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Archive for the ‘Pain/Arthritis’ Category

 

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.

Tried everything for your headache?

Wednesday, November 5th, 2014

By Neal Fox, PharmD Student

One problem with treating headaches is that we don’t know exactly how they happen. Therefore, it is hard to know how to keep them from happening or even stop them once they start. When people have to deal with a headache on their own, they go to the pharmacy and buy something. They can take acetaminophen, ibuprofen, naproxen, or aspirin, which can potentially cause side effects if used too much. These drugs can also upset the stomach. For worse headaches prescription drugs are used, many of which have bad side effects and can be expensive. Melatonin can prevent and treat different types of headaches with few side effects and low cost.1,2 People who often get migraine headaches tend to not have enough melatonin inside of them.3 To fix this, melatonin can be taken as a pill.

A paper from India in September 2014, titled “Melatonin: functions and ligands”, detailed much about melatonin and all of the possible medical uses for it. Melatonin is created by the pineal gland, a part of the brain. Melatonin is related to sleep and it has been used to help people sleep better. There are many other things that melatonin can help with such as swelling, pain, and free radicals. This means that it could be involved in treating more diseases in the future.2 Right now, there is good evidence to support the use of melatonin for headaches. Using melatonin is very different from what Americas normally do. We use medications with unpleasant side effects that often work only in 50% of people who take them.4 Due to the research on melatonin being performed overseas, its benefits may not be well-known in America.

Around the world, scientists are looking at melatonin and headaches, and there are many studies supporting the use of melatonin in migraines as well.3 In a recent article from Turkey by researchers Karadas and Odabasi, 23 people were given 3 mg of melatonin before bed. This study found that, when taking melatonin, people had migraines less often. Plus, the migraines that they did have, hurt less. Because of this, the people taking melatonin needed to use other drugs less.5 Miano et al. found that melatonin 3 mg at bedtime was effective in reducing headache attacks in 22 children ages 6-16. However, 7 of the children reported no improvement.6 Melatonin has been used in other kinds of headaches, such as cluster headache. Cluster headache is a type of headache with really bad pain on one side of the head for a short time. This type also tends to mess up the body’s internal clock in different ways. Leone et al found that 10 mg of melatonin worked very well for half of people but another study by Pringsheim et al used only 2 mg and did not see any benefit.1,7 Finally, another type of headache called hemicrania continua (HC) is normally treated with a drug called Indomethacin, which has side effects including headache. HC is a type of headache that lasts for a long time and is usually on one-side of the head but not very bad. However, at times this headache can become much worse and the severe pain can last for hours or days.  Melatonin has been used to help people with HC and has been very successful.8,9 Finally, a Dutch group treating sleep patients found that 78.6% of them had a decrease in headaches with melatonin. However, 13.8% of patients who didn’t have headaches before, got them while on melatonin.10

We don’t know exactly how melatonin works for headache. A possibility suggested by some experts is all about the internal sleep clock that we have and melatonin’s effect on that. The research that has been done so far shows good things about melatonin. We know that it is highly safe and inexpensive. The only reported side effects of melatonin are that it can make people really sleepy and might cause headaches in some people with sleep disorders.10 If you think melatonin may be beneficial to you, talk with your doctor and make an informed decision together. Melatonin may not work for everyone, because of the complexity of headaches and the different kinds. But if it could work, is it worth it to try?

Kaitie’s Story

Since I was thirteen, I used to get terrible headaches 3-5 times a week. I started taking melatonin (3 mg before bed) in April of 2013 and have only had about 10 major headaches since then (currently October 2014). The main issue I have had with taking melatonin regularly is that it can be more difficult to get out of bed due to drowsiness; but this usually subsides within 30 minutes of actually getting up. I would definitely recommend trying melatonin for prevention of frequent headaches.

Have you tried everything for your headache? Are you willing to try melatonin?

 

References:

  1. Pringsheim T, Magnoux E, Dobson CF, Hamel E, Aubé M. Melatonin as adjunctive therapy in the prophylaxis of cluster headache: A pilot study. Headache. 2002;42(8):787-792.
  2. Singh M, Jadhav HR. Melatonin: Functions and ligands. Drug Discov Today. 2014;19(9):1410-1418.
  3. Vogler B, Rapoport AM, Tepper SJ, Sheftell F, Bigal ME. Role of melatonin in the pathophysiology of migraine: Implications for treatment. CNS Drugs. 2006;20(5):343.
  4. Peres M, Masruha M, Rapoport A. Melatonin therapy for headache disorders. Drug Development Research (USA). 2007;68:329-334.
  5. KARADAS Ö, ODABASI Z. Migrende melatonin proflaksisinin etkinligine yönelik açik uçlu klinik çalisma: Ön rapor. Archives of Neuropsychiatry / Noropsikiatri Arsivi. 2012;49(1):44-47.
  6. Miano S, Parisi P, Pelliccia A, Luchetti A, Paolino MC, Villa MP. Melatonin to prevent migraine or tension-type headache in children. Neurol Sci. 2008;29(4):285-287.
  7. Leone M, D’Amico D, Moschiano F, Fraschini F, Bussone G. Melatonin versus placebo in the prophylaxis of cluster headache: A double-blind pilot study with parallel groups. Cephalalgia. 1996;16(7):494-496.
  8. Hollingworth M, Young T, M. Melatonin responsive hemicrania continua in which indomethacin was associated with contralateral headache. Headache. 2014;54(5):916-919.
  9. Rozen TD. Melatonin responsive hemicrania continua. Headache. 2006;46(7):1203-1204.
  10. Rovers J, Smits M, Duffy JF. Headache and sleep: Also assess circadian rhythm sleep disorders. Headache. 2014;54(1):175-177.

