Pain Medication: Risks and Alternatives

Paul L. Reller L.Ac. / Last Updated: August 03, 2017


Understanding of the safe and unsafe levels of acetaminophen (paracetamol)

Today, almost all narcotic pain medications contain more, or an equal amount of, acetaminophen than the FDA Advisory Panel found to be a safe maximum in 1997, and the number of over-the-counter pain relievers in drugstores with at least 325 milligrams of acetaminophen has increased greatly. The public is not aware of what they are taking, or the risks and unseen damage. The array of brand names with high dosage acetaminophen, and combinations of other drugs with acetaminophen is now incredible, and many patients suffering from chronic pain take more than one medication with acetaminophen included in the drug, making the occurence of overdosage of acetaminophen extremely high. In 2002, the FDA Advisory Committee estimated that up to 74 percent of overdosage ingestions were unintentional, meaning that either doctors had prescribed the overdosage, or patients had intentionally, although unaware of the risks, self-medicated with too high a dosage. In 2014, the U.S. FDA responded to the 2011 call to limit dosage of acetaminophen in pain medications by issuing and "urging" to pharmaceutical companies, showing just who was in charge (sic). In 2015, experts at the University of Sydney School of Medicine, in Australia, published a meta-review of all high-quality randomized controlled human clinical trials of acetaminophen (paracetamol) that finally showed that this ubiquitous pain medication did not relieve pain better than placebo for low back and neck pain, and showed only small effect over placebo for osteoarthritis of the hip and knee (see study link in Additional Information). They also noted evidence of common association with adverse effects on liver function with chronic use, and other adverse health effects. Despite the late study of effectiveness that contradicts decades of assumed proof there is still no actual regulation or public education to stop the amazing amount of injury from excess acetaminophen use each year.

The brand names of acetaminophen (paracetamol) include Anacin-3, Bromo Seltzer, Pediacare Children's Fever Reducer Pain Reliever, Pediapap, Tylenol, and many others, including combinations of acetaminophen (paracetamol) with other chemicals in Actifed, Alka-Seltzer Cold and Sinus (and most Alka-Seltzer medications), Allerest Sinus, Anacin-PM, Bayer Select, Benadryl Allergy Cold, Comtrex Cold and Flu, Contact Cold and Flu, DayQuil Cold and Flu, Dimetapp Cold and Flu, Dristan Cold and Flu, Endocet, Excedrin Aspirin-free, Flextra, Midol Maximum Strength Menstrual, Midol Teen, Nyquil Cold and Flu, Robitussin Cold Cough and Flu, Sinarest, Sominex Pain Relief, Sudafed Sinus, Theraflu, and many other brand names. At this point in time, many patients are unwittingly taking acetaminophen in a number of forms daily, exceeding the safe dosage, and creating toxicity, in many cases. When combined with pain-relieving narcotic pain meds, the potential for acetaminophen toxicity is high. The affects of acetaminophen toxicity are usually not apparent immediately, but insidious, and can be a cause or contributor to many common health problems over time. Use of acetaminophen that follows the guidelines of care, limiting the daily dosage and using the drug only for short term relief, not chronic use in multiple forms, is of course safe. Patient awareness of these safety guidelines, and the other sensible means to relieve pain, and actually cure the underlying causes of pain, with Complementary and Integrative Medicine and Traditional Chinese Medicine (CIM/TCM) is very important.

The most common prescription pain relievers with a high dosage of acetaminophen are Hydrocodone and Oxycodone, usually known by the trade brand names as Vicodin, Norco, and Percocet. 'Oxy' is now a familiar street term as well, as it has perhaps become the most abused street drug today in the United States. Our teenage children do not realize that they are damaging their livers, and the array of negative health problems in the future from this drug abuse will be incredible. In comparison, the use of simple heroin has few actual negative health effects other than the threat of overdose death. In 2002, strict warnings were routinely issued by medical doctors to not exceed dosage recommendations with Vicodin, or other forms of Hydrocodone, a synthetic form of codeine. One Vicodin tablet may contain up to 750 milligrams of acetaminophen. Doctors advised that there was a serious risk of overdose if patients took more than one or two of these higher dosage Hydrocodone and acetaminophen combinations. This taking of 2 pills, which was common, would means that the patient was taking 1500 milligrams of acetaminophen with one dose! Percocets, or other forms of Oxycodone, could contain up to 650 milligrams of acetaminophen. Drug companies told the prescribing doctors that patients should try not to exceed 4000 milligrams per day of acetaminophen! The reality of chronic pain is well known, though. These synthetic opioid medications have a very diminished effect with over 10 days of use. Chronic pain sufferers would resort to increasing dosages over time. After some time of use, it is believed that the high dosage of acetaminophen is probably the most effective part of the medication. Liver damage is expected, and the array of health problems associated with chronic liver dysfunction is dizzying. Of course, we all just ignore this fact, doctors and patient alike.

