Ibuprofen


Article Author:
Vincent Trung Ngo


Article Editor:
Tushar Bajaj


Editors In Chief:
David Wood
Andrew Wilt
Hajira Basit


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
9/8/2019 11:01:29 PM

Indications

Ibuprofen is indicated and FDA-approved for use in the treatment of inflammatory diseases and rheumatoid disorders. The discovery of ibuprofen was spurred by finding an alternative non-corticosteroid treatment for rheumatoid arthritis. The disease was the initial impetus for the creation of what would eventually become known as ibuprofen; Dr. Stewart Adams OBE was the researcher whose work would lead to the discovery of the drug. Initially patented as 2-(4-isobutylphenyl) propionic acid in 1961 by Dr. Adams and John Nicholson, ibuprofen became and remains one of the most widely used NSAIDs worldwide.[1] Today, ibuprofen remains a monotherapy for managing of pain in rheumatoid disorders and inflammatory diseases, with a portion of research centered around the creation of novel treatments or drugs. One such study involves the creation of NSAID and carbonic anhydrase inhibitor hybrid drugs for the management of pain in rheumatoid arthritis.[2]

Ibuprofen is also FDA-approved for use in mild to moderate pain. It is also available as an over-the-counter medication for pain, usually mild. Some common over-the-counter uses for ibuprofen are muscle sprains or strains, joint aches, pain from migraine, sore throat, and pain from cold or cases of flu. Some of the current research into the use of ibuprofen as a treatment for various sources of pain typically focuses on comparing treatment efficacy with other NSAIDs, with an emphasis on COX-2 inhibitors, or with novel treatment methods. A study comparing COX-2 inhibitors with ibuprofen after third molar removal showed no statistically significant differences in pain relief after 6, 8, and 12 hours, but a significant increase in rescue analgesia use in the ibuprofen group after 24 hours. Researchers also noted a greater instance of nausea and vomiting in the ibuprofen group.[3] Postoperative pain is an area where ibuprofen has had demonstrated efficacy: In a randomized, double-blind study comparing IV ibuprofen and IV acetaminophen use for postoperative pain treatment in patients who underwent laparoscopic cholecystectomies, IV ibuprofen was shown to have lower pain scores and reduced opioid use in the first 24 hours following procedure compared to acetaminophen.[4] Lastly, a trial focusing on ibuprofen administration along with adjunct medication (baclofen, tizanidine, or metaxalone) or placebo for acute low back pain in an emergency department setting showed no improvement of functioning or pain by one week for any of the adjunct medication groups as compared to placebo.[2] Though ibuprofen is already widely accepted as an effective treatment for pain, research is continually seeking to add more effectiveness to the clinical use of ibuprofen in pain treatment.

Ibuprofen is also an FDA-approved antipyretic, used for fever reduction in both adults and children. The use of NSAIDs in treating fever is much more commonplace in pediatric patients, and much contemporary research centers around creating more efficacy in the usage of ibuprofen in treating pediatric fever. A literature review in 2017 showed little evidence to suggest superior efficacy between either ibuprofen or paracetamol in the treatment of fever. Six studies evaluated in the review showed a marginal difference with ibuprofen, but data remained insufficient to state ibuprofen as producing better outcomes.[5] In a related study, refractory fevers responded more favorably to alternating acetaminophen and ibuprofen dosing compared with monotherapy of either, but only in those patients who respond positively after the first cycle.[6]

Dysmenorrhea is a medical condition involving pain during menstruation, which may vary in quality and timing. Dysmenorrhea may be either primary, which is usually mediated by prostaglandin production during ovulation, or secondary from another disease such as endometriosis or pelvic inflammatory disease.[7] NSAIDs are often a therapeutic choice, and FDA-approved to treat primary dysmenorrhea. A study exploring the use of cinnamon as an alternative treatment for primary dysmenorrhea study showed beneficial effects for pain reduction when compared with placebo, but a weaker effect than ibuprofen.[8] Transdermal drug delivery has been a topic of research in the context of ibuprofen and primary dysmenorrhea; a study investigated the use of essential oils as penetration enhancers for transdermal delivery of ibuprofen in patients with dysmenorrhea. This study was motivated by the known risk of GI bleeding and ulceration after oral NSAID usage and sought to investigate a potentially efficacious method of delivery that would decrease these risks. The study found that one of the essential oils, chuanxiong oil, did have positive effects on permeation and pain alleviation when administered with ibuprofen hydrogel.[9]

Ibuprofen and other NSAIDs are also FDA-approved to treat osteoarthritis, often after non-pharmacological measures such as weight loss and strengthening exercises are used. Adjunct medication usage has been explored, with a study showing promise with enhanced outcomes using acupuncture alongside topical ibuprofen compared with topical ibuprofen alone in patients with chronic knee pain due to osteoarthritis.[10] A comparative study between celecoxib and ibuprofen showed equal tolerance and efficacy between the two in the treatment of patients with knee osteoarthritis.[11]

The use of ibuprofen for treatment of gout attacks or flares has been long-researched, with Schweitz et al. in 1978 demonstrating the rapid improvement and symptom resolution in 10 patients with acute gouty arthritis after being treated with 2400 mg of ibuprofen.[12] NSAIDs are commonly used as monotherapy for mild flares, and with colchicine as dual therapy for moderate or severe flares. Treatment of acute gout flares is an off-label use for ibuprofen.

