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Acetaminophen (APAP)  Poroma Babu Ebey Soman  Simardeep Singh  Image from <http://www.straightdope.com/images/art/2000/000929.gif>
References  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Pertinent Abbreviations ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html>.
Cases  ,[object Object],[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.  Image from <http://blogs.babycenter.com/wp-content/uploads/2008/09/images_baby_medicine1.jpg>
Cases ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Moling, Oswald, Cairon, Elena, Rimenti, Giovanni, et al. “Case Report: Severe Hepatotoxicity After Therapeutic Doses of Acetaminophen.”  Clinical Therapeutics  28.5 (May 2006) : 755-760. Web. 6 Oct. 2010.
Characteristics of Acetaminophen  ,[object Object],[object Object],[object Object],[object Object],[object Object],Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
Acetaminophen’s Chemistry  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Acetaminophen: ChemID Plus Lite . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. http://chem.sis.nlm.nih.gov/chemidplus/ProxyServlet?objectHandle=Search&actionHandle=getAll3DMViewFiles&nextPage=jsp%2Fcommon%2FChemFull.jsp%3FcalledFrom%3Dlite&chemid=0000103902&formatType=_3D (both image and data)
Acetaminophen’s Pharmaceutical Classes  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
Mechanism of Action of Acetaminophen  ,[object Object],[object Object],[object Object],[object Object],[object Object],Lucas, Ruth, Warner, T.D., Vojnovic, I., and Mitchell, J.A. “Cellular Mechanism of Acetaminophen: Role of Cyclo-oxygenase.”  The FASEB Journal  18 (10 Feb. 2005). Web 6 Oct. 2010.
Acetaminophen Mechanism of Toxicity  ,[object Object],[object Object],[object Object],[object Object],[object Object],Moling, Oswald, Cairon, Elena, Rimenti, Giovanni, et al. “Case Report: Severe Hepatotoxicity After Therapeutic Doses of Acetaminophen.”  Clinical Therapeutics  28.5 (May 2006) : 755-760. Web. 6 Oct. 2010.
Acetaminophen Mechanism of Toxicity  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Moling, Oswald, Cairon, Elena, Rimenti, Giovanni, et al. “Case Report: Severe Hepatotoxicity After Therapeutic Doses of Acetaminophen.”  Clinical Therapeutics  28.5 (May 2006) : 755-760. Web. 6 Oct. 2010.
Acetaminophen Metabolism Source: &quot;Acetaminophen Metabolism.&quot;  Wikimedia Commons . Web. 8 Oct 2010. <http://upload.wikimedia.org/wikipedia/commons/1/12/Paracetamol_metabolism.svg
Acetaminophen’s Indication ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
Acetaminophen’s Indication ,[object Object],[object Object],[object Object],Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
Routes of Exposure  ,[object Object],[object Object],[object Object],[object Object],[object Object],Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1> Image taken from <http://www.clipartheaven.com/show/clipart/health_&_medical/cartoons/taking_medicine_2-gif.html>
Neonatal Case: Route of Administration  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Multiple Risk Case: Route of Administration  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Moling, Oswald, Cairon, Elena, Rimenti, Giovanni, et al. “Case Report: Severe Hepatotoxicity After Therapeutic Doses of Acetaminophen.”  Clinical Therapeutics  28.5 (May 2006) : 755-760. Web. 6 Oct. 2010.
Populations at Risk  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
Source:  WATSON, WILLIAM. &quot;2003 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System&quot;  AMERICAN JOURNAL OF EMERGENCY MEDICINE  22.5 (2004): 386. Web. 8 Oct 2010. <http://www.aapcc.org/dnn/Portals/0/AJEM%20-%20AAPCC%20Annual%20Report%202003.pdf>
Neonatal Case  ,[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.  Image from <http://blogs.babycenter.com/wp-content/uploads/2008/09/images_baby_medicine1.jpg>
Multiple Risk Case  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Moling, Oswald, Cairon, Elena, Rimenti, Giovanni, et al. “Case Report: Severe Hepatotoxicity After Therapeutic Doses of Acetaminophen.”  Clinical Therapeutics  28.5 (May 2006) : 755-760. Web. 6 Oct. 2010.