New research finds acetaminophen use during pregnancy is associated with ADHD in offspring

Tuesday, November 4th, 2014

By: Jeremy Flikkema Cedarville University PharmD Student

Acetaminophen is a commonly recommended over the counter medication given to pregnant women for treating mild pain. Recently however, the safety of this medication was put under investigation after JAMA Pediatrics published a study that found links between acetaminophen use and attention deficit/hyperactivity disorder (ADHD).1 This is alarming because acetaminophen is preferred over other pain killers. Non-steroidal inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, and aspirin are not recommended during pregnancy due to potential birth defects in the offspring.2

ADHD is characterized as a behavioral disorder affecting 5-10% of the school age population.1 Symptoms include inability to concentrate, impulsivity, and/or hyperactivity all of which can impact performance at work and school. Acetaminophen use during pregnancy led to an increase probability of their offspring taking ADHD medications and developing a hyperkinetic disorder.3 To clarify, hyperkinetic disorders are a more severe form of ADHD.

The recently published Danish prospective cohort interviewed 64,322 live-born children and mothers from 1996-2002.1 They did three telephone interviews during pregnancy followed by a fourth interview six months after giving birth. In this study, over half of the women had admitted to taking acetaminophen at some point during pregnancy. The characteristics of interest were hyperkinetic disorders, use of ADHD medications, and/or having ADHD-like behaviors at age 7. All three of these variables were found to be significantly increased due to acetaminophen use. Increased frequency of use and long duration (more than 1 trimester) both increase the associations that were observed. This study’s strength was the large sample size, prospective study design that eliminated recall bias by the mothers, and because it measured more than one variable. However, the limitation of this study was the design type.3 Cohort studies only infer association not causation. Therefore, results must be interpreted cautiously until further research is done.

Additional research has been done regarding this topic. A Norwegian prospective cohort found that acetaminophen use for more than 28 days or more correlated with reduced gross motor skills, delay in walking, increased activity, reduced communication skills, and attention-seeking behavior.4 This study supports the association between acetaminophen use and ADHD. Another study tested the effect of other drugs (aspirin, antacids, and antibiotics) and found no correlation in regards to behavioral difficulties at age 7.3 These strengthen the evidence that acetaminophen use increases the risk of ADHD.

Before this research, acetaminophen was considered safe to use throughout all trimesters of pregnancy for pain, fever, and colds and was used by 55 to 65% of pregnant women.5 These new research findings suggest potential changes to the standard of care, further prospective research is required to determine if acetaminophen is the true cause. Until then acetaminophen during pregnancy should be used with caution and only when necessary. There are many different ways to relieve pain in a non-pharmacological manner such as; sleeping with lots of pillows for support, drinking lots of water, gentle exercise, massages, and taking warm baths, music, and yoga can increase the health of your baby.6 There are many harmful effects that medications can have on our bodies that may still be unknown. If however, the medication is used, it is of uttermost importance to limit the duration and frequency.

Knowing the potential risk with Acetaminophen use and ADHD, do you think the risk outweighs the benefit?

 

Bibliography:

  1. Liew Z, Ritz B, Rebordosa C, Lee PC, Olsen J. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatr. 2014;168(4):313-320.
  2. CAZACU I, FARCAŞ A, MOGOŞAN C, BOJIŢĂ M. Safety of over-the-counter medication in pregnancy. sometimes a dilemma. Clujul Medical. 2011;84(3):348-354.
  3. Thompson JMD, Waldie KE, Wall CR, Murphy R, Mitchell EA. Associations between acetaminophen use during pregnancy and ADHD symptoms measured at ages 7 and 11 years. PLoS ONE. 2014;9(9):1-6.
  4. Brandlistuen RE, Ystrom E, Nulman I, Koren G, Nordeng H. Prenatal paracetamol exposure and child neurodevelopment: A sibling-controlled cohort study. Int J Epidemiol. 2013;42(6):1702-1713.
  5. Blaser JA, Allan GM. Acetaminophen in pregnancy and future risk of ADHD in offspring. Can Fam Physician. 2014;60(7):642-642.
  6. Pritham U, McKay L. Safe Management of Chronic Pain in Pregnancy in an Era of Opioid Misuse and Abuse. JOGNN: Journal Of Obstetric, Gynecologic & Neonatal Nursing [serial online]. September 2014;43(5):554-567. Available from: CINAHL Plus with Full Text, Ipswich, MA. Accessed November 3, 2014.

 

 

Can Ginger Cure Rheumatoid Arthritis?

