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Posts Tagged ‘acetaminophen’

 

Acetaminophen: Is it Really Your Safest Option?

Friday, November 6th, 2015

By Tori Bumgardner, PharmD Student Cedarville University

Acetaminophen has long been a popular over-the-counter product used to treat pain and fever in both adults and children (1). It is recommended to women as the preferred pain medication while pregnant. The FDA has been approved for dosing in individuals of all ages, from infants to adults, who may be suffering from pain or fevers (2). While it is known that acetaminophen causes liver damage to people who take it at high doses for an extended period of time, recent studies have investigated the possibility that it can lead to dangerous levels of toxins in the body, potentially increasing the risk of attention deficit hyperactive disorder (ADHD) and even autism (3,4). The buildup occurs when one of the metabolites of acetaminophen, N-acetyl-p-benzoquinone imine (NAPQI), inhibits the detoxification of reactive oxygen species (ROS) in the body (5). When ROS builds up, inflammation can occur, giving it the potential to cause ADHD or autism. Additionally, a meta-analysis was conducted looking at the correlation between use of acetaminophen during pregnancy and occurrence of asthma in offspring (6). The study found that mothers who used acetaminophen while pregnant increased the risk of their child developing asthma. This blog post will review the recent evidence on the dangers associated with pre-natal exposure to acetaminophen.

Image courtesy of David Castillo Dominici at FreeDigitalPhotos.net

Image courtesy of David Castillo Dominici at FreeDigitalPhotos.net

A study from 2014 examined the relationship between mothers who took acetaminophen during pregnancy and the subsequent occurrence of ADHD in their children (4). In this study, 1714 European children were followed for 11 years and their mothers were surveyed when the children were newborn, 1, 3.5, 7, and 11 years old. For the newborn interview, information on the mothers’ pregnancy was collected. The other interviews were focused on the child, paying special attention to cognitive development, behavior, and physical activity. In the final interview, at age 11, the children also completed and interview that asked about topics like behavior, emotions, and self-esteem. The investigators examined the relationships between different drugs that were taken during pregnancy with the results of the strengths and difficulties questionnaire that were completed throughout the study. Interestingly, it was found that the group who used acetaminophen showed higher difficulties and lower social scores. The findings of this study indicate that acetaminophen use during pregnancy is correlated with higher rates of ADHD in children. Limitations to the study included a low follow-up rate, lack of generalization since the study was specific to European women and their children, and a possibility of selection bias if both parents were already predisposed to ADHD. Authors concede that additional research should be done to determine the actual risks associated with exposing children to acetaminophen at young ages. Other data found that children whose mothers used acetaminophen while pregnant had a higher incidence of behavior problems and hyperkinetic disorders (HKDs) like ADHD during a follow up when the children were seven years old (7). Due to the safety concern in allowing pregnant women to continue taking acetaminophen, since research seems to suggest its harm, the FDA has begun looking into the issue (8).

Though research is not yet conclusive, they encourage women to talk to their healthcare providers before taking anything.While it is always a good recommendation to talk to a doctor first, what does that leave women to use when they are in pain, but don’t have time to see or call the doctor, and are left with no options to provide relief? There are certainly alternatives available that don’t include drugs and can help relieve pain caused by headaches and aching in other parts of the body. Sometimes headaches are caused by stress and can be helped by practicing relaxation through deep-breathing, yoga, or any other technique that is convenient and will divert their mind off stress-inducing stimulation (9). A regular sleeping schedule is also important and exercise can help to relieve headaches, so taking a nap or a walk are both ways to relieve stress and pain without taking medication. Pain in other parts of the body may be troublesome, but a gentle massage or an external, topical pain relief product can be used to help establish comfort.

The data is still uncertain on the magnitude of risk with acetaminophen use in pregnant women, it is best to err on the side of caution and avoid use if possible. At the end of the day, the question that is left is one of risk versus benefit. Since nothing is conclusive about the danger that acetaminophen may have on babies, is it ultimately worth the risk to use it as a quick fix for a couple of hours free of pain?