Biological Fate ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Acetaminophen (APAP) N-acetyl-p-benzo-quinone imine (NAPQI) Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
Biological Fate (Con’t) ,[object Object],[object Object],[object Object],[object Object],Excretion differences of Acetaminophen in Children vs. Adults Source:  Kociancic, Todd. &quot;http://www.medscape.com/viewarticle/459187_2.&quot;  Medscape Pharmacist . Pharmacotherapy Publications Inc, 2003. Web. 8 Oct 2010. <http://www.medscape.com/viewarticle/459187_2>.  Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
Children vs. Adults ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
General Effects of Toxicity ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
Effects Continued ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
Teratogenicity ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Source: &quot;Two-day old baby with a good case of jaundice.&quot;  Jaundice (Hyperbilirubinemia) . Web. 11 Oct 2010. <http://navelgazingmidwife.squarespace.com/storage/092smsm.jpg?__SQUARESPACE_CACHEVERSION=1270062632364>. A two day old baby with Jaundice Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
Toxicogenomics Biomarkers ,[object Object],[object Object],[object Object],[object Object],Sources:  Madadi, Parvaz, et al. &quot;Safety of codeine during breastfeeding.&quot;  Canadian Family Physician  53.1 (2007): 33-35. Web. 12 Oct 2010. <http://www.cfp.ca/cgi/content/full/53/1/33>.  Shuldiner, Alan, Joan Hebert, and Michelle Carillo. &quot;Annotated PGx Gene Information for CYP3A4.&quot;  PharmGKB . Stanford University , July 2007. Web. 12 Oct 2010. <http://www.pharmgkb.org/search/annotatedGene/cyp3a4/>.  Ueshima, Y, et al. &quot;Acetaminophen metabolism in patients with different cytochrome P-4502E1 genotypes.&quot;  Alcoholism: Clinical and Experimental Research  20.1 (1996): 25A-28A. Web. 12 Oct 2010. <http://www.ncbi.nlm.nih.gov/pubmed/8659683>.
CYP 2E1 Role in Toxicity Source:  &quot;Determination of APAP-induced liver and kidney injury in wild-type and Cyp2e1-null mice.&quot; I dentification of Novel Toxicity-associated Metabolites by Metabolomics and Mass Isotopomer Analysis of Acetaminophen Metabolism in Wild-type and Cyp2e1-null Mice . Web. 12 Oct 2010. <http://www.jbc.org/content/283/8/4543/F1.large.jpg>.
Secondary Effects ,[object Object],[object Object],[object Object],[object Object],[object Object],Source: Imaeda, Avlin, Watanabe, Azuma, et al. &quot;Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome.&quot;  Journal of Clinical Investigation  119.2 (2009): 305-315. Web. 11 Oct 2010. <http://www.jci.org/articles/view/35958>.
Tlr9 and Nalp3 Pathways Source: Imaeda, Avlin, Watanabe, Azuma, et al. &quot;Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome.&quot;  Journal of Clinical Investigation  119.2 (2009): 305-315. Web. 11 Oct 2010. <http://www.jci.org/articles/view/35958>.