Tuesday, November 4th, 2014

by R. Brandon Kime, PharmD Candidate

Rheumatoid arthritis is a disease that causes the breakdown of joints throughout the body due to the body’s immune system attacking these tissues. As the joints degrade, they become less able to support and lubricate the bones that they attach. Eventually, the bones can rub together, causing erosion of the bone and possibly deformity of the joint. This entire process results in a considerable amount pain for those affected, as well as difficulties in day-to-day functioning. Unlike other types of arthritis, rheumatoid arthritis can occur in people of all ages. Rheumatoid arthritis is usually treated by prescription drugs that decrease inflammation or decrease immune system activity. Some of these drugs may have significant side effects, including increased chance for infection for those that suppress the immune system, or increased chance for ulcers and bleeding for anti-inflammatory drugs. Physical therapy may also be used to increase joint flexibility and decrease stress and degradation of the joints. One European study estimated the total cost of rheumatoid arthritis in the US as 42 billion euros,1 or over 53 billion dollars.

Plants have been used since ancient times for medicinal purposes,2 and traditional medicine is growing acceptance in developed countries.3  An article written by Al-Nahain and colleagues evaluated the potential of the ginger plant (Zingiber officinale) in treating rheumatoid arthritis.4 The root of the ginger plant is most often used in food because of its unique taste, but it also has several medicinal properties that have been observed. Ginger has been well-studied for its anti-inflammatory effects (it is similar in action to aspirin or ibuprofen).5,6 The plant contains many drug-like compounds that may be useful in either treating rheumatoid arthritis outright or developing new anti-inflammatory drugs.2 One study tested both ginger extract as well as several chemicals isolated from ginger in an animal model of rheumatoid arthritis and found ginger to have “profound antiarthritic efficacy.”7 This means that ginger is capable of treating arthritis on multiple levels. While ginger may have potential in treating arthritis, it would not be without disadvantages. There is a lack of precise dosing information for this application of ginger. Furthermore, since it is considered a dietary supplement insurance companies would be unlikely to cover it.

While “cure” is far too strong of a word at this time, what does all this mean for those struggling with rheumatoid arthritis? First, it gives them a potential option when standard therapies do not work well enough to treat their symptoms. Individuals suffering from the disease can talk to their doctors and discuss whether using or adding a ginger supplement to their regimen could be beneficial in treating their symptoms. Second, it gives them hope for future research to find more effective treatments for rheumatoid arthritis. The Al-Nahain article is optimistic that further research into the chemical functions of ginger components, “may make it possible to stop further progress or even reverse the damage caused by [rheumatoid arthritis].”2 Finally, if new research into ginger prompts further research into the benefits of other substances marketed as dietary supplements, I think that is good for the world of healthcare as a whole. Selecting healthcare products should be based on evidence rather than advertising. I would recommend that consumers become proactive in discovering the benefits of both mainstream and alternative treatments. In this way, consumers can make more informed decisions and progress can be made in treating various diseases.

Has anyone you have known taken a ginger supplement for their rheumatoid arthritis? How well did his or her treatment work?

References

  1. Lundkvist J, Kastäng F, Kobelt G. The burden of rheumatoid arthritis and access to treatment: Health burden and costs. The European Journal of Health Economics. 2008;8(, Supplement 2: The Burden of Rheumatoid Arthritis and Patient Access to Treatment):S49-S60.
  2. Phillipson JD. Phytochemistry and medicinal plants. Phytochemistry. 2001;56(3):237-243.
  3. World Health Organization. WHO traditional medicine strategy 2002-2005. 2002.
  4. Al-Nahain A, Jahan R, Rahmatullah M. Zingiber officinale: A potential plant against rheumatoid arthritis. Arthritis. 2014;2014:8.
  5. Grzanna R, Lindmark L, Frondoza CG. Ginger-an herbal medicinal product with broad anti-inflammatory actions. Journal of medicinal food. 2005;8(2):125-132.
  6. Mascolo N, Jain R, Jain SC, Capasso F. Ethnopharmacologic investigation of ginger (zingiber officinale). J Ethnopharmacol. 1989;27(1–2):129-140.
  7. Funk JL, Frye JB, Oyarzo JN, Timmermann BN. Comparative effects of two gingerol-containing zingiber officinale extracts on experimental rheumatoid arthritis⊥. J Nat Prod. 2009;72(3):403-407.

Exercise to Save Your Knees

Monday, December 2nd, 2013

by Jeniffer George, PharmD student

An estimated 27 million adults in the United States suffer from osteoarthritis of the knee or hip which is commonly seen in patients 65 and older.1 Osteoarthritis is the breakdown in cartilage that covers the ends of the bone to where they meet and form a joint to allow movement.1 As of today, researchers have not found a set cure for arthritis, however, mild pain relief can be found from the use of NSAIDS, acetaminophen and combination products such as glucosamine and chondroitin. In addition, with the increase in obesity in the United States, exercise can relieve stress that is placed on the knees for patients with osteoarthritis. A survey conducted by the Centers for Disease Control and Prevention showed 53% of patients with arthritis didn’t walk at all for exercise, and 23% meet the current recommendation for activity—walking for at least 150 minutes a week.2 So the question I pose is: as future pharmacists, should we recommend glucosamine and chondroitin or exercise to patients with osteoarthritis?