So let us do the math. The Merck Manual states that 7500 mg per day in a typical adult (not a small person) will result in acute liver toxicity, or acetaminophen poisoning. Now, with taking just 2 high dose Vicodans at a time, every 2-3 hours, at 1500 mg of acetaminophen per dose, a person with moderate chronic pain taking 5 doses per day is consuming what the Merck Manual states is acetaminophen toxic dosage for acute liver damage and serious consequences! Obviously, many patients were taking at least this amount, and many of these patients were smaller in stature, or had other contributing factors impacting liver function. Of course, over time, with chronic pain medication use, the liver function is expected to be over-stressed and more susceptible to acetaminophen toxicity. The incredible fact is how the medical community, the government, and the public, especially those doing the deed, have remained so placid and unconcerned. We get so consumed by news of a natural disaster, terrorist attack, or common diseases, and yet a problem that is causing more deaths, and a lot more health injury, is treated so lightly. It could be that the pharmaceutical industry, with massive amounts of money spent on lobbying, advertising, payments to medical professionals and researchers, and domination of media advertising income, have succeeded in protecting the enormous profits reaped from this misguided treatment of chronic pain, and have thoroughly controlled public and professional perception, and enormously threatened public health, without consequence.

The response to the common overdosage of Vicodin, or other Hydrocodone prescription, with chronic untreated pain, led to the pharmaceutical industry heavily promoting another solution. Norco contains 10 mg of hydrocodone bitartrate, which is twice the dosage of standard Vicodin, but limits the amount of acetaminophen (paracetamol) to 350 mg per dose. Standard dosage often prescribes 2 Norco every 3 hours, though. A high dosage form of Vicodin, with 7.5 mg hydrocodone, was also made available, but this pill contains 750 mg of acetaminophen (paracetamol) per pill, and although dosage is not supposed to exceed 1 tablet per 3 hours and 5 maximum per day, chronic pain sufferers are well known to heavily exceed this dosage, and the reports of patients obtaining prescriptions from multiple doctors at once, or supplementing with illegally purchased hydrocodone (re: the Rush Limbaugh episode, where his housekeeper revealed that she was acting as Mr. Limbaugh's drug runner (or legal purchaser) for years, and Rush was found to be using as many as 30 Oxycontin per day, and utilizing perhaps 7 prescriptions, despite lack of evidence that he had a serious condition causing severe pain. His admittance of drug overuse pointed only to his pilonidal cyst, a hair follicle cyst near the anus, that is almost never left untreated with minor surgery when painful.) This example is only one of millions of chronic abuse of amazing overdose of narcotic pain medications with concurrent amounts of acetaminophen per day that is way beyond the maximum amount that the FDA Advisory Panel suggested came with high risk of liver damage in 1977.

The typical patient with chronic use of pain relieving medication, though, is not a drug abuser, but an ordinary person with a chronic pain, or subacute pain, that is not being treated properly, and instead "managed" with pain medications either prescribed, or obtained over-the-counter from the drugstore without need of prescription, or taking a combination of nonprescription and prescription pain medications. The increase in sales and prescription of pain medication in the last decade is quite dramatic in the U.S., and attracting concern from a number of quarters. Awareness of the consequences of this common type of pain relief is resulting in more and more patients in recent years exploring alternatives to pain managed, or masked, by drug use, and more and more turning to acupuncture and TCM medicine. A combination of acupuncture with physiotherapy (Tui na), herbal and nutrient medicine, correction of postural mechanics and habits that perpetuate tissue injury, and instruction in targeted stretch and exercise, provides an extremely effective alternative to these harmful practices of overconsumption of standard pain drugs.

