19. Source: WATSON, WILLIAM. "2003 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System" 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: "Determination of APAP-induced liver and kidney injury in wild-type and Cyp2e1-null mice." 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>.
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31. Tlr9 and Nalp3 Pathways Source: Imaeda, Avlin, Watanabe, Azuma, et al. "Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome." 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. "Acetaminophen Poisoning: Poisoning: Merck Manual Professional." Merck & Co., Inc. Merck & Co. Web. 08 Oct. 2010. http://www.merck.com/mmpe/sec21/ch326/ch326c.html >. Schaefer, Jeffrey P. "Acetaminophen Intoxication." 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 "Focus On: Acetaminophen Toxicity and Treatment." American College of Emergency Physicians . Web. 08 Oct. 2010. <http://www.acep.org/publications.aspx?id=26830>. O'Malley, Gerald F. "Acetaminophen Poisoning: Poisoning: Merck Manual Professional." Merck & Co., Inc. Merck & Co. Web. 08 Oct. 2010. http://www.merck.com/mmpe/sec21/ch326/ch326c.html>. "Clinical Policy: Critical Issues in the Management of Patients Presenting to the Emergency Department with Acetaminophen Overdose." 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: "Toxicity of Acetaminophen and Salicylates - USMLE Study Songs." YouTube Channel - StudyWithSubstanceP . Web. 12 Oct 2010. <http://www.youtube.com/watch?v=NepKOh5JrfE>.
Notes de l'éditeur
Episodic emesis simply refers to vomiting periodically.
Point out pka to show that it can irritate the stomach and it can be enteric coated
PGE2 are mediators of fever, pain, and inflammation
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.
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.
CPK – Creatine Phospho Kinase levels
Basically what we see are the classical GI irritation but no major notable signs
Tenderness and abdominal pain, enlarged liver
Jaundice, GI bleeding, edemas, multi organ failures
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
Rumack-Matthew nomogram is …
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.
NR = normal range
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.
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.
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