For almost 20 years, the nutritional supplement glucosamine and chondroitin has been marketed to the public for joint health. Glucosamine is an amino sugar that can help renew cartilage while chondroitin is thought to be a complex carbohydrate that helps cartilage retain water.3 Glucosamine and chondroitin are found as natural substances in and around the cells of cartilage.3

NPR recently released an article that presented a study published by the New England Journal of Medicine (NEJM) and another study by the Journal of American Medical Association (JAMA). The study found in NEJM, involved 1,583 randomly selected patients receiving glucosamine and chondroitin with placebo.4 They found that glucosamine/chondroitin, in comparison with placebo seemed to show no effect on patients with osteoarthritis, however, a smaller subgroup characterized with moderate to severe pain showed a significant reduction of knee pain after the use of glucosamine. The study was conducted well, however, patients measured at baseline reported having mild knee pain, as compared with that in classic studies of osteoarthritis, in which a criterion for entry was a disease flare after the discontinuation of NSAIDs.4 In general, the evidence on glucosamine/chondroitin is varied, leaving it difficult to answer if the use of supplements are proven to be effective.

The second study presented in JAMA, included 399 participants that are overweight and presented with knee osteoarthritis. Participants in the study endured 18 months of combined intense diet and exercise modifications to see if there would be an increase in knee function and reduction in pain. Participants in the diet and exercise and diet groups had greater reductions in Interleukin 6 (used to measure inflammation) levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group.5 The article does a great job on emphasizing the importance of exercise, however, patients with moderate to severe osteoarthritis, who may have difficulty exercising were excluded from the study.

I agree with most of the content in the article and seem to agree with the studies associated with the material. As a future pharmacist, I would recommend using glucosamine and chondroitin in conjunction with exercise while living a healthy dietary lifestyle to help patients with osteoarthritis. It is human nature to avoid doing things when you are in pain. Patients with osteoarthritis may avoid exercise when a hip, knee, or other joints hurt. As shown in the NEJM study, patients with moderate-to-severe pain saw a reduction in pain after using glucosamine and chondroitin. Recommending glucosamine and chondroitin can help patients have temporary relief in pain, which can enable them to engage in low impact activities, get the heart rate up and burn calories. If exercise is not an option for the patient, guiding the patient in dietary modifications can help in weight reduction. Other treatment options include: rest which helps reduce stress and tension that is put on the knees, hot and cold therapy to help increase blood flow and reduce inflammation near the joint area, and to avoid standing in one position for an extended time.

With studies like these, would you suggest glucosamine and chondroitin as a form of therapy? How can you advise a patient that is adamant on not losing weight due to the pain they are experiencing?

 

References

 

  1. National Center for Complementary and Alternative Medicine. http://nccam.nih.gov/research/results/gait/qa.htm. Published May 2002. Updated October 2008. Accessed November 1, 2013.
  2. Skerrett PJ. Exercise is good, not bad, for arthritis. Harvard Health Publication Web site. http://www.health.harvard.edu/blog/exercise-is-good-not-bad-for-arthritis-201305086202. Published May 8,2013. Accessed November 21, 2013.
  3. Patti Neighmond. National Public Radio. National Public Radio Website. http://www.npr.org/blogs/health/2013/10/14/231451187/exercise-may-help-knees-more-than-glucosamine-and-chondroitin?utm_content=socialflow&utm_campaign=nprfacebook&utm_source=npr&utm_medium=facebook. Published October 14, 2013. Accessed November 1, 2013
  4. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis. N Engl J Med. 2006;354(8):795-808.
  5. Messier SP, Mihalko SL, Legault C, et al. Effects of Intensive Diet and Exercise on Knee Joint Loads, Inflammation, and Clinical Outcomes Among Overweight and Obese Adults With Knee Osteoarthritis: The IDEA Randomized Clinical Trial. JAMA. 2013;310(12):1263-1273. doi:10.1001/jama.2013.277669.Accessed November 1, 2013.

 

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.

Exercise to Improve Back Pain

Tuesday, November 26th, 2013

By Gina Mattes, PharmD Student Cedarville University

Today almost 80% of  Americans have back pain, but often the treatments used are ineffective and costly. 1 However, there is another way that people can relieve back pain that is relatively cheap or free and you can do it right at home! Exercise is being proven to be more beneficial for your heart, but it’s also better for pain.1 In an article posted in The New York Times a study was cited that showed even going for a walk every day can help reduce back pain.1 This conclusion was made because there was no statistical difference between the exercise group and the walking group with significant improvement in walking distance from the beginning to the end in both groups.2 The six minute walk test was the main outcome for the study.  Both groups participated in a six-week program that was twice a week. Both groups started with 20 minutes during each session and increased by 5 minutes every week. The walking group spent time on a treadmill starting at a low intensity, increasing intensity, then had a cool down with low intensity at each session. The exercise group focused on active movement and strengthening exercises, beginning with a five minute warm up, low loaded exercise increasing the number of exercise repetitions over the course of the 6 weeks, and a five minute cool-down.2