Warnings of the associations between acetaminophen toxicity and the rising rates of asthma, COPD, allergic sinusitis/rhinitis and eczema, as well as developmental problems in infants with pregnant mothers using acetaminophen for more than 28 days of pregnancy

With health authorities speaking worldwide of a rise in the incidence of asthma, COPD, allergic sinusitis, and eczema over the last decade, many studies have been performed to determine the underlying causes of these now prevalent and serious disorders. Of all associations in large demographic studies of patient histories and potential causes, the increase in the use acetaminophen stands out. A 2014 meta-review of these studies at Brigham and Women's Hospital and Harvard Medical School also showed that acetaminophen and ibuprofen use in pregnancy, infancy and early childhood was clearly associated with increased asthma risk in childhood (PMID: 25441647).

Acetaminophen (paracetamol) is the non-steroidal anti-inflammatory (NSAID) medication most associated with asthma. Both asthma and allergic sinusitis (rhinitis), which is heavily associated with asthma, especially in young patients, have shown a significant association with acetaminophen use in large studies. A large study in 2010 by the University of Auckland, New Zealand, part of The International Study of Asthma and Allergies in Childhood (ISAAC), found that the most prevalent associations with prevalence of asthmatic symptoms worldwide were sales of acetaminophen (paracetamol), trans fats in food, and smoking prevalence in women (PMID: 20092649). Even air pollution, as measured by ambient particulate matter (PM), or soot, which has been blamed in recent years for increase in asthmatic symptoms, and generated bans on the use of fireplaces and wood stoves in cities such as San Francisco, was found to have little or no association with the prevalence of childhood asthma by the ISAAC study (PMID: 19819866). The increase in sales of acetaminophen were highly associated.

A 2011 report by the Akron Children's Hospital Department of Pediatrics, in Akron, Ohio, and published in the medical journal Pediatrics (2011 Dec:1181-5), stated that: "The epidemiologic association between acetaminophen use and asthma prevalence and severity in children and adults is well established. A variety of observations suggest that acetaminophen use has contributed to the recent increase in asthma prevalence in children: (1) the strength of association; (2) the consistency of association across age; (3) the dose-response relationship; (4) the timing of increased acetaminophen use and the asthma epidemic; (5) the relationship between per-capita sales of acetaminophen and asthma prevalence across countries; (6) the results of a double-blind trial of ibuprofen and acetaminophen for treatment of fever in asthmatic children; and (7) the biologically plausible mechanism of glutathione depletion in airway mucosa. Until future studies document the safety of this drug, children with asthma or at risk for asthma should avoid the use of acetaminophen." There can be no more certain statement than this.

One particular aspect of the link between acetaminophen use and asthma, as well as chronic allergic sinusitis and eczema, is the depletion of our most important cellular detoxification pathway, the glutathione depletion in airway mucosa. The subject of glutathione may be further explored on a separate article on this website, entitled Glutathione Metabolism, restoration and balance. Since 1999, the sales of acetaminophen have increased dramatically, and these red flags concerning the liver toxicity and damage to the detoxification pathway resulting from acetaminophen use were ignored, as the increase in asthma, COPD, allergic sinusitis and eczema have now reached epidemic proportions, according to health experts.

In 2013, experts at the University of Oslo, the Norwegian Institute of Public Health, and the Hospital for Sick Children in Toronto, Canada, examined data from over 3000 paired infants and found that children whose mothers used acetaminophen in pregnancy for more than 28 days of the pregnancy showed developmental impairment, with behavioral problems, poor communication skills, and poorer gross motor skills (see study link in Additional Information). Acetaminophen is the most widely used pain reliever used in pregnancy worldwide, either by itself, or within other medications. The rising rates of Attention Deficit and Hyperactivity Disorders could be partially attributed to rising use of acetaminophen in pregnancy, and this was treated with long-term use of amphetamine medications and anti-psychotic medications on a large scale, which itself is now proven to have caused many adverse effects in the short-term and later in life.