Exposure Risk Assessment •  How much? •  What preparation? •  When? •  Pattern of Abuse? •  Intent? •  Comorbid or Drug use? Helps determine patient risk factors, a time frame for when the drug was ingested, how much was ingested and enable the health care worker to arrive at a proper diagnosis and treatment Acetaminophen: Toxicology Data Network (TOXNET) . National   Library   of   Medicine  : Hazardous   Substances   Data   Bank (HSDA),  1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
Symptoms ,[object Object],[object Object],[object Object],O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html>. Image taken from http://4.bp.blogspot.com/_EQiYy5Raips/TEWsm9LlYPI/AAAAAAAAAcA/KmfU6fMU0N4/s1600/sick_girl.jpg 08 Oct. 2010
Stage 1 ,[object Object],[object Object],[object Object],O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html>. Image taken from http://3.bp.blogspot.com/_w5baxtfyh30/THFIB3T8qvI/AAAAAAAAAZg/sdhqVxj4h60/s1600/nausea.gif.  08 Oct. 2010
Stage 2 ,[object Object],[object Object],[object Object],O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html>. Image taken from http://anatomy.med.umich.edu/surface/abdomen/ab_quadrant.jpeg.  08 Oct. 2010
Stage 3 ,[object Object],[object Object],[object Object],[object Object],O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html>. Image 1 taken from http://www.merlehamburger.net/images/pancreas2.jpg. 08 Oct. 2010. Image 2 taken from http://www.osovo.com/diagram/diagram-of-kidney.gif. 08 Oct. 2010.
Stage 4 ,[object Object],[object Object],[object Object],[object Object],O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html>. Image taken from http://www.knowyourgut.com/wp-content/uploads/2009/07/emergency-room.jpg.  08 Oct. 2010
Other Consequences of Severe Toxicity ,[object Object],[object Object],[object Object],[object Object],O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html>.
Serum Acetaminophen Levels ,[object Object],[object Object],[object Object],[object Object],Rumack-Matthew nomogram O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html>.
Neonatal Case  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Multiple Risk Case  ,[object Object],[object Object],[object Object],Moling, Oswald, Cairon, Elena, Rimenti, Giovanni, et al. “Case Report: Severe Hepatotoxicity After Therapeutic Doses of Acetaminophen.”  Clinical Therapeutics  28.5 (May 2006) : 755-760. Web. 6 Oct. 2010.
Patient Assessment (Labs) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Lab Values O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html >. Schaefer, Jeffrey P. &quot;Acetaminophen Intoxication.&quot; Dr. Jeffrey P Schaefer, 14 Oct. 2007. Web. 10 Oct. 2010.  <http://dr.schaeferville.com/presentations/20071014_acetaminophen_intoxication.pdf>. Measure Indicative of Toxicity Serum Creatinine (SrCr) Elevated over 3.4 mg/dL Creatinine Clearance (CrCl) Lowered International Normalized Ratio (INR) Elevated Prothrombin Time (PT) Elevated over 100 seconds Aspartate Aminotransferase (AST) Elevated Alanine Transaminase (ALT) Elevated Billirubin Elevated over 18 mg/dL
Treatment ,[object Object],[object Object],[object Object],[object Object],[object Object],Schaefer, Jeffrey P. &quot;Acetaminophen Intoxication.&quot; Dr. Jeffrey P Schaefer, 14 Oct. 2007. Web. 10 Oct. 2010.  <http://dr.schaeferville.com/presentations/20071014_acetaminophen_intoxication.pdf>. O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html>. Image 1 taken from http://wellnessmama.files.wordpress.com/2009/11/221834-main_full.jpg. 10 Oct. 2010 Image 2 taken from https://www.lifeluxure.com/images/N-Acetyl-Cysteine.jpg.  10 Oct. 2010
Activated Charcoal ,[object Object],[object Object],Schaefer, Jeffrey P. &quot;Acetaminophen Intoxication.&quot; Dr. Jeffrey P Schaefer, 14 Oct. 2007. Web. 10 Oct. 2010.  <http://dr.schaeferville.com/presentations/20071014_acetaminophen_intoxication.pdf>. DRUGDEX® System . Thomson Reuters (Healthcare) Inc. http://www.thomsonhc.com.  10 Oct. 2010 Image 1 taken from http://www.nynaturalhealthcenter.com/vitamins/images/activatedcharcoal1.jpg. 10 Oct. 2010 Given at 1-2 grams per Kilogram Body Weight
N-Acetylcysteine  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],&quot;Focus On: Acetaminophen Toxicity and Treatment.&quot;  American College of Emergency Physicians . Web. 08 Oct. 2010.  <http://www.acep.org/publications.aspx?id=26830>. O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html>. Image 1 taken from http://www.kingguide.com/images/vials.gif. 08 Oct. 2010.