NSAIDs and colchicine are also often used in the treatment of pericarditis, owing to NSAID’s anti-inflammatory and analgesic properties. Ibuprofen is one of the more well-documented NSAIDs in the treatment of pericarditis, with research into its effectiveness in treating and preventing multiple recurrences of idiopathic pericarditis compared with aspirin done in the CORP and CORP-2 trials starting in 2011. Findings showed no significant difference between treatment or prevention of idiopathic pericarditis between the two drugs.[13] Colchicine was shown in a 2014 review to be effective in reducing instances of recurrent pericarditis when used as adjunctive therapy to NSAIDs such as ibuprofen, aspirin, or indomethacin, but with limitations in the number of trials and the statistical power of said trials.[14] Treatment of pericarditis with ibuprofen is an off-label use.

Intravenous ibuprofen has been FDA-approved for the closure of patent ductus arteriosus (PDA) in premature infants and has demonstrated to be as effective as indomethacin in treating PDA. Differences exist in the amount of systemic vasoconstriction and renal toxicity; likely due to less COX-1 selectivity, ibuprofen has been shown to have decreased rates of both outcomes.[15]

Since 2007, the USPSTF has recommended the use of aspirin and NSAIDs in preventing colorectal cancer in specific populations. In 2016, they updated this statement along with their 2009 statement for aspirin and NSAID use in preventing cardiovascular disease.[16] Although the recommendations are not for ibuprofen specifically, they still suggest a strong foundation of research that supports a potentially greater role of NSAIDs in the treatment and prevention of cancer. Burgeoning research on the efficacy of NSAIDs in the realm of cancer treatment, with some research specifically on the efficacy of ibuprofen, has shown promise. A review by Hil’ovska et al. showed potential uses for NSAIDs in reducing cancer cell growth, movement, and invasion; in the induction of cancer cell-death; and in facilitating a lower dose of cytotoxic drug usage.[17] The studies reviewed primarily focused on COX-2 inhibitors. For ibuprofen specifically, some studies have suggested a stronger anticancer effect than aspirin against breast and lung cancer,[18] as well as a reduction in the risk of breast cancer with ibuprofen or aspirin use.[19]

Similarly, Wawro et al. have shown a potential indication for NSAID use, particularly aspirin and ibuprofen, during cancer treatment in colorectal cancer patients who are undergoing vincristine monotherapy. The purported role of NSAIDs is primarily in preventing chemoresistance by inhibiting proliferation of cancer-associated fibroblast formation. Vincristine stimulates the growth of cancer-associated fibroblasts via the secretion of tumor growth factors beta and interleukin-6; the researchers saw an inhibitive effect on this process with aspirin and ibuprofen usage. Their research purports that the likely mechanism behind this involves NSAIDs affecting the rate of regulation of microtubule polymerization.[20]

Mechanism of Action

The primary mechanism of Ibuprofen, an NSAID, is through the inhibition of prostaglandin precursors. After a physiological or pathological stimulus, membrane phospholipids release arachidonic acid due to the enzyme phospholipase A2. Arachidonic acid then undergoes passage into one of three different enzymatic pathways: cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450). The cyclooxygenase pathway converts arachidonic acid to prostaglandins, prostacyclins, and thromboxanes. The lipoxygenase pathway yields hydroxyeicosatetranoic acids (HETEs), leukotrienes, and lipoxins from arachidonic acid metabolism. Lastly, arachidonic acid converts to HETEs and epoxyeicosatrienoic acids (EET) via the cytochrome P450 pathway.[17]

These metabolic pathways all create products referred to as eicosanoids, which are molecules that are involved in the intercellular and intracellular signaling processes of a variety of physiological processes: smooth muscle tone regulation, vascular permeability, transporter proteins, platelet aggregation, and cell proliferation. As in the case of cyclooxygenase pathway products, eicosanoids also have involvement in autoimmunity, angiogenesis, atopy, inflammation, and cancer.[21]