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Another way to reduce chronic pain The New York Times article proposes is doing yoga. One study showed that yoga for short-term effectiveness helped tremendously, but only moderate outcomes for long-term effectiveness.3 The reason exercise has been helping rather than hurting is because you are strengthening the muscles in your back and abdomen, in doing this you are able to regain function of your back without pain because of the endurance your body has built up.2 In the study presented by the Clinical Journal of Pain Cramer and colleagues looked at 10 randomized clinical studies that collectively had 967 chronic back pain patients that showed strong evidence for short term relief and moderate evidence for long-term relief.3 There is no simple solution or usually a reason for back pain to be occurring, but even if there is no reason for the pain people don’t have to be in pain instead they can go for a walk and build up those muscles. I agree with this article. It’s easier and way cheaper to go outside and walk around the block a few times, going to the gym, or looking up youtube yoga videos to do some yoga and help yourself than taking medications that probably won’t help in the long run.

Studies have show that the standard of care for lower back pain such as steroid shots, has often  been ineffective for chronic pain. 3, 4 Additional evidence shows that people doing yoga to relieve chronic back pain is much more helpful.1,2,3  In a study done by Saper he came up with a 12 week hatha yoga program.5 The study included a 12 week yoga program with each session lasting about 75 minutes, led by a 2 year yoga expert.5 The program was broken up into four, three week segments with each week containing a different theme.5 The participants were strongly encouraged to practice yoga for 30 minutes each day, the participants were given all material needed to practice at home.5 Improvement was evaluated by questionnaires that participants filled out at 6 and 12 weeks of intervention.5 At the end the study showed that participants’ pain decreased resulting in the decrease of using pain medications and muscle relaxants.5 However, the study did have a high number of drop out rates and a low number of follow up at 26 weeks.5 Even with the issues of the study it still shows a significant difference in people who did a yoga program versus the people who did not.5

The increase in studies that exercise in some form helps chronic pain patients long-term are overwhelming. Even a short day trip in a study done in Japan where people went to an amusement park for the day had pain relief, but the relief quickly faded after that day.2,3 This study included several age groups and measured back pain at different times (10 minutes, 1 hour,and 3 hours after arriving), but had a low number of participants in the study making it more questionable.3 In light of this new evidence I would highly recommend to my patients to try and build those lower back and abdomen muscles by going for a walk or maybe even looking up a few easy exercises online instead of jumping to steroid shots. In the end walking around the block would likely be more beneficial to health holistically than medication therapy.

So which would you rather have, going for a walk every day or sitting in the doctor’s office waiting for a shot that may not have long term effectiveness?

References:

1. Reynolds, G. Alternatives for back pain relief. The New York Times. July 18, 2013:MM18. October 21, 2013 http://well.blogs.nytimes.com/2013/07/18/looking-for-alternatives-for-back-pain-relief/?_r=0

2.   Shnayderman I, Katz-Leurer M. An aerobic walking programme versus muscle strengthening programme for chronic low back pain: a randomized controlled trial. Clinical Rehabilitation [serial online]. March 2013;27(3):207-214.

3.   Centre for Reviews and D. A systematic review and meta‐analysis of yoga for low back pain (Provisional abstract). Clinical Journal Of Pain [serial online]. 2013;:450-460.

4.   Staal J, Nelemans P, de Bie R. Spinal injection therapy for low back pain. JAMA: The Journal Of The American Medical Association [serial online]. June 19, 2013;309(23):2439-2440.

5.   Saper R. Yoga for Chronic Low Back Pain in a Predominantly Minority Population: A Pilot Randomized Controlled Trial. Alternative Therapies In Health & Medicine [serial online]. November 2009;15(6):18-27.

6.   Sakakibara T, Wang Z, Kasai Y. Does going to an amusement park alleviate low back pain? A preliminary study. Journal Of Pain Research [serial online]. January 1, 2012;5:409-413.

The Impact of NSAIDs on Depression in Osteoarthritis Patients

Wednesday, November 6th, 2013

By Anna Smith, Cedarville University PharmD Student

Imagine waking up every morning for the rest of your life with stiff, aching joints. This is what people with osteoarthritis have to go through.  Osteoarthritis is the result of cartilage breakdown in the joints and can result in pain, swelling, and reduced joint motion.1  It is estimated that 27 million Americans suffer from osteoarthritis, which is a chronic condition.  Although there is no cure, medications have helped to relieve pain.2  On top of the daily pain endured, osteoarthritis patients are twice as likely to struggle with depression.3