Lab Values in the Neonatal Case  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Lab Values in Neonatal Case ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Lab Values in Neonatal Case ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Neonatal Case: Treatment  ,[object Object],[object Object],[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Neonatal Case: Progress ,[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Neonatal Case: Treatment (con’t) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Neonatal Case: Treatment(con’t)  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Lab Values in Neonatal Case: After Treatment  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Neonatal Case: After Treatment  ,[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Lab Values in Multiple Risk Case ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Moling, Oswald, Cairon, Elena, Rimenti, Giovanni, et al. “Case Report: Severe Hepatotoxicity After Therapeutic Doses of Acetaminophen.”  Clinical Therapeutics  28.5 (May 2006) : 755-760. Web. 6 Oct. 2010.
Multiple Risk Case: Treatment  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Moling, Oswald, Cairon, Elena, Rimenti, Giovanni, et al. “Case Report: Severe Hepatotoxicity After Therapeutic Doses of Acetaminophen.”  Clinical Therapeutics  28.5 (May 2006) : 755-760. Web. 6 Oct. 2010.
Multiple Risk Case: After Treatment  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Moling, Oswald, Cairon, Elena, Rimenti, Giovanni, et al. “Case Report: Severe Hepatotoxicity After Therapeutic Doses of Acetaminophen.”  Clinical Therapeutics  28.5 (May 2006) : 755-760. Web. 6 Oct. 2010.
Comparison of Routes of Administration &quot;Focus On: Acetaminophen Toxicity and Treatment.&quot;  American College of Emergency Physicians . Web. 08 Oct. 2010.  <http://www.acep.org/publications.aspx?id=26830>. O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot;  Merck & Co., Inc.  Merck & Co. Web. 08 Oct. 2010.  http://www.merck.com/mmpe/sec21/ch326/ch326c.html>. &quot;Clinical Policy: Critical Issues in the Management of Patients Presenting to the Emergency Department with Acetaminophen Overdose.&quot;  National Guideline C Clearinghouse . US Department of Health and Human Services, 15 Feb. 2008. Web. 10 Oct. 2010.  <http://www.guideline.gov/content.aspx?id=11428&search=acetaminophen+overdose>. Oral (PO) Intravenous (IV) Low Cost High Cost Long duration of therapy (72 hours) Shorter duration of therapy (20 hours) Adverse Effects are minimal  Usually Nausea and Emesis More Adverse Effects AnaphylactOID Reaction (No IgE action) Vomiting <1hr post-administration requires the dose to be readministered Adverse effects more common in asthmatic patients Poor palatability Rash, Itching, Bronchospasm, Tachycardia, Hypotension Patients that are not candidates for oral route have to use IV Symptoms are usually mild  (severe in ~1% of cases) Ex. Neonates, Patients with altered mental status, GI bleed, repeat vomiting etc. Hold infusion and re-challenge with lower dose (Low recurrence rate)
Article Title: Incidence of adverse drug reactions induced by N-acetylcysteine in    patients with acetaminophen overdose. ,[object Object],Human & Experimental Toxicology, Mar2010, Vol. 29 Issue 3, p153-160, 8p, 1 Diagram, 3 Charts, 1 Graph Diagram; found on p155
Article Title: Incidence of adverse drug reactions induced by N-acetylcysteine in patients with    acetaminophen overdose. ,[object Object],Human & Experimental Toxicology, Mar2010, Vol. 29 Issue 3, p153-160, 8p, 1 Diagram, 3 Charts, 1 Graph Graph; found on p157
Patient Education ,[object Object],[object Object],[object Object],[object Object],[object Object],DRUGDEX® System . Thomson Reuters (Healthcare) Inc. http://www.thomsonhc.com.  10 Oct. 2010 Image 1 taken from http://blog.oregonlive.com/health_impact/2009/07/acetaminophen.JPG. 10 Oct. 2010
Neonatal Case: What Went WRONG  ,[object Object],[object Object],[object Object],[object Object],[object Object],Walls, L, CF Baker, and S Sarkar. “Perinatal/Neonatal Case Presentation: Acetaminophen-induced Hepatic Failure with Encephalopathy in a Newborn .” Journal of  Perinatology  27.2 (Feb. 2007): 133-136. Web. 6 Oct. 2010.