In terms of the current indicated uses of ibuprofen, the cyclooxygenase pathway plays a prominent role. There are three distinct isoforms in the COX pathway: COX-1 (PGH synthase), COX-2, and COX-3. COX-1 is a constitutionally expressed isoform, with levels relatively stable in reaction to most physiologic or pathologic stimuli. In contrast, COX-2 expression is highly inducible by mitogenic and inflammatory stimuli. Among these, the more well-known are transforming growth factor, fibroblast growth factor, vascular endothelial growth factor, and tumor necrosis factors. The function of COX-3 isoform is still largely unknown and remains a topic of contemporary research.[22][17] Inhibition of COX-1 and COX-2 pathways decreases the expression of prostaglandin precursors; this, in turn, lessens the degree of cellular response to pathologic or physiologic stimuli. It is by this mechanism that non-selective NSAIDs such as Ibuprofen derive their analgesic, antipyretic, and anti-inflammatory properties.[17] For ibuprofen specifically, COX-1 is inhibited approximately 2.5 times more potently than COX-2, which suggests implications into much research of the comparative efficacy of COX-2 selective inhibitors in treating diseases normally treated with ibuprofen.[13]

COX-2 aside from its well-known roles in inflammation has also been found to get constitutively expressed during early carcinogenesis.[8] Research has noted higher levels of COX-2 have demonstrated in several human tumors, including breast, colorectal, esophageal, lung, and pancreatic.[17] The current findings on COX-2 and its various effects on cells suggest that the anticancer effects of NSAIDs, such as Ibuprofen are due to COX-2 inhibition. Though the anticancer effects of COX-2 inhibition are well-documented, there is still some question as to the exact mechanism by which this occurs. Moreover, there is also evidence that other pathways may be involved in the anticancer and antitumor effects of NSAIDs, due to NSAID reducing cell survival in both COX-2 overexpressed as well as COX-2 deficient malignant cells.[23]

For the other two enzymatic pathways, a sizeable amount of research on their potential involvement in carcinogenesis has been conducted, but the information is still limited. LOX isoforms, particularly 5-LOX, 12-LOX, and 15-LOX, have been discussed as potential contributors to tumor development and growth. 5-LOX is normally expressed only in immune cells and has been implicated in the early stages of colon cancer, carcinogenesis in oral cavity tissue, and the expression of chronic myeloid leukemia.[24][25][26] 12-LOX has proangiogenic functions, as it controls G1/S-phase arrest via a dual process: regulation of Nf-kB, and inhibition of Akt and mitogen-activated protein kinases.[10] 15-LOX isoforms promote cell senescence and suppress cell cycle progression.[27]

Administration

Ibuprofen, an over-the-counter drug in most countries, is available in forms convenient for consumer consumption. Typical dosage formulations include oral capsule, oral suspension, oral tablet, chewable tablet, intravenous solution, topical gel, and combination kit. The recommendation with oral administration is usually to consume the drug with food or milk in both adults and children. IV administration is often an option in inpatient settings for convenience of delivery or when oral delivery is unavailable,[15][4] and infusion should be over at least 30 minutes for adults, and 10 minutes in pediatric patients. Ibuprofen with lysine is a commonly used IV formulation. Ibuprofen should not be administered simultaneously with total parenteral nutrition but may still use the same line, pausing total parenteral nutrition for 15 minutes before and after ibuprofen dosing. Burgeoning research is hoping to further explore the possibility of simultaneous delivery of ibuprofen with other IV medications or nutrition. A recent study exploring the chemical compatibility of continuous ibuprofen lysine infusion with total parenteral nutrition was conducted recently in 2018, which showed both physical and chemical compatibility of IV ibuprofen infusion with two different total parenteral nutrition formulations in neonates with PDA.[28] Topical application of ibuprofen is also currently under research as a more efficient means of treating diseases known to be susceptible to ibuprofen, such as osteoarthritis and dysmenorrhea.[9][29]

Adverse Effects

Gastrointestinal bleeding is a well-known adverse effect of ibuprofen usage and can lead to gastritis, ulceration, hemorrhage, or perforation. Inhibition of COX isoforms in ibuprofen usage leads to the reduction of prostaglandins, which play a role in the secretion of gastroprotective mucus.[30] This effect is more pronounced in non-selective NSAIDs, with COX-2 selective NSAIDs having a lower incidence of gastrointestinal complications, which is of particular concern in children, for which the use of ibuprofen is higher than other NSAIDs due to its comparative safety compared to other drugs in its class. Usage of ibuprofen over-the-counter without medical consultation also increases the risk of high dosage levels and short-term interval dosing that may precipitate gastrointestinal complications.[31]

Diminished renal function is also a concern with ibuprofen usage, with a recent surveillance study showing NSAIDs having nephrotoxic properties even in patients with no deficit in kidney function.[32] Dehydration is a common risk factor in ibuprofen-induced renal injury, and as such much research has taken place regarding NSAIDs and kidney function in populations more vulnerable to dehydration, such as children with renal comorbidities or endurance athletes. A double-blind placebo-controlled trial in a population of ultramarathon participants showed an increased rate of acute kidney injury in those who took ibuprofen, with a number needed to harm of 5.5.[33] Consideration of a patient’s renal function is necessary when weighing treatment with ibuprofen or other NSAIDs.