Fox News recently released an article about a study published by The American Journal of Medicine.  The study found non-steroidal anti-inflammatory drugs (NSAIDs) used to relieve pain from osteoarthritis, such as ibuprofen and naproxen, may also play a role in reducing depression related to osteoarthritis.  The study used approximately 1500 osteoarthritis patients not taking antidepressants.  Patients were either given over-the-counter (OTC) NSAIDs, Celebrex, or a placebo to observe the impact on depression.3  Depression was measured using the Patient Health Questionnaire (PHQ-9) constructed by Pfizer, using a scale of 0-27.  The total points scored in the questionnaire represent different categories of depression, 1-4 being minimal depression, 5-9 as mild depression, 10-14 as moderate depression, 15-19 as moderately severe depression, and 20-27 being severe depression.4  The median score for the patients before treatment was 3, showing scores were low and around the minimal depression range.  Results showed combined data of OTC NSAIDs and Celebrex lowered depression scores significantly more than the placebo (p<0.039).  However, OTC NSAIDs alone did not have a significant impact compared to the placebo in lowering depression symptoms (p=0.087).  With these results, researchers are suggesting NSAIDs may help reduce depression symptoms in osteoarthritis patients.5

Research on the relationship between NSAIDs and depression is lacking.  The only outside source supporting the use of NSAIDs for depression dealt with interferon-induced (IFN-induced) depression.  This article stated interferon-alpha (used for treatment in some chronic diseases and viral illnesses) can cause depression as a side effect.  NSAIDs are known to treat many IFN-induced side effects. The article suggests NSAIDs could play a role in reducing IFN-induced depression.6  Although NSAIDs could possibly reduce this type of depression, they have been found to interact negatively with antidepressants.  A study showed that NSAIDs were linked to increased depression in patients using selective serotonin reuptake inhibitors to treat depression.7  This suggests simultaneous use of NSAIDs and antidepressants may reduce effectiveness of depression treatment.

By looking through outside sources, it is clear the study on NSAIDs easing depression is limited.  First, there is not enough outside literature and research to support NSAIDs playing a role in depression.  Also, the results could have been due to pain relief.  Rather than having a direct method of action in reducing depression, the treatment could have relieved pain and put patients in a better mood.  The study also stated OTC NSAIDs, Celebrex, and placebo all reduced depression scores.  Since patients taking the placebo were also less depressed, this could mean outside factors altered their mood.  Furthermore, the median score of depression on the PHQ-9 scale before treatment was a 3.  With a score of 3, patients are thought to only have minimal depression, which is the lowest depression category on the scale.4  Without having higher scores, I feel that the data does not accurately represent patients who are truly depressed.

Taking the study and outside research into consideration, I would still recommend using NSAIDs for relieving osteoarthritis pain.  These medications can still be effective in the relief of pain.  However, I would not recommend NSAIDs for treating depression since there is currently no evidence that NSAIDs work to treat depression alone.  Since NSAIDs have been shown to interfere with antidepressant treatment, I would also advise caution when recommending NSAIDs to patients taking antidepressants.

I do not agree with the study that NSAIDs play a role in easing depression of arthritis patients.  There are too many limiting factors to the study and not enough supporting evidence.  There was no significant difference observed between OTC NSAIDs and the placebo on lowering depression symptoms.  Also, the participants did not have high depression scores to start out with.  Additional resources do not support a mechanism for NSAIDs lessening depression.

There does not appear to be a significant amount of research on NSAIDs and depression.  The study mentioned by Fox News may lead to new research studies dealing with NSAIDs and depression, which may clarify a direct or indirect correlation.  The link between pain and depression is complex, and depression may only be lessened by NSAIDs due to their influence on pain.  Until further research is conducted, we must ask – do NSAIDs truly play a significant role in reducing depression?

 

 

References

  1. U.S. National Library of Medicine. Osteoarthritis. MedlinePlus. http://www.nlm.nih.gov/medlineplus/osteoarthritis.html. Updated September 27, 2013.  Accessed October 27, 2013.
  2. Arthritis Foundation. Osteoarthritis. Arthritis Foundation. http://www.arthritis.org/conditions-treatments/disease-center/osteoarthritis/. Accessed October 27, 2013.
  3. Ibuprofen may ease arthritis patients’ depression. Fox News http://www.foxnews.com/health/2013/09/26/ibuprofen-may-ease-arthritis-patients-depression/. Published September 26, 2013. Accessed October 27, 2013.
  4. Pfizer Inc.  Patient Health Questionnaire (PHQ-9).  SAMHSA-HRSA Center for Integrated Health Solutions.  http://www.integration.samhsa.gov/images/res/PHQ%20-%20Questions.pdf.  Accessed November 1, 2013.
  5. Iyengar, RL, Gandhi S, Aneja A, Thorpe K, Razzouk L, Greenberg J, Mosovich S, Farkouh M. NSAIDs Are Associated with Lower Depression Scores in Patients with Osteoarthritis. The American Journal of Medicine. 2013;126(11):1017.e11-1017.e18.http://www.sciencedirect.com/science/article/pii/S0002934313003586. Accessed November 1, 2013.
  6. Asnis GM, De la Garza II R, Kohn SR, Reinus JF, Henderson M, Shah J. IFN-induced depression: a role for NSAIDs. Psychopharmacol Bull. 2003;37(3):29-50.  http://www.ncbi.nlm.nih.gov/pubmed/14608239. Accessed October 27, 2013.
  7. Gallagher PJ, Castro V, Fava M, Weilburg JB, Murphy SN, Gainer VS, Churchill SE, Kohane IS, Iosifescu DV, Smoller JW, Perlis RH. Antidepressant Response in Patients with Major Depression Exposed to NSAIDs: A Pharmacovigilance Study. Am J Psychiatry.  2012;169(10):1065-1072. doi:10.1176/appi.ajp.2012.11091325.