Acetaminophen Containing Products ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],These are only the commonly used products.  There are many other products available. &quot;Acetaminophen (APAP) & Liver Damage.&quot;  TYLENOL® - The Official Website for All TYLENOL® Products . McNeil INC. Web. 08 Oct. 2010.  <http://www.tylenol.com/page.jhtml?id=tylenol/news/acetaminophen_liver_damage.inc>.
Summary ,[object Object],[object Object],[object Object],[object Object],[object Object]
Summary Video Source:  &quot;Toxicity of Acetaminophen and Salicylates - USMLE Study Songs.&quot;  YouTube Channel - StudyWithSubstanceP . Web. 12 Oct 2010. <http://www.youtube.com/watch?v=NepKOh5JrfE>.

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Acetaminophen (APAP) Toxicity: Clinical Cases, Diagnosis, Pathology, Treatments and Patient Education

  • 1. Acetaminophen (APAP) Poroma Babu Ebey Soman Simardeep Singh Image from <http://www.straightdope.com/images/art/2000/000929.gif>
  • 2.
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  • 12. Acetaminophen Metabolism Source: &quot;Acetaminophen Metabolism.&quot; Wikimedia Commons . Web. 8 Oct 2010. <http://upload.wikimedia.org/wikipedia/commons/1/12/Paracetamol_metabolism.svg
  • 13.
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  • 19. Source: WATSON, WILLIAM. &quot;2003 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System&quot; AMERICAN JOURNAL OF EMERGENCY MEDICINE 22.5 (2004): 386. Web. 8 Oct 2010. <http://www.aapcc.org/dnn/Portals/0/AJEM%20-%20AAPCC%20Annual%20Report%202003.pdf>
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  • 29. CYP 2E1 Role in Toxicity Source: &quot;Determination of APAP-induced liver and kidney injury in wild-type and Cyp2e1-null mice.&quot; I dentification of Novel Toxicity-associated Metabolites by Metabolomics and Mass Isotopomer Analysis of Acetaminophen Metabolism in Wild-type and Cyp2e1-null Mice . Web. 12 Oct 2010. <http://www.jbc.org/content/283/8/4543/F1.large.jpg>.
  • 30.
  • 31. Tlr9 and Nalp3 Pathways Source: Imaeda, Avlin, Watanabe, Azuma, et al. &quot;Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome.&quot; Journal of Clinical Investigation 119.2 (2009): 305-315. Web. 11 Oct 2010. <http://www.jci.org/articles/view/35958>.
