Is Your OTC Pain Reliever Going to Kill You?

Although acetaminophen (Tylenol) is heavily marketed for its safety, FDA recommends health care professionals to discontinue prescribing and dispensing drug products with more than 325 mg of acetaminophen due to the high risk of liver injury.  Severe liver injury may occur in patients who:

  • Took more than the prescribed dose of an acetaminophen containing product in a 24 hour period.
  • Took more than one acetaminophen containing product at the same time.
  • Drank alcohol while taking acetaminophen products.

Acetaminophen is widely used as an over the counter pain reliever and fever medication and is often combined with other ingredients such as cough and cold ingredients.  Patients may be unaware that many products (both prescription and OTC) may contain acetaminophen, making it easy to accidentally take too much [1-5]. In fact,  acetaminophen poisoning accounts for approximately one-half of all cases of acute liver failure in the United States and Great Britain[16].

Ibuprofen (Motrin, Advil) is also widely used for pain and inflammation but not without risk.  Ibuprofen carries a black box warning from the FDA regarding the cardiovascular and gastrointestinal risks associated with its use.  Patients taking ibuprofen have an increased risk of serious cardiovascular thrombotic events including myocardial infarction and stroke. Researchers in Denmark observed a nearly threefold increase in the number of deaths from gastrointestinal bleeding within one year of ibuprofen prescription [14].  The risk of side effects is so high for elderly patients the American Geriatrics Society has recommended that patients over the age of 65 avoid NSAID use if at all possible [6-10].  This real risk was studied by RE Tarone who noted a marked rise in baseline rate of gastrointestinal bleed with advancing age with the large majority of cases occurring among persons age 65 or older.  The average relative increase in risk of gastrointestinal bleeding was found to be fourfold or slightly higher in NSAID users and six fold or higher at heavy prescription levels [15].

NSAID High Risk Groups

Medications such as Tylenol and ibuprofen, which are readily available over-the-counter, are perceived to be safe medications; but research has proven that they are not without risk.  Physicians, payers and patients are requesting a safe more effective alternative to treat pain which becomes increasingly important as the population ages.

Medical foods such as Theramine treat the dietary deficiencies that are associated with pain and inflammation.  Pain reduction is accomplished by moderating responsiveness to noxious stimuli, regulating the transmission of pain signals and controlling inflammation. The use of medical foods has been long standing and there have been no reports of GI bleed in over 10 years on the market.

Two multi-center double-blind clinical trials established the safety and efficacy of Theramine in the treatment of chronic back pain.  In a clinical study comparing the medical food Theramine and a non-steroidal anti-inflammatory medication, Theramine was shown to be more effective than low dose NSAIDs in treating low back pain.  Clinical data indicate significant reduction in back pain with the administration of Theramine alone, while administration of a low dose NSAID had no appreciable effect on pain.

An important observation by researchers EL Fosbol and L Kober note that, “Individual NSAIDs have different cardiovascular safety that needs to be considered when choosing appropriate treatment.  In particular, rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals.  This notion is also valid for healthy individuals and underlines the importance of critical use of NSAID therapy in the general population and also that over-the-counter retail of NSAIDs should be reassessed.”[13]

 

REFERENCES

 

1.  Wolf M; King J; Jacobson K; et al “Risk of Unintentional Overdose with Non-prescription Acetaminophen Products”  J Gen Intern Med 2012 Dec; 27(12): 1587-1593

2.  “Acetaminophen Toxicity in Children” Pediatrics vol. 108 No. 4 Oct. 1 2001

3.  Farrell S; Tarabar A; et al “Acetaminophen Toxicity” Medscape June 24, 2011

4.  Plaisance K “Toxicities of Drugs Used in the Management of Fever” Clinical Infectious Diseases 2000 31 Supp 5: S219-S223

5.http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm381650.htm

6.http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm085282.htm

7.  Pilotto A; Franceschi M; Leandro G; Di Mario F; “NSAID and aspirin use by the elderly in general practice:  effect on gastrointestinal symptoms and therapies:  Drugs Aging 2003; 20(9): 701-10.