 

References:

  1. Medline Plus: Trusted Health Information for You Web site. https://www.nlm.nih.gov/medlineplus/druginfo/meds/a681004.html. Published 08-15-2014. Updated 2014. Accessed October 16, 2015.
  2. DailyMed (package inserts). National Institutes of Health; National Library of Medicine.  http://dailymed.nlm.nih.gov/dailymed/ (accessed October 26, 2015).
  3. Jennifer Margulis PD. Could A common painkiller cause brain inflammation — and even autism — in children? http://reset.me/story/could-a-common-painkiller-cause-brain-inflammation-and-even-autism-in-children/. Published 09-08-2015. Updated 2015. Accessed 10-16-2015.
  4. Thompson JMD, Waldie KE, Wall CR, Murphy R, Mitchell EA, the ABC study group. Associations between Acetaminophen Use during Pregnancy and ADHD Symptoms Measured at Ages 7 and 11 Years. Hashimoto K, ed. PLoS ONE. 2014;9(9):e108210. doi:10.1371/journal.pone.0108210.
  5. Shaw W. Evidence that increased acetaminophen use in genetically vulnerable children appears to be a major cause of the epidemics of autism, attention deficit with hyperactivity, and asthma. Journal of Restorative Medicine. 2013;2:1. Accessed October 26, 2015. doi: 10.14200/jrm.2013.2.0101.
  6. Cheelo M, Lodge CJ, Dharmage SC, et al. Paracetamol exposure in pregnancy and early childhood and development of childhood asthma: A systematic review and meta-analysis. Arch Dis Child. 2015;100(1):81.
  7. Liew Z, Ritz B, Rebordosa C, Lee P,Olsen J. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatrics. 2014;168(4):313-320.
  8. FDA drug safety communication: FDA has reviewed possible risks of pain medicine use during pregnancy. U.S. Food and Drug Administration Web site. http://www.fda.gov/Drugs/DrugSafety/ucm429117.htm. Published 01-09-2015. Updated 2015. Accessed October 16, 2015.
  9. Krinsky D, Ferreri S, Hemstreet B, et al. Headache. In: Young L, ed. Handbook of nonprescription drugs: An interactive approach to self-care. 18th ed. Washington, DC: American Pharmacists Association; 2015:65-83-95. Accessed 10-16-2015.

Will treating a fever lead to wheezing?

Monday, November 24th, 2014

By Aric Carroll, PharmD Student

A young child is very susceptible to getting sick, and with that sickness often comes fever. How do most parents treat their child’s fever? The answer for the past few decades has been acetaminophen. In many countries around the world, the first line drug approved for treating fever in children is acetaminophen.1 It has been estimated from one study that up to 75% of all children in Western countries are at some time treated with fever reducing drugs such as acetaminophen.2,3 In the United States acetaminophen use without a physician visit is approved for children as young as 2 years old.4,5 In the past decade, a lot of research has looked at a connection between the rise of acetaminophen use and the rise of asthma in young children.6

A recent study from the Journal of Korean Medical Science (JKMS)9 investigated the relationship between acetaminophen use and asthma prevalence, but took it a step further to try to see why acetaminophen use could be associated with the condition of asthma. The study particularly looked at a specific gene for a receptor in the body called toll-like receptor 4 (TLR4). This is one of the first studies to focus on the combination of TLR4 modification and acetaminophen use and the risk of asthma associated with that combination. In past studies, modification of the gene for TLR4 has been associated with a higher prevalence rate of asthma.7 It has been suggested that modification at this particular gene affects how the TLR4 functions. Modifications may cause the body to work harder at dealing with fine particles that are inhaled leading to physical symptoms associated with asthma.8 The authors of the recent JKMS study acknowledge that TLR4 facilitates the symptoms of asthma by contributing to the release of reactive oxygen species, which are molecules that cause excess stress on the body. This excess stress can then lead to the release of cells that cause inflammation, cause the airways to be inflamed, and cause bronchial hyperresponsiveness (BHR) or tightening of the airways. The study suggests that modification of the TLR4 gene could cause the receptor to be more abundant and lead to greater asthma symptoms.9