Rashes are also a known adverse effect of ibuprofen usage, usually due to drug hypersensitivity or skin irritation via topical administration. A rash may also be part of a more severe syndrome caused by ibuprofen use, such as anaphylaxis or drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. A case in 2016 reported a rare instance of DRESS syndrome, which causes skin, liver, and hematologic abnormalities, with ibuprofen use in a pediatric patient. DRESS syndrome is known to result more commonly with anticonvulsants, sulfa derivatives, and antimicrobials, and the number of known cases related to ibuprofen is limited. The etiology of DRESS syndrome is also unknown, with theories focusing on hypersensitivity to toxic metabolites or pathology involving human herpesvirus-6 currently postulated.[34] Other cases have existed in the literature of similar severe drug reactions involving ibuprofen or other NSAIDs; another case report in 2014 detailed a patient who developed drug-induced liver injury with multiform exudative erythema after ingestion of an over-the-counter medication containing ibuprofen for 20 days.[35]

The association between hypertension and NSAID use has undergone research previously. A cross-sectional study of an elderly population in 1993 showed NSAID usage to be an independent risk factor in the development of hypertension in this population.[36] Studies since then have pursued more knowledge on NSAIDs in the context of hypertension, such as investigating for comparative differences between NSAIDs. A retrospective cohort study in 2012 showed an association with a small increase in systolic blood pressure with NSAIDs compared to acetaminophen use, particularly ibuprofen. This effect was negligible, though, in patients prescribed diuretics or multiple antihypertensives.[37]

Intravenous ibuprofen in the treatment of patent ductus arteriosus (PDA) has shown an increased incidence of hyperbilirubinemia, as well as bilirubin-displacement due to the high protein binding of the medication.[38]

Contraindications

Ibuprofen use is contraindicated in patients with a known history of hypersensitivity or allergic reactions to the drug itself, other NSAIDs, or aspirin. Numerous case studies detail ibuprofen as a precipitant of disease after usage.[34][35] NSAIDs as a class are among the most frequently associated with hypersensitivity reactions for both adult and pediatric populations, with the most frequent diagnoses being urticaria/angioedema caused by cross-intolerance to other drug classes, namely quinolones and amoxicillin-clavulanic acid.[39] Research done on NSAID-induced hypersensitivity reactions in the pediatric population showed similar prevalence but differences in the clinical phenotypes. Oral provocation testing is still the gold standard for diagnosis of NSAID hypersensitivity, and safe alternatives for cross-intolerant children and adolescents exist, including tolmetin, etoricoxib, paracetamol, and nimesulide.[40]

In preterm neonates, ibuprofen lysine IV formulation is contraindicated in those with congenital heart diseases which require patency of the PDA, active bleeding, thrombocytopenia, renal impairment, coagulation defects, and proven or suspected necrotizing enterocolitis. Aside from this, ibuprofen use has been shown not to have any increased adverse effects when used in infants younger than six months and is still indicated for use in pediatric populations outside of these contraindications.[39]

In Canada, ibuprofen has contraindications listed on drug labels for additional conditions, including active GI or cerebrovascular bleeding, uncontrolled heart failure, lupus, renal impairment, and hepatic impairment or disease. 

Monitoring

For patients who use ibuprofen, appropriate monitoring should seek to minimize the possibility of common and uncommon adverse effects. Pain relief and gastrointestinal symptoms should be included in a patient’s clinical evaluation because they may suggest desensitization to the analgesic effect of ibuprofen or emerging gastritis or GI bleed. Blood pressure should also be monitored, especially in the elderly or hypertensive population.[36][37] Renal function monitoring is also a recommendation, as NSAIDs are known to be nephrotoxic in at-risk populations as well as individuals with normal baseline renal function.[32][33] Liver function is typically not monitored in patients who use ibuprofen, but cases of NSAID-induced livery injury in pediatric populations may suggest the need for monitoring in individuals with high-risk factors or at-risk populations. Though the much less frequent than acetaminophen, cases of NSAID-induced liver damage have occurred in past reports; unlike acetaminophen-induced liver injury, there is no antidote for liver damage due to NSAID use.[41] The increasing frequency of ibuprofen use in children points to a potential focus for further research on NSAID in the context of liver function.

Toxicity

Ibuprofen’s potential for toxicity in the body derives from the various cellular processes throughout multiple organ systems that are affected by the inhibition of the cyclooxygenase pathway. Prostaglandins and thromboxanes play important roles in maintaining the gastric mucosal layer and renal blood flow; though relatively small, ibuprofen still carries a risk of adverse gastrointestinal and renal events even at therapeutic levels. Overdose is a common reason for patient presentation with ibuprofen toxicity, with ibuprofen being the most common NSAID involved in an overdose at 29% with either exclusive use or use in combination with other analgesics.[42]

A risk score has been created by a study which sought to improve the risk-benefit ratio of NSAID usage; Their risk score was accurate in categorizing the one-year risk of major toxicity among NSAID users, with implications towards the utility in further aiding safe treatment of patients using NSAIDs.[43]