 

The Importance of Acetaminophen Overdose Education

Friday, November 1st, 2013

by Rachel Kunze

Acetaminophen, also known as Tylenol, is a popular analgesic that can be bought over the counter. Like many drugs, acetaminophen has serious health consequences if the maximum dose is exceeded.1 Tens of thousands people each year end up in the hospital due to acetaminophen overdose and 150 of these cases are fatal due to acute liver failure.2 Factors that increase the risk for liver toxicity include long term alcohol use and use of drugs that are broken down by the cytochrome P450 2E1 enzyme system, including acetaminophen.3 A recent article entitled Tylenol’s Risks Not Fully Understood, Poll Shows explored the public’s knowledge on this drug. Shockingly, fifty-one percent of people surveyed were not aware of any warnings with acetaminophen usage. Forty-nine percent incorrectly said that an acetaminophen overdose would cause heart palpitations. Thirty-five percent of those surveyed believed it was safe to take two products containing acetaminophen simultaneously.1 In response to these polling results, the FDA has launched a safety campaign known as The FDA’s Safe Use Initiative in order to raise awareness of acetaminophen’s risk factors.1 This campaign includes a webpage, pamphlets, and a YouTube channel on the risks associated with acetaminophen. Tylenol manufacturers have also taken steps to raise awareness by making posters for doctors’ offices and making a YouTube channel of their own.1 This article only used polls to measure patient awareness, so threats to validity were possible. The article did not explain factors that may have led to a certain survey response, such as a career in health care.

I was surprised to learn that a large percentage of the public was unaware of the safety concerns with acetaminophen. I agree with the article that steps need to be taken to improve patient education on this issue. Despite the safety concerns, this would not change my self-care recommendations. I still see acetaminophen as an effective analgesic, but would take the time to warn my patients about the health risks. One study determined that out of 662 cases of acute liver failure in a hospital, 42 percent of them had to do with misuse of Tylenol.2 I believe that many hospital visits could be avoided if patients were more aware of the safety concerns with Tylenol products. While it may be true that the FDA campaign may reduce the number of hospital visits, I believe that even more should be done. The FDA’s creation of a YouTube channel, for example, will only help if a patient happens to find it on the internet. What about those who do not own a computer? A patient should not have to go out of their way to be educated on a medication, even if it can be bought over the counter.  I believe something should be done in pharmacies to more directly educated patients. Pharmacists should take a direct role in educating patients in person. Flyers that warn about overdoses should be put up next to the acetaminophen products in pharmacies.  This way, a pharmacist can warn the patient on the maximum dosage and what can happen if there is an overdose of the drug. It would not take up too much of a pharmacist’s time and can be a very effective way to educate the public. This is just one possible solution to the issue. Based on the statistics this article gave, are the safety concerns severe enough to take more initiative? If so, should Tylenol maybe become a behind the counter drug so the pharmacy can further monitor its usage? How else can we reduce the number of acetaminophen overdoses?

 

References

[1] Miller TC,  Gerth J. Tylenol’s Risks Not Fully Understood, Poll Shows. ProPublica: Journal in the Public Interest. 2013. Available at: http://www.propublica.org/article/tylenols-risks-not-fully-understood-poll-shows. Accessed October 7, 2013.

[2] Larson A. M., Polson  J., Fontana  R. J., Davern T. J. et. al. Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective study. Hepatology [serial online]. 2013;42(6): 1364-1372. Available at: http://onlinelibrary.wiley.com/doi/10.1002/hep.20948/full. Accessed October 11, 2013.

[3] Kozer E, Koren G. Management of Paracetamol Overdose: Current Controversies. Drug Safety [serial online]. January 1, 2001;24(7):503-512. Available from: E-Journals, Ipswich, MA. Accessed October 20, 2013.

Should OTC Painkillers Used After Tonsillectomy Instead of Standard of Care?

Thursday, October 24th, 2013

By Megan McNicol, Cedarville University PharmD Student

 

In the United States, a tonsillectomy is the second most common outpatient surgery for children younger than 15.  Each year, an estimated 662,000 American children have a tonsillectomy.1   This procedure is performed when there are recurrent episodes of tonsillitis or bacterial infections causing tonsillitis that are not improving with the use of antibiotics.  As a result, a procedure is often performed to remove the tonsils.2  While the surgery is usually successful, pain is a common side effect following a tonsillectomy and can lead to dehydration, difficulty swallowing and weight loss.  For this reason, some sort of pain reliever is necessary to manage the symptoms. 1

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The article, “After tonsillectomy, over-the-counter painkillers suffice” published by US News and Health discussed how researchers performed a study examining 25 children and adults after a tonsillectomy and the various painkillers used to accommodate post-operation pain.  The study determined that ibuprofen managed the pain just as effectively as any prescription painkiller that has been used in the past.  A common painkiller used was acetaminophen with codeine or acetaminophen with hydrocodone.  Not only was ibuprofen proven just as effective in relieving pain as the prescription medications, but it also proved to be the safest alternative for children.1