The study examined 2, 428 children aged between 8 and 13. The parents of each child were asked to fill out a questionnaire, which included questions about whether the child had used acetaminophen, and whether the child had been diagnosed with asthma. Tests were run on each child to determine a forced expiratory volume after a methocholine challenge, which is an indicator of BHR. Methocholine causes constriction of the airways. BHR to methocholine was defined as a PC20 (the concentration of methocholine re-quired to provoke a 20% reduction in FEV1) ≤ 16 mg/mL. Genetic tests were run on each child to determine modification of the TLR4 gene. The results showed that the use of acetaminophen was associated with risk of BHR; however, it was not associated with actual asthma diagnosis. Modification of the TLR4 receptor was not associated with asthma diagnosis or risk of BHR. A combination of acetaminophen use and TLR4 modification was significantly associated with asthma diagnosis as well as risk for BHR. The study concluded TLR4 gene modification may increase the risk of asthma in children who have used acetaminophen.9

While the study had a very large sample size of children, it had limitations that could have affected the study’s results. The study only looked at acetaminophen use in the past 12 months, but did not take into account whether children had used acetaminophen in earlier years. Also, the study looked at patients with a recall of an actual diagnosis of asthma in the children instead of asking about certain symptoms of asthma such as shortness of breath during physical exercise, wheezing, or increased coughing. Many children may have had symptoms of asthma but had never been diagnosed by a physician. The study also did not in any way establish a relationship between dose or duration of acetaminophen use. Acetaminophen use was defined as if they took acetaminophen longer than 3 days in the last 12 months. This was also solely based on patient recall. These limitations are significant and reduced the generalizability of the study. This type of observational study cannot determine a causative relationship. Thus, this kind of research can only suggest potential risks associated with exposure.

While this study, along with others, have evidence to support a relationship between TLR4 modification and asthma, other similar studies have not found this relationship.10 The conflicting evidence on this specific mechanism makes it hard to conclude one way or another whether TLR4 modification is directly linked to asthma symptoms. Also, at this time there seems to be a lack of sufficient evidence to directly link acetaminophen use to asthma symptoms. More prospective research needs to be done looking at acetaminophen use and its relationship with asthma symptoms specifically in combination with TLR4 gene modification. It may be possible that acetaminophen has a greater adverse effect on children who have a TLR4 gene modification which would increase the risk of asthma specifically in those children. With what evidence is available at this time, it is difficult to say that treating a child with acetaminophen will cause them to develop asthma symptoms.

So, what are your thoughts? Even with this possibility of acetaminophen use in children leading to asthma symptoms, do you think it’s still reasonable for acetaminophen to be used to treat a child’s fever?

References

  1. Gonzalez-Barcala F, Pertega S, Silvarrey A, et al. Exposure to paracetamol and asthma symptoms. European Journal Of Public Health [serial online]. August 2013;23(4):706-710. Available from: Food Science Source, Ipswich, MA. Accessed October 15, 2014.
  2. Jensen J, Tønnesen L, Söderström M, Thorsen H, Siersma V. Paracetamol for feverish children: parental motives and experiences. Scandinavian Journal Of Primary Health Care [serial online]. June 2010;28(2):115-120. Available from: CINAHL Plus with Full Text, Ipswich, MA. Accessed October 16, 2014.
  3. Sullivan J, Farrar H. Fever and antipyretic use in children. Pediatrics [serial online]. March 2011;127(3):580-587. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed October 16, 2014.
  4. Reducing fever in children: safe use of acetaminophen. FDA Consumer Health Information. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm263989.htm. Published July 21, 2011. Updated June 6, 2014. Accessed October 15, 2014.
  5. Krinsky, D. L., Berardi, R. R., & Ferreri, S. P. (2011). Handbook of nonprescription drugs: An interactive approach to self-care (17th ed.). Washington, D.C: American Pharmacists Association.
  6. Farquhar H, Stewart A, Beasley R, et al. The role of paracetamol in the pathogenesis of asthma. Clinical & Experimental Allergy [serial online]. January 2010;40(1):32-41. Available from: Academic Search Complete, Ipswich, MA. Accessed October 15, 2014.
  7. Fagerås Böttcher M, Hmani-Aifa M, Vaarala O, et al. A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children. The Journal Of Allergy And Clinical Immunology. September 2004;114(3):561-567. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed October 16, 2014.
  8. Kerkhof M, Postma D, Koppelman G, et al. Toll-like receptor 2 and 4 genes influence susceptibility to adverse effects of traffic-related air pollution on childhood asthma. Thorax [serial online]. August 2010;65(8):690-697. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed October 18, 2014.
  9. Lee S, Kang M, Hong S, et al. Association between Recent Acetaminophen Use and Asthma: Modification by Polymorphism at TLR4. Journal Of Korean Medical Science. March 2014;29(5):662-668. Available from: Science Citation Index, Ipswich, MA. Accessed October 10, 2014.
  10. Hussein Y, Awad H, Shalaby S, Ali A, Alzahrani S. Toll-like receptor 2 and Toll-like receptor 4 polymorphisms and susceptibility to asthma and allergic rhinitis: A case-control analysis. Cellular Immunology [serial online]. 2012;274(1-2):34-38. Available from: Science Citation Index, Ipswich, MA. Accessed October 18, 2014.