Reye syndrome is an increasingly rare phenomenon in modern times, in large part due to efforts by countries to curb aspirin usage beginning on the 1980s. The decreased usage of aspirin in children in the United Kingdom led to a decrease in the incidence of Reye syndrome, from 100 cases in 1984 to 3 cases in 2000.[41] NSAIDs are hepatotoxic and although rare, may precipitate Reye syndrome due to causing the same type of mitochondrial membrane damage.[44] Furthermore, much of the mechanism behind the effect of NSAIDs effect on liver function remains largely unknown. Due to the increasing use of ibuprofen in children, the focus should be on the possibility of a rise in the increasing frequency of drug-induced liver damage and Reye syndrome.[41]

Much like other widely used medications, there is increasing concern about the presence of ibuprofen in the environment as well as the long-term effects of environmental ibuprofen exposure. Studies currently show potential methods of bioremediation of ibuprofen in the atmosphere via bacterial strains,[45] mineral particles, and solar radiation.[46] The toxicity of ibuprofen’s degradation products has also been shown to be minimal compared to ibuprofen’s toxicity. Furthermore, studies have shown a low amount of toxicity towards tested organisms and no mutagenic activity of the drug. There is still a concern, however, for any possible indirect influence environmental ibuprofen may have on prostaglandin-regulated processes, such as ovulation, menstruation, inflammation, and pain.[45][46]

Enhancing Healthcare Team Outcomes

Ibuprofen benefits highly from interprofessional collaboration in its use on patients. There is an abundance of well-reviewed, large studies detailing ibuprofen’s indications for usage in various clinical scenarios. Successful usage of the medication in clinical practice will include knowledge of the latest clinical research, a thorough understanding of the patient, and realistic treatment goals based on current evidence for support. The patient’s primary physician, nursing staff, and pharmacist, all collaborating and ensuring the highest quality of care in a patient for which ibuprofen is part of the treatment regimen, will lead his team in a collaborative effort to ensure successful usage of the medication through these principles:   

  • Administer ibuprofen for the recommended FDA-approved and off-label indications while keeping in mind contraindications or risk factors that may lead to adverse effects.
  • Make a note of any stated over-the-counter ibuprofen use by a patient during a clinical encounter, being diligent in asking for frequency and dosage of usage. Nursing can play a crucial role in obtaining this information and reporting it to the physician.
  • Ask about ibuprofen use in patients with suspected gastritis or ulceration, anemia, or thrombocytopenia.
  • Include ibuprofen in consideration of a toxic agent when treating patients who have overdosed on an unknown substance.
  • Use ibuprofen for mild to moderate pain control in patients with pain as a primary diagnosis or for symptom control.[2][4][8][9][11] [Level II]
  • NSAIDs, including ibuprofen, have shown potential as anticancer agents and should be considered in cancer treatment regimens where appropriate and supported by current research.
  • The use of aspirin and NSAIDs is recommended to prevent colorectal cancer as well as cardiovascular disease.
  • Appropriate monitoring of a patient’s pain level, emerging GI complaints, blood pressure, and renal function will reduce the risk of adverse effects of medication.[33][37] [Level II] Here again, nursing can make a strong contribution in this regard.
  • In pediatric patients, alternating acetaminophen and ibuprofen therapies can be more effective in the reduction of refractory fever than ibuprofen monotherapy alone.[6] [Level I]
  • Usage of ibuprofen to close PDA in neonates is equally as efficacious as indomethacin, with less renal toxicity and systemic vasoconstriction.[15] [Level II] Pediatric/neonatal specialty nurses and pediatric specialty pharmacists should collaborate to ensure safe administration.
  • Intravenous Ibuprofen is physical and chemically compatible with specific formulations of total parenteral nutrition and can be given simultaneously in neonates with PDA.[28] [Level II]
  • Ibuprofen or aspirin should be given with colchicine for effective relief of acute pericarditis as well as reduction of recurrent pericarditis.[13] [Level III]

Being aware of these current evidence-based principles of ibuprofen use can help increase health outcomes for the patient in a collaborative, multidisciplinary healthcare environment. The typical patient who will need to be prescribed ibuprofen and monitored for use will benefit the most from the enhancement of collaborative efforts, as will patients who interact with the healthcare system in multiple settings on a regular basis. Just because ibuprofen has been around for many years does not mean an interprofessional approach is not necessary to optimize therapy and minimize adverse reactions. [Level V]


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Ibuprofen - Questions

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NSAIDs are among the most frequently associated with hypersensitivity reactions for both adult and pediatric populations. What is the gold standard for diagnosis of NSAID hypersensitivity?



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A patient who is taking ibuprofen for osteoarthritis comes to his family practice clinic for a follow-up visit. He has been using ibuprofen as needed for his osteoarthritis and has noticed significant symptoms improvement, but also noticed having some stomach issues. The patient states that he has been having heartburn more frequently now with the use of ibuprofen. He is switched to celecoxib instead. What is the reasoning behind this medication switch?