How Acetaminophen (paracetamol) damages the liver, and how to correct this damage with herbal and nutrient medicine and acupuncture

Acetaminophen, or paracetamol, is a drug that is broken down in the liver, and this detoxification process may overstress the liver, as well as produce harmful byproducts that are very toxic. One byproduct of acetaminophen catabolism is N-acetyl-p-benzoquinoneimine (NAPQI), which if produced in very small amounts in the liver is mostly excreted in the urine. Whenever there is an appreciable amount of NAPQI, though, liver cells are harmed by the toxicity. As acetaminophen amounts increase in the liver, the liver is often unable to easily metabolize higher dosages, and the creation of NAPQI in relation to the level of acetaminophen rises appreciably. Each individual has a different capcity for liver function, and liver function in each individual may vary considerably depending on liver stressors at any one point in time. The more drugs consumed, and the more alcohol, the more stress is placed on liver function. While alcohol is commonly known as a liver stressor, there are over 900 drugs implicated in potential liver injury, or hepatotoxicity. Concurrent use of pain medication with acetaminophen and alcohol is very common. FDA withdrawal of drugs from the market have occurred more frequently due to evidence of hepatotoxicity than perhaps any other cause. Drug induced liver injury is responsible for over 5 percent of all hospital admissions, yet this is rarely mentioned in health jounalism. A common test for liver malfunction is an enzyme assay, but a finding of liver enzymes (transanimases) that exceed a maximum normal is not a requirement of a diagnosis of liver damage, and is only one of a number of objective tests. It is well known that a number of serious liver diseases and dysfunctions may be diagnosed despite the findings of normal liver enzymes in the circulation. The body adapts in chronic diseases. This finding of high liver enzymes in circulation is more applicable to acute changes and onset of liver disease and toxicity. Many cases of acetaminophen overuse involve chronic hepatotoxicity, which may be hard to detect with standard medical tests.

Combining chronic use of pain medication with acetaminophen with prolonged use of other hepatotoxic pharmaceuticals, alcohol, or some recreational drugs, may be very problematic. For instance, salicylates, or aspirin, may cause acute liver damage if taken in doses of over 2 grams per day. Naproxen, while less damaging to the cardiovascular system than all other NSAIDS, is shown to potentially create acute dose-dependent liver damage, as are Carbamazepine and other anti-seizure medications used to also treat nerve pain, Ibuprofen and a number of medications used to treat high blood pressure, such as Dilitazem, Valproic acid, etc. Corticosteroid medications, now used in many medications to treat pain, asthma, skin disease, autoimmune disorders, etc. may cause fatty liver disease, along with immune suppressants such as methotrexate, prescribed for rheumatic diseases, and antithyroid medications. A large number of medications, especially antibiotics, may cause cholestatic disease of the liver, as well as oral contraceptives, tamoxifen, and anti-seizure medications prescribed for nerve pain. Chronic hepatitis may be caused by a number of drugs, not just viral diseases, and a number of commonly prescribed synthetic hormones may cause liver tumors and cancer, such as oral contraceptives, testosterone, and anabolic steroids. A list of such medications is available below in Additional Information, and patients taking such medications should be acutely aware of the increased risks associated with chronic pain medication use.

Liver damage, or hepatoxicity, may occur due to a number of mechanisms. Many chemicals, both drugs and environmental toxins, may damage mitochondria inside liver cells, decreasing cellular energy potential, and requiring an enormous increase in antioxidant and glutathione detoxifying capacity. Simple activation of some of the common pathways of breakdown of drugs, such as the P450 enzyme pathway, particularly the CYP2E1, have been shown to increase oxidative stress significantly, even under normal circumstances. With decreased cellular capacity and oxidative stress, accumulation of fats (e.g. lipoprotein cholesterol), which are broken down in the liver to create bile acids, occurs, and the term "fatty liver" is used to describe this condition, which is also highly associated with Metabolic Syndrome, or type 2 diabetes. Oxidative stress can also produce scarring, or sclerosis, of the liver channels, or hepatosclerosis. Both fatty liver and hepatosclerosis may lead to poor bile flow and excretion, and an accumulation of toxic bile acids in the liver. Bile acids are a family of acids, though, and some are created by other catabolic pathways. About a half of the cholesterol produced in the body (yes, almost all cholesterol is produced in the body, and not consumed in food) is used in bile acid synthesis. This is one reason why a finding of high cholesterol does not always mean simply that there is too much cholesterol leading to excess accumulation on the arteries. When hepatotoxicity occurs, backup of bile, accumulation of bile acids, ineffecient flow of bile (gallbladder sludge), gallstone formation, and other problems may occur. Drugs that block expression of cholesterol and lipoproteins may also have a negative effect on this toxic condition.

