{"id":3372,"date":"2018-02-01T00:00:41","date_gmt":"2018-02-01T05:00:41","guid":{"rendered":"https:\/\/rhochistj.org\/RhoChiPost\/?p=3372"},"modified":"2018-09-30T08:53:36","modified_gmt":"2018-09-30T13:53:36","slug":"acetaminophen-toxicity-and-n-acetylcysteine","status":"publish","type":"post","link":"https:\/\/rhochistj.org\/RhoChiPost\/acetaminophen-toxicity-and-n-acetylcysteine\/","title":{"rendered":"Acetaminophen toxicity and n-acetylcysteine"},"content":{"rendered":"<p><b><i>By: <\/i><\/b><b><i>Kathleen Horan, PharmD Candidate c\/o 2020<\/i><\/b><\/p>\n<p>&#8211;<\/p>\n<p>During my institutional Introductory Pharmacy Practice Experiential (IPPE) rotation in the emergency department at NYU Winthrop University Hospital in the spring of 2018, I witnessed a variety of interesting cases while shadowing my preceptor, emergency department pharmacist Megan Czuba, PharmD. Among these emergencies cases, I witnessed a patient experiencing an acetaminophen overdose and was surprised by the gravity of effects that a toxicity caused by such a commonly used medication can have on a patient. After the patient had been stabilized using the widely accepted antidote discussed below, N-Acetylcysteine, my preceptor explained the prevalence of this toxicity as well as other possible treatments available to patients who are afflicted by this toxicity with emphasis on the fact that pharmacists and student pharmacists alike should be aware of the effects that seemingly harmless medications like acetaminophen can have when taken in large doses.<\/p>\n<p>Acetaminophen is the most commonly used analgesic-antipyretic in the United States.\u00a0 It is found not only in common over-the-counter products, such as Tylenol\u00ae, FeverAll\u00ae, and Mapap\u00ae, but also in several over-the-counter and prescription combination products, such as Excedrin\u00ae, NyQuil\u2122, Fioricet\u00ae, Norco\u00ae, and Vicodin\u00ae.\u00a0 Because of its prevalence and use in many combination products, it can be easy for patients to accidentally take too much acetaminophen without realizing it.\u00a0 People also sometimes take a high dose of acetaminophen to attempt suicide.<sup>1<\/sup><\/p>\n<p>Acute acetaminophen overdose is defined as a single ingestion of the drug which occurs within a single 8-hour period. The lowest acute doses found to be capable of causing toxicity are 7.5g in an adults and 150mg\/kg in children.\u00a0 However, these are relatively conservative standards and it is likely that the actual dose needed to cause toxicity is higher.<sup>2<\/sup><\/p>\n<p>Acetaminophen overdose leads to acetaminophen toxicity, which causes serious health problems and can even lead to death.\u00a0 Some people affected by acetaminophen toxicity are asymptomatic.\u00a0 In symptomatic patients, the symptoms follow a pattern depending on the length of time since overdose.\u00a0 Symptoms in the first 24 hours may include feeling tired and sick, sweating, paleness, nausea, and vomiting.\u00a0 On the second and third day, the symptoms from the first day may go away, however, it is during this time that the liver or kidneys may stop working correctly.\u00a0 Some symptoms during this period include belly pain and decreased urination.\u00a0 After the third day, the original symptoms may return, accompanied by confusion and jaundice.\u00a0 People can die during this stage due to severe poisoning.<sup>1<\/sup><\/p>\n<p>Acetaminophen toxicity is diagnosed by measurement of the serum acetaminophen level using the Rumack-Matthew nomogram (see image below).\u00a0 The nomogram plots the initial concentration versus time of ingestion.\u00a0 In the study in which it was developed, a discriminatory line was originally drawn based on the observations of patients, separating those who developed hepatotoxicity from those who did not.\u00a0 Those who fall at or above the line should be treated for toxicity.<sup>2<\/sup><\/p>\n<p>The nomogram used in the United States uses a discriminatory line that was arbitrarily lowered by twenty five percent to increase sensitivity.\u00a0 It is called the \u201ctreatment line\u201d or the \u201c150-line,\u201d because it starts at a concentration of 150 \u03bcg\/mL at 4 hours after ingestion.\u00a0 Use of this line only has a one to three percent failure rate and it should be considered adequate and reliable in assessing acetaminophen toxicity when followed correctly. However, its weakness is that the time of ingestion must be known to make an assessment.