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A 55-year-old male with major depressive disorder with psychotic features is examined in an inpatient psychiatric ward. He was admitted yesterday after an attempted suicide via acetaminophen ingestion. Emergency services were called when the patient's wife found him on the bathroom floor next to an empty medication bottle. According to the patient's wife, over the last month, the patient had been going through some difficulties with work and with his estranged son. On the inpatient unit, he was started again on his home medications of fluoxetine, risperidone, and ibuprofen. During his recent admission, the laboratory results showed microcytic, hypochromic anemia, and increased red blood cell distribution width. What is the most likely cause of his anemia?



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A 30-year-old patient comes into your clinic complaining of a sudden onset of chest pain. The patient states that he woke up this morning and felt a sharp pain in his chest that increased whenever he took a breath. The patient is otherwise healthy except for a viral illness 2 weeks ago for which he took over-the-counter antihistamines and Tylenol. He denies any history of the streptococcal throat infection. The patient has not traveled outside of the country in recent years and has never had a positive PPD test. A scratching sound on his chest is heard on chest auscultation. Vital signs are within normal limits. The patient denies any fevers, chills, shortness of breath, or palpitations. A stat EKG in the clinic shows diffuse ST elevations. A chest x-ray is unremarkable with no effusions. What is the next best step in management?



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COX inhibition is a principle commonality between the numerous types of NSAIDs. Which of the following NSAIDs reversibly inhibits COX-1 and COX-2 enzymes at therapeutic concentrations?



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A mother comes to an urgent care clinic with her 3-year-old child for fever, rhinorrhea, myalgia, and cough from the last 2 days ago. According to the mother, the child started coughing with a fever 2 days ago after returning from a water-themed park. The mother denies any diarrhea or sputum production. On physical exam, there is a tired-appearing child with rhinorrhea and congestion with intermittent coughing. There is point tenderness on the maxillary sinuses. Lungs are clear to auscultation Temperature is 98.7 degrees. The mother mentions that she has been giving her child ibuprofen to relieve the fever. Which of these statements is true concerning ibuprofen?



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A 65-year-old patient is seen in the ER with substernal chest pain for the last 4 hours. The patient describes the pain as crushing, radiating to his left jaw, and not affected by position changes. The patient states that he has never had this type of pain before. Three days ago, the patient slipped and fell while stepping off of a street curb, and sprained his left ankle. He has a history of ischemic R ACA stroke with residual deficits in his left foot with a slight foot drop. The patient had been taking aspirin for his past stroke and was also recently taking another pain medication for his ankle sprain. Physical exam shows a diaphoretic man clutching his chest, with his left ankle in a soft cast. Cardiac marker labs show elevated troponin, with ECG showing no irregularities. What is the most likely medication this patient was taking in addition to the aspirin?



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A 45-year-old male presents complaining of tiredness and fatigue for the past month. He has a history of lumbosacral muscle strain for which he takes ibuprofen as needed for pain control. He states that he hurt his back two months ago while lifting weights, and has been taking ibuprofen regularly for pain relief. He is otherwise healthy, continues to be active, and takes no other medication. He has followed a vegan diet for the past year. Physical exam shows mild conjunctival pallor. Patient denies any recent unexplained weight loss or frank blood per rectum but has noticed he has dark stools intermittently. Family history is unremarkable. CBC shows a microcytic anemia with increased red cell distribution width. A fecal occult blood test is positive. What is the most likely underlying cause of this patient's chief complaint?