  • 32. Exposure Risk Assessment • How much? • What preparation? • When? • Pattern of Abuse? • Intent? • Comorbid or Drug use? Helps determine patient risk factors, a time frame for when the drug was ingested, how much was ingested and enable the health care worker to arrive at a proper diagnosis and treatment Acetaminophen: Toxicology Data Network (TOXNET) . National Library of Medicine : Hazardous Substances Data Bank (HSDA), 1 Apr. 1983. Web. 8 Oct. 2010. <http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~ZSagYF:1>
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  • 43. Lab Values O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot; Merck & Co., Inc. Merck & Co. Web. 08 Oct. 2010. http://www.merck.com/mmpe/sec21/ch326/ch326c.html >. Schaefer, Jeffrey P. &quot;Acetaminophen Intoxication.&quot; Dr. Jeffrey P Schaefer, 14 Oct. 2007. Web. 10 Oct. 2010. <http://dr.schaeferville.com/presentations/20071014_acetaminophen_intoxication.pdf>. Measure Indicative of Toxicity Serum Creatinine (SrCr) Elevated over 3.4 mg/dL Creatinine Clearance (CrCl) Lowered International Normalized Ratio (INR) Elevated Prothrombin Time (PT) Elevated over 100 seconds Aspartate Aminotransferase (AST) Elevated Alanine Transaminase (ALT) Elevated Billirubin Elevated over 18 mg/dL
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  • 59. Comparison of Routes of Administration &quot;Focus On: Acetaminophen Toxicity and Treatment.&quot; American College of Emergency Physicians . Web. 08 Oct. 2010. <http://www.acep.org/publications.aspx?id=26830>. O'Malley, Gerald F. &quot;Acetaminophen Poisoning: Poisoning: Merck Manual Professional.&quot; Merck & Co., Inc. Merck & Co. Web. 08 Oct. 2010. http://www.merck.com/mmpe/sec21/ch326/ch326c.html>. &quot;Clinical Policy: Critical Issues in the Management of Patients Presenting to the Emergency Department with Acetaminophen Overdose.&quot; National Guideline C Clearinghouse . US Department of Health and Human Services, 15 Feb. 2008. Web. 10 Oct. 2010. <http://www.guideline.gov/content.aspx?id=11428&search=acetaminophen+overdose>. Oral (PO) Intravenous (IV) Low Cost High Cost Long duration of therapy (72 hours) Shorter duration of therapy (20 hours) Adverse Effects are minimal Usually Nausea and Emesis More Adverse Effects AnaphylactOID Reaction (No IgE action) Vomiting <1hr post-administration requires the dose to be readministered Adverse effects more common in asthmatic patients Poor palatability Rash, Itching, Bronchospasm, Tachycardia, Hypotension Patients that are not candidates for oral route have to use IV Symptoms are usually mild (severe in ~1% of cases) Ex. Neonates, Patients with altered mental status, GI bleed, repeat vomiting etc. Hold infusion and re-challenge with lower dose (Low recurrence rate)
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  • 66. Summary Video Source: &quot;Toxicity of Acetaminophen and Salicylates - USMLE Study Songs.&quot;  YouTube Channel - StudyWithSubstanceP . Web. 12 Oct 2010. <http://www.youtube.com/watch?v=NepKOh5JrfE>.

Editor's Notes

  1. Episodic emesis simply refers to vomiting periodically.
  2. Point out pka to show that it can irritate the stomach and it can be enteric coated
  3. PGE2 are mediators of fever, pain, and inflammation
  4. Basically there really is not any major ways that the general population may be exposed to APAP other then ingesting it. We have to remember that this is a drug and it usually comes in oral form. What causes it to be so significant is the rate of exposure that is seen in the general population. Since as we said before it is something that is a common OTC drug, most household do have it in their homes at all time.
  5. As Ebey said earlier, children are at a higher risk then others to get APAP toxicity and this is going to be clearly demonstrated in our Neonatal case.
  6. CPK – Creatine Phospho Kinase levels
  7. Basically what we see are the classical GI irritation but no major notable signs
  8. Tenderness and abdominal pain, enlarged liver
  9. Jaundice, GI bleeding, edemas, multi organ failures
  10. No apparently physical symptoms but heavy liver damage or coma or death. - Stage 4 patients have hepatic histological changes such as increased CYP2E1 enzymes which may last for up to 3 months
  11. Rumack-Matthew nomogram is …
  12. Now the lab values are really according to who the patient is and this will be further explained and explored as we talk about the individual cases.
  13. NR = normal range
  14. These were all given because he was initially diagnosed with sepsis with renal failure, liver failure, and coagulopathy. The initial treatment corrected his hypoglycemia, dehydration, and electrolyte imbalance, but did not help with his persistent encephalopathy.
  15. Just as a side note: I am sure many of u have heard or even watched the tv show “House MD” and kn that he was addicted to Vicodin. Vicodin of course is a narcotic analgesic that is a combination of hydrocodone and paracetamol. While something like Vicodin is much more addicting, acetaminophen alone can be just as addicting. Its just that using acetaminophen to alleviate pain has become so common that many people underestimate it.