for insurers and employers.  The overprescribing of opioid pain medications in this country must be addressed by physicians, insurance companies, and drug manufacturers.   The conversion of acute pain to chronic pain associated with a work related injury can be managed in a more efficient way that will allow an injured worker to return to work as soon as they are healed without the burden of addiction or other opioid pain medication related side effects.  Theramine can be used as a complimentary or standalone therapy among this vulnerable population and can provide treating physicians with the ability to prescribe the lowest effective dose of an opioid pain medication while addressing the underlying pathology of the pain process.

Theramine is a prescription only medication regulated by the FDA as a medical food. Medical foods are prescription only medications which address the underlying pathology of pain associated with the work related injury or illness.  Theramine is clinically proven to correct amino acid deficiencies associated with chronic pain syndromes, and improve the overall perception of pain(9).  Theramine is designed to manage the increased nutritional requirements associated with acute or chronic pain conditions.  Theramine is a proprietary amino acid formulation that, by providing neurotransmitter precursors, helps stimulate production of neurotransmitters that are often deficient in pain conditions.  The ingredients in Theramine are Generally Recognized as Safe by the FDA, and are specially formulated utilizing a proprietary Targeted Cellular Technology to facilitate the uptake and metabolizing of milligram quantities of amino acids and other nutrients.  There have been no reported adverse side effects associated with the clinical application of over 50 million individual doses of Theramine. The most common side effects associated with amino acid therapies are headache, dry mouth, and upset stomach and are often short term, and can be decreased with increased fluid intake.  Theramine can be administered in conjunction with the lowest effective doses of an opiate or NSAID pain medication without loss of efficacy(10).  Treating work related injuries with Theramine may prove to be one possible medication solution to control pain and help decrease the quantity and dosages of opioid pain medications administered in the United States.

1)      http://www.workers-comp-news.com/injury_stats.php

2)      http://www.wcrinet.org/studies/public/books/WCRI_2012_Annual_Report.pdf

3)      http://ehstoday.com/health/workers-compensation/injured-workers-opiate-addiction-0209/

4)      http://www.nytimes.com/2012/04/09/health/opioid-painkiller-prescriptions-pose-danger-without-oversight.html?pagewanted=all

5)      http://www.opiates.com/opiate-withdrawal.html

6)      http://www.crcotp.com/crcotp_featured/even-when-prescribed-opioids-can-cause-addiction-and-overdose.php

7)      A Population-based Cohort Study on Chronic Pain:The Role of Opioids Per Sjøgren, MD, DMSC,* Morten Grønbæk, PhD, Vera Peuckmann, PhD,  and Ola Ekh-+olm, PhDw, Lippincott Williams & Wilkins, 2010.

8)      http://coventrywcs.com/web/groups/public/@cvty_workerscomp_coventrywcs/documents/webcontent/c054910.pdf

9)      Shell WE, Silver D, Charuvastra E, Pavlik S, Bullias D; “Theramine and Ibuprofen for the treatment of chronic low back pain double blind clinical trial”, 2010 Targeted Medical Pharma Inc.

10)   Shell WE et al.; “Theramine and Naproxen for the treatment of low back pain, a double bind clinical trial”; Americal Journal of Therapeutics April,2012.

Pain Management in Lyme Disease

Lyme disease is spread through the bite of infected blacklegged ticks, also known as deer ticks.  Ticks can attach to any part of the human body, but tend to reach areas that are difficult to see such as the groin, armpits, or scalp.  Ticks must be attached for 36 hours or more before the Lyme disease bacterium, Borrelia burgdorferi, can be transmitted.

There are four stages in the progression of Lyme disease.  The first stage, known as the early localized stage, takes place between 3-30 days after the tick bite.  The infected person can experience fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes.  One of the most prominent signs of this stage is the Erythema migrans rash, also known as the bull’s-eye rash for its unique shape.  This rash occurs in 60% of infected individuals. (CDC)

The second stage is known as the early disseminated stage and it occurs days to a week after the tick bite if the bite is not treated within the early localized stage.  During this stage, a person starts to experience more noticeable and serious symptoms.  These symptoms include Facial or Bell’s palsy, additional erythema migrans rashes, and stiffness due to meningitis.  At this point, patients begin to feel shooting pains that can interfere with sleep as well as pain and swelling in the large joints.