 Codeine is an opiate (narcotic) analgesic that changes the way the body senses pain by converting codeine into morphine in the body.3,4  As a result, many children experience side effects such as nausea, emesis, and constipation, especially if the child is a ‘CYP2D6 ultra-rapid codeine metabolizer’. In these patients, codeine is converted into morphine in the body at a faster rate than normal, resulting in high levels of morphine in the blood that can cause toxic effects such as breathing difficulties.4  An article published in the Journal of the American Academy of Physician Assistants reiterated the FDA’s recommendation to avoid using codeine in children after a tonsillectomy due to the risk of respiratory depression, a condition in which there fails to be full ventilation to the lungs.5  For this reason, I would agree with the article that if products containing codeine can be avoided, this would be a better treatment option, especially in children.

Another reason for this consensus is the proven effectiveness of ibuprofen.  A study was done by the Department of Pediatrics at the University of California comparing the effectiveness of acetaminophen with codeine to ibuprofen for children ages 5-17.  It was shown, when measuring pain levels from baseline of both medications, the ibuprofen group was favored because it was just as effective as acetaminophen with codeine without the health risks.6  Indiana University Medical Center also measured post operative pain using a validated pain scale for pediatric patients.  It was determined that ibuprofen is at least as effective as acetaminophen with codeine for post-operative pain control in children.7

As mentioned above, there are many studies in support of the claim made by this US News and Health article.  However, there are also limitations to the article and the claims that it makes.  One limitation is that the article has yet to be published in a peer reviewed medical journal meaning that the quality of the article has not been assessed by an expert journal editor in the field.1  The benefit of a peer-reviewed article is that the reviewer will have checked for validity and rigor as well as made any additional suggestions to the study design.8 However, the study was presented in the annual meeting of the American Academy of Otolaryngology-Head and Neck Surgery in Vancouver, providing a peer review process until it is officially published in a medical review journal.  In addition, the study also stated that, “An over the counter painkiller is as effective as prescription drugs in controlling pain after people have their tonsils removed”.  However, in the following paragraphs, the study only examined the effects in twenty-five children and not in adults.  This causes one to wonder if ibuprofen is just as effective for adults as well, or only in children.  Thus, the results cannot be generalized to the adult population, and only a small sample size was tested creating some additional limitations in the research.1

Nonetheless, the use of ibuprofen is a valid treatment option in place of the standard treatment such as acetaminophen with codeine.  This recommendation will affect the frequency and demand of ibuprofen as an over the counter medication.2  The effectiveness, safety, and limited side effects of ibuprofen make it a good treatment option for pain management following a tonsillectomy for those 6 months and older.6

As US News and Health states, it appears that an over the counter medication such as ibuprofen is just as effective as a prescription painkiller in children following tonsillectomy.  Not only does it provide a cheaper and more convenient treatment option, but it is also a safer approach to treatment, especially in children.1  This leads one to wonder, would a similar treatment approach prove to be just as effective in adults?

 

References

  1. After tonsillectomy, over-the-counter painkillers suffice, study says. US News: Health Web site. http://health.usnews.com/health-news/news/articles/2013/10/03/after-tonsillectomy-over-the-counter-painkillers-suffice-study-says. Published October 3, 2013. Accessed October 10, 2013.
  2. Tonsillitis. Mayo Clinic Web site. http://www.mayoclinic.com/health/tonsillitis/DS00273/DSECTION=treatments%2Dand%2Ddrugs. Published August 4, 2012.  Accessed October 10, 2013.
  3. Codeine. Medline Plus Web site. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682065.html. Published November 11, 2012.  Accessed October 10, 2013.
  4. Restrictions on use of codeine for pain relief in children – CMDh endorses PRAC recommendation. Eurpoean Medicines Agency Web site. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/06/news_detail_001829.jsp&mid=WC0b01ac058004d5c1. Published June 28, 2013.  Accessed October 10, 2013.
  5. DeDea L, Bushardt R. PHARMACOLOGY CONSULT. Codeine and acetaminophen recommendations for children. JAAPA: Journal Of The American Academy Of Physician Assistants (Lippincott Williams & Wilkins) [serial online]. September 2013;26(9):11-12. Available from: CINAHL Plus with Full Text, Ipswich, MA. Accessed October 10, 2013.
  6. Friday J, Kanegaye J, McCaslin I, Zheng A, Harley J. Ibuprofen provides analgesia equivalent to acetaminophen–codeine in the treatment of acute pain in children with extremity injuries: a randomized clinical trial. Academic Emergency Medicine [serial online]. August 2009;16(8):711-716. Available from: CINAHL Plus with Full Text, Ipswich, MA. Accessed October 10, 2013.
  7. St. Charles C. A comparison of ibuprofen versus acetaminophen with codeine in the young tonsillectomy patient . Science Direct. 1997;117(1):76-82.
  8. Evaluating information sources. Lloyd Sealy Library Web site. http://guides.lib.jjay.cuny.edu/content.php?pid=209679&sid=1746812. Published March 25, 2013.  Accessed October 10, 2013.