Quality of Life Significantly Reduced In Acetaminophen-Induced Liver Failure

Monday, December 2nd, 2013

by Calvin Anderson, PharmD student

Acetaminophen, commonly known as Tylenol, is one of several analgesics available over-the-counter and is found to help alleviate symptoms such as headaches and fevers. Other available over-the-counter analgesics include ibuprofen, naproxen, and aspirin, which have different methods of action for treating pain. Acetaminophen is the most commonly used analgesic for pain relief in patients, and often people use it as needed without properly measuring how much they are taking; this can have severe consequences that people need to be aware of.1 Overdosing on acetaminophen can eventually lead to acute liver failure, which is a serious, potentially life-threatening condition that occurs when large parts of the liver become damaged beyond repair.2 According to a news article published in US news titled “Tylenol-Induced Liver Failure Presents Own Set of Problems: Study,” a recent study showed overdose survivors of acetaminophen-induced liver failure have considerably worse mental and physical health as compared to other patients suffering from liver failure induced by other causes. This article caught my attention because it directly correlated with self-care exclusion criteria regarding proper use of acetaminophen, which states that acetaminophen is potentially toxic to the liver in doses over 4 grams per day.3

The researchers who conducted this study found that patients who over-dosed on acetaminophen were reported to have more days of poor health and reduced physical activity due to pain, anxiety and depression experienced more so than other liver failure patients. They collected data from more than 280 patients diagnosed with liver failure between 1998 and 2010, and followed them for two years. The results were reported in Liver Transplantation, and were released this past July. According to the research, adult survivors of acute liver failure have reduced quality of life as compared to those of similar age and gender in the general population. An article called “Tylenol Safety: Is there Reason to Worry?”4 mentions that acetaminophen is the most commonly used medication for pain and fever in children, and there have been numerous reports of acute liver failure in children under eighteen years of age caused by ingesting too much acetaminophen. Prescribers and pharmacists alike must let their patients know about the risks of acetaminophen before allowing them to use it, especially for those patients already suffering from a liver condition, or those who chronically consume alcohol (more than 4 drinks per day.)3

It can be concluded from this study that there does exist an association between acetaminophen over-dose and quality of life among liver-failure patients. However, one thing I noticed about this article is that it failed to explain why the quality of life was worse in patients with acetaminophen-induced liver failure, as it did not establish a substantial cause-and-effect relationship. I would like to know why this is because the article did not address this issue. After properly ensuring that it is fine for the patient to take, I would still recommend acetaminophen as it is intended for the treatment of headaches, fevers, and pain. We as pharmacists must stress to our patients the potential risks of acetaminophen and be extra careful in our recommendations. One question I pose to my colleagues is: What are some effective ways we can bring to our patient’s attention the potential risks of Tylenol without scaring them?

 

Resources

1.) Johnson, Kimball. Liver Failure. Digestive Disorders Health Center http://www.webmd.com/digestive-disorders/digestive-diseases-liver-failure. Published July 11, 2012. Accessed November 5, 2013.

2.) Slack A, Wendon J. Acute liver failure. Clinical Medicine [serial online]. June 2011;11(3):254-258. Available from: Academic Search Complete, Ipswich, MA. Accessed November 29, 2013.

3.) Huckleberry Y, Rollins C. Analgesics. In: Krinsky D, ed. Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care. Washington DC: American Pharmacists Association; 67-72.

4.) Tylenol Safety: Is There Reason To Worry? Child Health Alert [serial online]. September 2006;24:1-2. Available from: Academic Search Complete, Ipswich, MA. Accessed November 5, 2013.