An array of common problems are associate with hepatoxicity, and potentially to the overuse of acetaminophen, NSAIDS, and steroids. These include hepatitis (liver inflammation), cholestasis (impaired bile flow), steatosis (fatty liver), granuloma (accumulation of immune cells that surround toxins and form spherical masses), vascular lesions (injury to blood vessels), and neoplasms (tumors and cancer). Diagnoses of these problems is problematic, and most cases are only diagnosed when serious or life-threatening signs and symptoms occur. This may only be the tip of the iceberg when considering the health problems associated with liver dysfunction, as the liver is the metabolic core of the human organism. The smart patient wants to avoid these problems, and when they are suspected, to treat or prevent them from getting worse. A wide variety of liver problems means that a wide variety of treatments may be applicable. A comprehensive array of treatments may be administered at once with standard TCM therapies that include acupuncture and herbal/nutrient medicine, combined with targeted dietary changes. There is no single herb or nutrient that will clear all of these problems. Searching for the magic pill or silver bullet is not an intelligent approach. Seeking knowledgeable treatment and advice from a professional is sensible.

A number of research studies have proven that an array of herbs and nutrient medicines do reduce acetaminophen toxicity. The most well known of these remedies include the shisandra berry extract (wu wei zi), milk thistle extract (Silybum marianum, especially standardized silymarin extracts), N-acetyl cysteine, and other products that boost glutathione metabolism (see a separate article on this website). Acute toxicity may be treated with digestive charcoal. Research for decades, though, especially in China, has revealed that a wide variety of Chinese herbs reduce hepatotoxicity, and are hepatoprotective. Formulas of herbs that achieve a variety of beneficial effects related to the problems described above are, of course, much more effective in achieving resolution of hepatoxicity than specific herbs. Dosage is also important, as well as quality of herbal medication. Utilizing top quality professional products may be all important. Relying on heavily advertised nonprofessional products is often a ticket for failure. Other formulas have been devised in Traditional Chinese Herbalism, or Chinese Herbal Medicine, that are gentler and hepatoprotective, rather than clearing of liver tissue and cellular pathology. Stronger formulas have been devised when dramatic signs of bile stasis, or sclerosis, are evident. If the liver toxicity has advanced to jaundice, meaning that the bile is backed up into the bloodstream, even stronger and more specific Chinese herbs and formulas will address this problem efficiently. A patient needs to consult a knowledgeable professional.

How to know whether you may have liver toxicity or damage from pain medications

When suspecting that you may have liver toxicity, liver damage, or liver dysfunction, the array of presentations, and the variety of the extent of problems, presents no single clear picture. Liver toxicity does not have a binary outcome, or a simple toxicity or not toxicity. Being aware of the nuances that may occur with liver toxicity, liver damage, and liver dysfunction helps you to objectively assess your situation and determine if you should go to an expert and start testing. If the presentation does not warrant testing, you might still receive some simple treatment to reverse dysfunction, clear toxins, and prevent more serious problems. Complementary Medicine offers a wide variety of solutions.

There are a number of signs and symptoms of acute liver toxicity, and not all of these are evident with every patient. When liver dysfunction is severe and acute, jaundice may occur. Jaundice is a yellowish staining of the whites of the eyes and skin due to bilirubin, a component of bile, overflowing or backing up into the circulating blood. Most often, severe jaundice is due to excessive destruction of red blood cells (usually in the spleen as a result of infection and inflammatory destruction), but when normal amounts of bilirubin go to the liver, and the liver cannot process them, a more gradual and milder form or jaundice may occur. This will usually only be noticed as a slight yellowish tint to the whites of the eyes. Other classic signs of acute liver toxicity include nausea, inexplicable vomiting, loss of appetite, fatique, abdominal pain (usually under the right ribcage), a feeling of abdominal swelling or tightness, itchy skin, darker urine, pale or greasy stool (inability to breakdown fats), dark stool (blood), and joint pain.

