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

The Problem with Prescription Pain Killers

Pain is a big deal. On one level, it’s very useful. It tells us when there’s something wrong, and is pretty efficient at giving us a handy indication when what we’re doing may not be particularly good for us. Those who cannot feel pain [1] suffer from horrendous associated problems, and frequently damage themselves quite badly without being alerted to the fact that they’re doing so by pain. However, unlike a man-made alarm, the body does not come with an ‘off’ switch which one can hit once one’s been made aware of the problem. Chronic pain is a major issue, and one of the most troubling symptoms of a great many medical conditions. It’s a factor which seriously affects people’s lives, and good pain management is recognized as being vital to the all-important quality of life [2] experienced by those needing medical treatment. Having said this, however, it is also being increasingly recognized that the people of North America are becoming dangerously dependent upon prescription painkillers. All too often, we pop a pill when we do not really need to, and plenty of us are relying on prescribed narcotic painkillers when we would undoubtedly be a lot better off with some other method of pain-relief. While there is certainly a place for narcotic painkillers in the management of seriously painful conditions, it needs to be recognized that these drugs do come with a major health warning – and alternatives or avoidance should be the preferred options if at all possible.

Narcotic Painkillers

Opioid painkillers were originally designed for cancer pain and somehow over time have become a first line therapy for many physicians despite the potential for addiction. What may be lesser known, however, are the dangers inherent within these drugs, and the startling scope of America’s dependence upon them. Put simply, opioids such as Vicodin and codeine bind to opioid receptors within the brain, which dulls the brain’s pain response. These receptors are designed to work with the body’s natural opioids – endorphins [3]. Endorphins are released during exercise, and numb pain as well as promoting a feeling of wellbeing, enabling and motivating us to stay on the move and thus potentially to survive for longer. Narcotics fulfil the same role – but in hyper-exaggerated form. Narcotic analgesics swamp our opioid receptors, saturate them to the point where we’re utterly numbed and frequently rather high. They’re very effective as a method of pain relief, but also quite dangerous and are associated with a host of dangerous side effects.

Painkiller Addiction

It’s very easy to develop a taste for opioid painkillers. Why wouldn’t you? They keep pain at bay, and they make you feel good. They’re also, unfortunately, highly addictive. Their very nature means that you’re inclined to seek out more and more – and America’s healthcare system doesn’t exactly discourage you from overdoing it. Big pharmaceutical companies do, after all, stand to make a lot of money from plenty of pill-popping patients. North America has the world’s worst rate of prescription painkiller addiction by a long, long way [4]. Places with nationalized healthcare (in which pharmaceutical companies would have nothing to gain from touting their product to the public) are not in any more pain than the people of America, but they’re far less addicted to painkillers. The solution for someone from the USA to the slightest malady invariably involves popping a pill, while those from other countries are put on courses of pills only when necessary, and given alternative pain-relief methods more often. Each system obviously has its pros and cons – but in this particular case the figures concerning painkiller addiction speak for themselves. More overdose deaths in the USA have been caused by prescription narcotics since 2003 than cocaine and heroin put together – partly (if not wholly) because narcotic prescription rates have increased enormously in this time [5].

An Easy Death

A major issue with opioid painkillers is that they’re not only all too easy to get hold of, and highly addictive – they’re also unpredictable killers. While medical science is pretty good at estimating doses according to body weight and so on, the problem of tolerance is always going to rear its ugly head. The body develops a resistance to opioids over time which means that one must take a higher and higher dose in order to achieve the desired effect. And, at any moment, that dose might prove just too high for the body to cope with. Opioids kill in a number of ways. The most common of these is respiratory depression. This can be reversed – but only if the overdose is low and medical aid arrives quickly [6]. If this is not the case, then the overdoser finds themselves unable to adequately fill their lungs and essentially starves of oxygen. It is far better not to risk this, not to get addicted, and to seek alternatives to narcotic analgesics whenever possible!

[1] Gillian Mahoney, “Meet the Child Who Feels No Pain”, ABC, Oct 2013

[2] Nathanial Katz, “The Impact of Pain Management on Quality Of Life”, Journal of Pain and Symptom Management, Jul 2002

[3] PBS, “Role of endorphins discovered, 1975”

[4] Arnold M. Washington, “America’s Painful Love Affair With Painkillers”, Rehabs

[5] National Safety Council, “Opioid painkillers: How they work and why they can be risky”

[6] Ben Wolford, “Respiratory Depression Reversed In Trials With Drug That Fights Opioid Side Effect”, Medical Daily, Aug 2014

 

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

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