<sup>2<\/sup>\u00a0 Some other issues concerning the nomogram are that it is not useful after chronic repeated overdose and that ingestion of sustained-release products or co-ingestion of anticholinergic, salicylate, or opioid products may cause delayed elevation of serum levels thereby making interpretation of the nomogram difficult.<sup>3<\/sup><\/p>\n<p>N-acetylcysteine is the accepted antidote for acetaminophen poisoning.\u00a0 It is indicated for all patients at significant risk for hepatotoxicity.\u00a0 This includes those who fall above the \u201ctreatment line\u201d on the Rumack-Matthew nomogram, patients with an unknown time of ingestion and a serum acetaminophen concentration &gt;10 mcg\/mL, and patients with a history of acetaminophen ingestion and any evidence of liver injury.\u00a0 Other possible treatments include the use of activated charcoal, which binds to acetaminophen in the stomach or intestines in order to keep the body from absorbing it and in severe cases, a liver transplant.<sup>1 <\/sup><\/p>\n<p>Image: Source: Acetaminophen, <i>Goldfrank&#8217;s Toxicologic Emergencies, 10e<\/i>Citation: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. <i>Goldfrank&#8217;s Toxicologic Emergencies, 10e<\/i>; 2015 Available at: <a href=\"http:\/\/accesspharmacy.mhmedical.com\/ViewLarge.aspx?figid=65093260&#038;gbosContainerID=0&#038;gbosid=0\" target=\"new\" class=\"external external_icon\">http:\/\/accesspharmacy.mhmedical.com\/ViewLarge.aspx?figid=65093260&amp;gbosContainerID=0&amp;gbosid=0<\/a> Accessed: February 26, 2018<\/p>\n<p><b>\u00a0<\/b><\/p>\n<p><b>\u00a0<\/b><\/p>\n<p><b>\u00a0<\/b><\/p>\n<p><b>SOURCES:<\/b><\/p>\n<ol>\n<li>Droxia\u00ae (Hydroxyurea) [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; Revised 03\/01\/2016.<\/li>\n<li>Chabner B, Barnes J, Neal J, et al. Targeted therapies: tyrosine kinase inhibitors, monoclonal antibodies, and cytokines. In: Brunton L, Chabner B, Knollman B, eds. Goodman &amp; Gilman&#8217;s The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill, 2011:1731-54.<\/li>\n<li>Rees D, Williams T, Gladwin M. Sickle-cell disease.\u00a0Lancet.\u00a02010;376(9757):2018-31.<\/li>\n<li>PL Detail-Document, Management of Sickle Cell Disease. Pharmacist\u2019s Letter\/Prescriber\u2019s Letter. <a href=\"https:\/\/pharmacist.therapeuticresearch.com\/Content\/Segments\/PRL\/2015\/Feb\/Management-of-Sickle-Cell-Disease-8101\" target=\"new\" class=\"external external_icon\">https:\/\/pharmacist.therapeuticresearch.com\/Content\/Segments\/PRL\/2015\/Feb\/Management-of-Sickle-Cell-Disease-8101.<\/a> Published 02\/01\/2015. Accessed 10\/20\/2017.<\/li>\n<li>National Heart, Lung, and Blood Institute. Evidence-based management of sickle cell disease: expert panel report 2014. <a href=\"https:\/\/www.nhlbi.nih.gov\/sites\/default\/files\/media\/docs\/sickle-cell-disease-report%20020816_0.pdf\" target=\"new\" class=\"external external_icon\">https:\/\/www.nhlbi.nih.gov\/sites\/default\/files\/media\/docs\/sickle-cell-disease-report%20020816_0.pdf.<\/a> Published 09\/012014. Accessed 10\/20\/2017.<\/li>\n<li>Hehlmann R, Heimpel H, Hasford J,\u00a0et al. Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group.\u00a0Blood.\u00a01994;84(12):4064-77.<\/li>\n<li>Cortes\u00a0J, Kantarjian H. How I treat newly diagnosed chronic phase CML. Blood. 2012;120(7):1390-7.<\/li>\n<li>Hochhaus A, Saussele S, Rosti G,\u00a0et al. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.\u00a0Ann Oncol.\u00a02017;28(suppl_4):iv41-51.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>By: Kathleen Horan, PharmD Candidate c\/o 2020 &#8211; During my institutional Introductory Pharmacy Practice Experiential (IPPE) rotation in the emergency department at NYU Winthrop University Hospital in the spring of 2018, I witnessed a variety of interesting cases while shadowing my preceptor, emergency department pharmacist Megan Czuba, PharmD. Among these emergencies cases, I witnessed a&hellip;<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7,4],"tags":[],"class_list":["post-3372","post","type-post","status-publish","format-standard","hentry","category-clinical","category-featured"],"views":891,"_links":{"self":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/3372","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/comments?post=3372"}],"version-history":[{"count":0,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/3372\/revisions"}],"wp:attachment":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/media?parent=3372"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/categories?post=3372"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/tags?post=3372"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}