If acute liver toxicity is suspected, blood tests that reveal problems include, but should not be limited to, liver enzyme assays (ALT and AST are the most common tested). Necrosis (tissue death) of hepatocytes (liver cells) in toxic injury usually results in the leakage of enzymes into the circulation. In chronic liver diseases and toxicity, though, the rise in liver enzymes may not be dramatic, and may not exceed the normally accepted maximum levels related to disease. The change in liver enzymes is most important in these cases, yet this is rarely assessed. ALT (alanin aminotransferase) is associated not with miotchondrial destruction, but cytosolic, and serum level only correlated moderately with liver inflammation. AST (asparate aminotransferase) correlates more with toxic damage. If the toxicity creates less dramatic cell death, or apoptosis, it is presumed that the liver cells sythesize less AST and ALT as they die. Studies have shown that one third of patients with hepatitis C have persistently normal ALT levels, despite the presence of inflammation. Patients with cirrhosis also often have normal ALT and AST. If liver toxicity is suspected, more tests than just the liver enzymes need to be assessed.

Blood tests should assess albumin (the main blood protein made by the liver), ammonia (a measure of how the liver is breaking down proteins and dealing with the byproducts, or converting the ammonia from proteins broken down in the gastrointestinal tract by bacteria into urea), bilirubin (breakdown byproduct of bile metabolism), INR (a blood clotting test - the liver produces key clotting factors), and AFP (alpha-fetoprotein, a sign of potential liver cancer). Abnormalities should be assessed with nuance. If a serious problem is suspected, a liver biopsy will be ordered, but if the problem is not so serious, the medical doctor might tell you that all is well, no serious liver disease. This does not mean the a milder toxicity does not exist. Checking the levels yourself, and comparing to past tests, is a good idea, or bring the tests to a Complementary Medicine physician to assess for more nuanced changes that might indicate liver toxicity.

If more serious acute liver toxicity is apparent, ultrasound or MRI may be warranted to assess evidence of fatty liver or liver damage is areas of the liver. A CT is sometimes used, but the amount of harmful added radiation from these tests is a problem. Radioactive dye in liver scans also do not directly expose one to active radioactive substance, but the scan adds radiation, and the dye is somewhat toxic, which is a consideration for many.

A wide array of signs may accompany acute or chronic liver toxicity. The most common early subtle signs are general feelings of illness, flu-like symptoms and body aches. These are experienced in the abscence of an actual flu or cold. Lack of interest in food is a classic sign of liver dysfunction, as well as difficulty digesting fatty or greasy foods. Other signs include inexplicable widespread and espisodic itching, increased easy bruising and persistent bleeding, upper GI bleeding showing as darkened stool, dull mental functions (short term memory lapses, trouble concentrating) from accumulation of toxins in the brain, increased sensitivity to medications (drugs don't metabolize and clear as fast, with higher levels accumulating in the blood), and gallbladder discomfort (episodes of inexplicable nausea, fullness or tenderness under the rib cage, indigestion after eating), are all signs of chronic liver toxicity. Chronic liver cirrhosis may also cause immune dysfunction, intestinal infection, and lead to impotence, chronic kidney dysfunction, and osteoporosis (poor production of the hormone Vitamin D3 by the kidney regulating calcium in the body, or poor conversion of cholcalciferol prohormone to the prehormone calcidiol). Anemia may also be present. Since the liver is the most active detoxifier of the blood in the body, liver dysfunction may also cause increased systemic toxicity and accumulations of environmental toxins, such as heavy metals, as well as disseminated microbial infections, such as candida. Patients with chronic liver toxicity will be much more affected by alcohol, as the liver metabolism wants to process this carbohydrate acid quickly. This is the reason why some people will feel funny when drinking alcohol and consuming pain meds with a high dose of acetaminophen.

No matter what the degree of liver toxicity, a professional Complementary Medicine physician, such as a Licensed Acupuncturist and herbalist, if knowledgeable, can help resolve and restore. While it is true that liver dysfunction and toxicity may make it hard to break down even some herbal chemicals, this just shows that perhaps patients shouldn't self medicate with herbs in these situations. Monitoring and professional guidelines are very important, and are closely followed by a Licensed Acupuncturist, who receives a standard 4 year graduate medical school training, usually heavily tilted toward herbal medicine. Standard medicine, on the other hand, meaning medical doctors, have little or no training and education in herbal medicine. While medical doctors may be smart, one needs to be somewhat skeptical of their professional training, knowledge, and guidelines in this area.