8.  Smith SG “Dangers of Non-steroidal Anti-inflammatory drugs in the elderly” Can Fam Physician vol. 35 March 1989

9.  American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults

10.  Gurwitz JH; Everitt DE; Monane M; Glynn RJ, Choodnovskiy I; Beaudet MP; Avorn J; “The impact of ibuprofen on the efficacy of antihypertensive treatment with  hydrochlorothiazide in elderly persons” J Gerontol A Biol Sci Med Sci 1996 Mar; 51 (2): M74-9

11.  Shell WE; Charuvastra E; DeWood M; May L; Bullias D; Silver D “ A Double-blind controlled trial of a single dose naproxen and an amino acid medical food Theramine for the treatment of low back pain”  Am J of Ther 2010

12.  Shell WE; Pavlik S; Roth B; Silver M; Breitstein M; May L; Silver D “ Reduction in pain and inflammation associated with chronic low back pain with the use of the medical food Theramine”  Amer J of Ther 2014

13.  Fosbol EL; Kober L; Torp-Pedersen C; Gialason GH “ Cardiovascular safety of non-steroidal anti-inflammatory drugs among healthy individuals”  Expert Opin Drug Saf 2010 Nov; 9(6): 893-903

14.  Lipworth L; Friis S; Blot Wj; McLaughlin JK; Mellemkjaer L; Johnsen SP; Norgaard B Olsen JH “ A population based cohort study of mortality among users of ibuprofen in Denmark”  Am J Ther 2004 May-Jun; 11(3): 156-63

15.  Tarone RE; Blot WJ; McLaughlin JK “Nonselective non-aspirin non-steroidal anti-inflammatory drugs and gastrointestinal bleeding:  relative and absolute risk estimates from recent epidemiologic studies”  Am J Ther 2004 Jan-Feb; 11(1): 17-25

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.

A New Approach to Improving Neuropathic Pain

In the United States, approximately 20 million people suffer from neuropathy. The most common form of neuropathy is diabetic neuropathy with over half of diabetes patients living with this condition. Neuropathy may also be caused by poor circulation, herpes outbreaks or can be drug induced.

Neuropathic pain is the result of degeneration of the outer sheathing or myelin sheath of nerve cells. This is analogous to an electrical wire that is covered with insulation, and the insulation is beginning to breakdown. Without insulation the unprotected wire will start short-circuiting. In the same way, when the sheathing of nerve cells degenerate, the signals being transmitted start to  misfire, resulting in the body receiving signals that are interpreted as numbness, heat, cold, tingling and pain in the toes, feet legs, fingers, hands and arms.

Degradation of the myelin sheath results in unusual sensitivity of the neurons and abnormal excitability and heightened sensitivity to stimuli, also known as peripheral sensitization. The heightened sensitivity results in an increased demand and competition for nutrients involved with the pain receptors, particularly arginine, choline, GABA, glutamine, histidine, and serine.

The degradation of nerve pathways increases the turnover rate of the precursors needed for neurotransmitter function.  This results in a reduction in the level of production of neurotransmitters. The nutritional requirements for proper neurotransmitter function are such that they cannot be achieved by the modification of diet alone.

Unfortunately, current neuropathy treatment exists primarily of palliative treatment of symptoms. There are a variety of treatments available that range from pharmaceutical drugs and creams to therapies that stimulate the nervous system.  Antidepressants, especially tricyclics and selective serotonin-norepinephrine re-uptake inhibitors (SNRI’s), have been mainstay treatments for neuropathic pain along with antiepileptic drugs such as Lyrica and Neurontin. Opioid narcotic treatments for neuropathy are used as well but are less favored because of the risk of dependency. Most topical treatments have been largely ineffective at improving symptoms or the disease.

Treatment that addresses the distinctive nutritional needs of adults suffering from neuropathic pain rather than treating symptoms alone is a rapidly expanding field of interest for podiatric medicine.  The unique nutritional needs that arise in patients suffering from neuropathic pain cannot be satisfied through a conventional diet or through supplementation (i.e., use of a dietary supplement).

An open-label pilot study of an amino acid-based oral formulation was shown to reduce symptoms of pain and numbness related to peripheral neuropathy by supplying amino acids and other dietary factors which support induction, maintenance, and enhancement of the specific neurotransmitters involved in pain. Use of neurotransmitter precursors in a patented Targeted Cellular Technology system allows for smaller amounts of amino acids to be rapidly utilized by target cells making daily dosing more feasible and efficient.  Supplying the nutrients involved with the various pain signaling pathways in a targeted delivery system  can synchronize the availability of the precursor supply with the fluctuating demand for the corresponding neurotransmitters resulting in reduced pain, inflammation and numbness.

Neuropathic pain may not be completely preventable. Controlling blood sugar levels if you have diabetes, smoking cessation, alcohol moderation and regular exercise can help. In many cases a prescription nutrition program that addresses the increased requirements of the disease is needed for optimal clinical results and increased patient satisfaction.