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Ibuprofen - References

References

Halford GM,Lordkipanidzé M,Watson SP, 50th anniversary of the discovery of ibuprofen: an interview with Dr Stewart Adams. Platelets. 2012;     [PubMed]
Akgul O,Di Cesare Mannelli L,Vullo D,Angeli A,Ghelardini C,Bartolucci G,Alfawaz Altamimi AS,Scozzafava A,Supuran CT,Carta F, Discovery of Novel Nonsteroidal Anti-Inflammatory Drugs and Carbonic Anhydrase Inhibitors Hybrids (NSAIDs-CAIs) for the Management of Rheumatoid Arthritis. Journal of medicinal chemistry. 2018 Jun 14;     [PubMed]
González-Barnadas A,Camps-Font O,Martín-Fatás P,Figueiredo R,Gay-Escoda C,Valmaseda-Castellón E, Efficacy and safety of selective COX-2 inhibitors for pain management after third molar removal: a meta-analysis of randomized clinical trials. Clinical oral investigations. 2019 Apr 23;     [PubMed]
Ekinci M,Ciftci B,Celik EC,Köse EA,Karakaya MA,Ozdenkaya Y, A Randomized, Placebo-Controlled, Double-Blind Study that Evaluates Efficacy of Intravenous Ibuprofen and Acetaminophen for Postoperative Pain Treatment Following Laparoscopic Cholecystectomy Surgery. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2019 Apr 22;     [PubMed]
Narayan K,Cooper S,Morphet J,Innes K, Effectiveness of paracetamol versus ibuprofen administration in febrile children: A systematic literature review. Journal of paediatrics and child health. 2017 Aug;     [PubMed]
Luo S,Ran M,Luo Q,Shu M,Guo Q,Zhu Y,Xie X,Zhang C,Wan C, Alternating Acetaminophen and Ibuprofen versus Monotherapies in Improvements of Distress and Reducing Refractory Fever in Febrile Children: A Randomized Controlled Trial. Paediatric drugs. 2017 Oct;     [PubMed]
Durain D, Primary dysmenorrhea: assessment and management update. Journal of midwifery     [PubMed]
Jaafarpour M,Hatefi M,Khani A,Khajavikhan J, Comparative effect of cinnamon and Ibuprofen for treatment of primary dysmenorrhea: a randomized double-blind clinical trial. Journal of clinical and diagnostic research : JCDR. 2015 Apr;     [PubMed]
Chen J,Jiang QD,Wu YM,Liu P,Yao JH,Lu Q,Zhang H,Duan JA, Potential of Essential Oils as Penetration Enhancers for Transdermal Administration of Ibuprofen to Treat Dysmenorrhoea. Molecules (Basel, Switzerland). 2015 Oct 7;     [PubMed]
Gordo AC,Walker C,Armada B,Zhou D, Efficacy of celecoxib versus ibuprofen for the treatment of patients with osteoarthritis of the knee: A randomized double-blind, non-inferiority trial. The Journal of international medical research. 2017 Feb;     [PubMed]
Schweitz MC,Nashel DJ,Alepa FP, Ibuprofen in the treatment of acute gouty arthritis. JAMA. 1978 Jan 2;     [PubMed]
Schwier N,Tran N, Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis. Pharmaceuticals (Basel, Switzerland). 2016 Mar 23;     [PubMed]
Bayes-Genis A,Adler Y,de Luna AB,Imazio M, Colchicine in Pericarditis. European heart journal. 2017 Jun 7;     [PubMed]
Ferguson JM, Pharmacotherapy for patent ductus arteriosus closure. Congenital heart disease. 2019 Jan;     [PubMed]
Bibbins-Domingo K, Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of internal medicine. 2016 Jun 21;     [PubMed]
Hiľovská L,Jendželovský R,Fedoročko P, Potency of non-steroidal anti-inflammatory drugs in chemotherapy. Molecular and clinical oncology. 2015 Jan;     [PubMed]
Harris RE,Beebe-Donk J,Doss H,Burr Doss D, Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (review). Oncology reports. 2005 Apr;     [PubMed]
Cuzick J,Otto F,Baron JA,Brown PH,Burn J,Greenwald P,Jankowski J,La Vecchia C,Meyskens F,Senn HJ,Thun M, Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. The Lancet. Oncology. 2009 May;     [PubMed]
Wawro ME,Sobierajska K,Ciszewski WM,Niewiarowska J, Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation. International journal of molecular sciences. 2019 Apr 20;     [PubMed]
Harizi H,Corcuff JB,Gualde N, Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends in molecular medicine. 2008 Oct;     [PubMed]
Kis B,Snipes JA,Busija DW, Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties. The Journal of pharmacology and experimental therapeutics. 2005 Oct;     [PubMed]
Zhang X,Morham SG,Langenbach R,Young DA, Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase-null embryo fibroblasts. The Journal of experimental medicine. 1999 Aug 16;     [PubMed]
Wasilewicz MP,Kołodziej B,Bojułko T,Kaczmarczyk M,Sulzyc-Bielicka V,Bielicki D,Ciepiela K, Overexpression of 5-lipoxygenase in sporadic colonic adenomas and a possible new aspect of colon carcinogenesis. International journal of colorectal disease. 2010 Sep;     [PubMed]
Metzger K,Angres G,Maier H,Lehmann WD, Lipoxygenase products in human saliva: patients with oral cancer compared to controls. Free radical biology     [PubMed]