If the disease is not treated, 60% of patients enter into the late disseminated stage which happens months to years post-tick bite.  These individuals typically develop arthritis with severe pain and swelling in the joints.  It is typically found in the larger joints, for example the knees.  Arthritis caused by Lyme disease exhibits itself differently than other causes of arthritis.  Lyme arthritis is similar to osteoarthritis because of stiffness due to painful swollen joints.  This happens because Lyme bacteria invade the joints and cause inflammation to the tissue that lines the joints, and eventually, if untreated, can cause the cartilage within the joints to become damaged.[1]

The final stage is the lingering symptoms after treatment.  About 10-20% of patients experience symptoms after the patient has taken antibiotics.  This is called Post-treatment Lyme disease syndrome (PTLDS).  Some evidence shows this is due to an autoimmune response, in which the immune system is continuing to respond after the infection has been cleared, causing damage to be done to a body’s tissues.  Symptoms of PTLDS can include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. (CDC)

The quicker a doctor is able to diagnose Lyme disease, the quicker they can treat it.  Patients can be prescribed antibiotics in order to rid their system of the bacteria.  Most patients who are prescribed the antibiotic during the early stages usually recover quickly and completely.

With the antibiotics working to take care of the bacteria, what is taking care of the pain associated with Lyme disease?  A patient can still be experiencing pain while taking these antibiotics, which progressively becomes worse throughout all the stages Lyme disease.  Patients who experience pain in association with Lyme disease are less likely to be active, sleep well, or eat properly due to pain.

Commonly prescribed pain medications are opioids and NSAIDs.  Both, although common, can be very dangerous.  According to a report released by the National Institute on Drug Abuse, there can be consequences when choosing to use an opioid.  Opioids are easy to abuse because of their addictive qualities.  Regular or long term use of opioids can lead to physical dependence and addiction. Once a patient stops using opioids, they can experience withdrawal symptoms such as restlessness, muscle and bone pain, insomnia, diarrhea, vomiting, cold flashes with goose bumps, and involuntary leg movements.  An overdose can cause severe respiratory depression and death. [2]

NSAIDs, although effective in treating pain and inflammation, are linked to adverse side effects which make them inappropriate for use in many patient populations.  There are several serious side effects and toxicity related to use of traditional NSAIDs which can lead to costly hospitalizations or death.  A study on the effects of NSAID induced side effects in the elderly reflected the average direct costs of GI side effects per patient-day on NSAIDs were 3.5 times higher than those of a patient-day not on NSAIDs. Seventy percent of the cost was attributed to GI events resulting from NSAID treatment.[3]  Treatment of GI problems alone caused by the use of NSAIDs is estimated to add over 40% to the cost of arthritis care.[4]

Stephen Harrod Buhner’s book “Healing Lyme Disease Coinfections” discusses an alternative to these common pain medications called Theramine®. Theramine is a medical food specifically designed for the dietary management of pain syndromes. This specialized natural product, provides the specific amino acids and nutrients required by the brain and nervous system to effectively reduce pain and inflammation. Theramine is non-addictive and is not associated with adverse GI or cardiovascular side effects.  It is used in clinical practice to reduce inflammation and improve pain perception by addressing the increased nutritional requirements of pain syndromes.  In two double blind, multi-center clinical studies comparing Theramine and an NSAID, Theramine was shown to be more effective at treating pain and inflammation than either naproxen or ibuprofen. Lyme disease can alter the metabolic requirements of the body, leading to specific amino acid and nutrient deficiencies. Effectively managing the increased demand for these essential physiologic components should be an integral part of any pain management protocol.

 


[1] American Academy of Orthopaedic Surgeons. “Effective treatment of Lyme-disease-related arthritis depends on proper diagnosis.” ScienceDaily. ScienceDaily, 2 February 2011.

<www.sciencedaily.com/releases/2011/02/110202132605.htm>.

[2] “Prescription Drugs: Abuse and Addiction” NIDA. October 2011. National Institute on Drug Abuse.

[3] Br J Clin Pharmacol. 2001 August; 52(2): 185–192. Cost of prescribed NSAID-related gastrointestinal adverse events in elderly patients

[4] Bloom, BS. Direct medical costs of disease and gastrointestinal side effects during treatment for arthritis. Am J Med. 1988; 84(2A): 20-24