Chen Y,Hu Y,Zhang H,Peng C,Li S, Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia. Nature genetics. 2009 Jul;     [PubMed]
Terada N,Shimizu Y,Kamba T,Inoue T,Maeno A,Kobayashi T,Nakamura E,Kamoto T,Kanaji T,Maruyama T,Mikami Y,Toda Y,Matsuoka T,Okuno Y,Tsujimoto G,Narumiya S,Ogawa O, Identification of EP4 as a potential target for the treatment of castration-resistant prostate cancer using a novel xenograft model. Cancer research. 2010 Feb 15;     [PubMed]
Tang DG,Bhatia B,Tang S,Schneider-Broussard R, 15-lipoxygenase 2 (15-LOX2) is a functional tumor suppressor that regulates human prostate epithelial cell differentiation, senescence, and growth (size). Prostaglandins     [PubMed]
Garcia J,Garg A,Song Y,Fotios A,Andersen C,Garg S, Compatibility of intravenous ibuprofen with lipids and parenteral nutrition, for use as a continuous infusion. PloS one. 2018;     [PubMed]
Liu SC,Qiao XF,Tang QX,Li XG,Yang JH,Wang TQ,Xiao YJ,Qiao JM, A retrospective study of acupuncture as an adjunctive therapy to topical ibuprofen for chronic knee pain due to osteoarthritis. Medicine. 2019 Apr;     [PubMed]
Rafaniello C,Ferrajolo C,Sullo MG,Sessa M,Sportiello L,Balzano A,Manguso F,Aiezza ML,Rossi F,Scarpignato C,Capuano A, Risk of gastrointestinal complications associated to NSAIDs, low-dose aspirin and their combinations: Results of a pharmacovigilance reporting system. Pharmacological research. 2016 Feb;     [PubMed]
Mărginean MO,Meliț LE,Mocanu S,Săsăran V, Ibuprofen, a Potential Cause of Acute Hemorrhagic Gastritis in Children - A Case Report. Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures). 2018 Oct;     [PubMed]
Balestracci A,Ezquer M,Elmo ME,Molini A,Thorel C,Torrents M,Toledo I, Ibuprofen-associated acute kidney injury in dehydrated children with acute gastroenteritis. Pediatric nephrology (Berlin, Germany). 2015 Oct;     [PubMed]
Lipman GS,Shea K,Christensen M,Phillips C,Burns P,Higbee R,Koskenoja V,Eifling K,Krabak BJ, Ibuprofen versus placebo effect on acute kidney injury in ultramarathons: a randomised controlled trial. Emergency medicine journal : EMJ. 2017 Oct;     [PubMed]
Koca T,Akcam M, Ibuprofen induced DRESS Syndrome in a Child. Indian pediatrics. 2016 Aug 8;     [PubMed]
Watanabe T,Abe M,Tada F,Aritomo K,Ochi H,Koizumi Y,Tokumoto Y,Hirooka M,Kumagi T,Ikeda Y,Matsuura B,Hiasa Y, Drug-induced liver injury with serious multiform exudative erythema following the use of an over-the-counter medication containing ibuprofen. Internal medicine (Tokyo, Japan). 2015;     [PubMed]
Johnson AG,Simons LA,Simons J,Friedlander Y,McCallum J, Non-steroidal anti-inflammatory drugs and hypertension in the elderly: a community-based cross-sectional study. British journal of clinical pharmacology. 1993 May;     [PubMed]
Aljadhey H,Tu W,Hansen RA,Blalock SJ,Brater DC,Murray MD, Comparative effects of non-steroidal anti-inflammatory drugs (NSAIDs) on blood pressure in patients with hypertension. BMC cardiovascular disorders. 2012 Oct 24;     [PubMed]
Thibaut C,Hazard A,Huon C,Desfrere L, Effect of ibuprofen on bilirubin-albumin binding during the treatment of patent ductus arteriosus in preterm infant. The journal of maternal-fetal     [PubMed]
Cavkaytar O,du Toit G,Caimmi D, Characteristics of NSAID-induced hypersensitivity reactions in childhood. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2019 Feb;     [PubMed]
Walsh P,Rothenberg SJ,Bang H, Safety of ibuprofen in infants younger than six months: A retrospective cohort study. PloS one. 2018;     [PubMed]
Norman H,Elfineh M,Beijer E,Casswall T,Németh A, [Also ibuprofen, not just paracetamol, can cause serious liver damage in children. NSAIDs should be used with caution in children, as shown in case with fatal outcome]. Lakartidningen. 2014 Oct 1-7;     [PubMed]
Ershad M,Vearrier D, Ibuprofen Toxicity 2019 Jan;     [PubMed]
Solomon DH,Shao M,Wolski K,Nissen S,Husni ME,Paynter N, Derivation and Validation of a Major Toxicity Risk Score Among NSAID Users Based on Data from a Randomized Controlled Trial. Arthritis     [PubMed]
Jaeschke H,McGill MR,Ramachandran A, Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity. Drug metabolism reviews. 2012 Feb;     [PubMed]
Marchlewicz A,Guzik U,Hupert-Kocurek K,Nowak A,Wilczyńska S,Wojcieszyńska D, Toxicity and biodegradation of ibuprofen by Bacillus thuringiensis B1(2015b). Environmental science and pollution research international. 2017 Mar;     [PubMed]
Rubasinghege G,Gurung R,Rijal H,Maldonado-Torres S,Chan A,Acharya S,Rogelj S,Piyasena M, Abiotic degradation and environmental toxicity of ibuprofen: Roles of mineral particles and solar radiation. Water research. 2018 Mar 15;     [PubMed]

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