Author(s):
Ulfa Kholili, Yahya Haryo Nugroho, Titong Sugihartono, Iswan A. Nusi, Poernomo Boedi Setiawan
Email(s):
ulfakholili1975@gmail.com
DOI:
10.52711/0974-360X.2023.00329
Address:
Ulfa Kholili1*, Yahya Haryo Nugroho2, Titong Sugihartono1, Iswan A. Nusi1, Poernomo Boedi Setiawan1
1Gastroenterology-Hepatology Division, Department of Internal Medicine, Faculty of Medicine - Dr. Soetomo General Academic Hospital, Universitas Airlangga, Surabaya, 60131, Indonesia.
2Department of Internal Medicine, Faculty of Medicine - Dr. Soetomo General Academic Hospital, Universitas Airlangga, Surabaya, 60131, Indonesia.
*Corresponding Author
Published In:
Volume - 16,
Issue - 4,
Year - 2023
ABSTRACT:
The most widely prescribed pain and fever reliever in both the United States and Europe is acetaminophen, also referred to as paracetamol. It is included on the World Health Organization's List of Essential Medications, which includes the best and safest medications required in a healthcare system. Although acetaminophen overdose has been related to fatal and nonfatal hepatic necrosis since 1966, it is generally safe when used at standard therapeutic levels (up to 4000 mg per 24 hours). It involves fundamental metabolic pathways that actually occur on microsomes in hepatocytes, and overdosing on acetaminophen causes liver damage followed by liver failure. The typical acetaminophen overdose remedy is N-acetylcysteine (NAC), which is administered to all patients at high risk of liver toxicity. The standard of therapy is NAC medication, although for some people, liver transplantation may be a life-saving procedure. We shall explore the safety of acetaminophen in associated with liver injury in this review article, particularly in terms of epidemiology, pharmacokinetic, hepatotoxicity, clinical presentation, and the treatment.
Cite this article:
Ulfa Kholili, Yahya Haryo Nugroho, Titong Sugihartono, Iswan A. Nusi, Poernomo Boedi Setiawan. Liver injury associated with Acetaminophen: A Review. Research Journal of Pharmacy and Technology 2023; 16(4):2006-2. doi: 10.52711/0974-360X.2023.00329
Cite(Electronic):
Ulfa Kholili, Yahya Haryo Nugroho, Titong Sugihartono, Iswan A. Nusi, Poernomo Boedi Setiawan. Liver injury associated with Acetaminophen: A Review. Research Journal of Pharmacy and Technology 2023; 16(4):2006-2. doi: 10.52711/0974-360X.2023.00329 Available on: https://rjptonline.org/AbstractView.aspx?PID=2023-16-4-78
REFERENCES:
1. World of Molecules. Chemical and Physical Properties of Tylenol Molecule-Acetaminophen [Internet]. The Acetaminophen Molecule-Tylenol. 2008 [cited 2021 May 20]. Available from: https://www.worldofmolecules.com/drugs/tylenol.htm
2. Brune K. Renner B. Tiegs G. Acetaminophen/paracetamol: A history of errors, failures and false decisions. Eur J Pain. 2015 Aug;19(7):953–65.doi:10.1002/ejp.621.
3. Salhanick SD. Acetaminophen. In: Aghababian R V, editor. Essentials of emergency medicine. 2nd ed. Canada: Jones & Bartlett Publishers; 2010:814–6.
4. Hassan NAGM. Gacem SA. Al-Qaysi AA-H. AlAani MJ. Prevalence of pain and self-medication pattern of Paracetamol and NSAIDs among university students in United Arab Emirates. Research Journal of Pharmacy and Technology. 2021;3393–8. doi:10.52711/0974-360X.2021.00590
5. Singh RJ. Kohli K. Self-Medication Practices among MBBS students in North Indian Medical College. Research Journal of Pharmacy and Technology. 2021 Jan 5;2653–8. doi:10.52711/0974-360X.2021.00468.
6. World Health Organization. WHO Model Lists of Essential Medicines [Internet]. 21st ed. apps.who.int. Geneva; 2019 [cited 2021 May 30]. Available from: https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-MVP-EMP-IAU-2019.06-eng.pdf
7. Physicians Desk Reference Inc. Physicians’ desk reference. 70th ed. United States: PDR Network, LLC; 2015.
8. Davidson DGD. Eastham WN. Acute Liver Necrosis Following Overdose of Paracetamol. British Medical Journal. 1966;2(5512):497–9.doi:10.1136/bmj.2.5512.497
9. Seeff LB. Cuccherini BA. Zimmerman HJ. Adler E. Benjamin SB. Acetaminophen hepatotoxicity in alcoholics: a therapeutic misadventure. Annals of Internal Medicine. 1986 Mar 1;104(3):399–404.doi: 10.7326/0003-4819-104-3-399.
10. Bonkovsky HL. Acetaminophen Hepatotoxicity, Fasting, and Ethanol. JAMA. 1995;274(4):301.
11. Whitcomb DC. Block GD. Association of Acetaminophen Hepatotoxicity With Fasting and Ethanol Use. JAMA. 1994 Dec 21;272(23):1845–50.doi: 10.1001/jama.1994.03520230055038.
12. Bunchorntavakul C. Reddy KR. Acetaminophen-related Hepatotoxicity. Clinical Liver Disease. 2013;17(4):587–607.doi: 10.1016/j.cld.2013.07.005
13. Yoon E. Babar A. Choudhary M. Kutner M. Pyrsopoulos N. Acetaminophen-induced hepatotoxicity: A comprehensive update. J Clin Transl Hepatol. 2016;4(2):131–142.doi:10.14218/JCTH.2015.00052.
14. Watson WA. Litovitz TL. Rodgers GC. Klein-Schwartz W. Reid N. Youniss J. et al. 2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. American Journal of Emergency Medicine. 2005;23(5):589–666.doi: 10.1016/j.ajem.2005.05.001
15. Ostapowicz G. Fontana RJ. Schioødt FV. Larson A. Davern TJ. Han SHB. et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Annals of Internal Medicine. 2002;137(12):947–54.doi: 10.7326/0003-4819-137-12-200212170-00007.
16. Blieden M. Paramore LC. Shah D. Ben-Joseph R. A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States. Expert Review of Clinical Pharmacology. 2014;7(3):341–8.doi: 10.1586/17512433.2014.904744.
17. Larson AM. Polson J. Fontana RJ. Davern TJ. Lalani E. Hynan LS. et al. Acetaminophen‐induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42(6):1364–72.doi: 10.1002/hep.20948.
18. Marzilawati AR. Ngau YY. Mahadeva S. Low rates of hepatotoxicity among Asian patients with paracetamol overdose: a review of 1024 cases. BMC Pharmacology Toxicology. 2012;13:8.doi: 10.1186/2050-6511-13-8.
19. Wisher D. Martindale: The Complete Drug Reference. 37th ed. Journal of Medical Library Association. 2012;100(1):75–6.doi:10.3163/1536-5050.100.1.018.
20. Buckingham R. Martindale: The Complete Drug Reference. 40th ed. Pharmaceutical Press:2020.
21. Premakumari KB. Mahesh AR. Murugan V. Ezhilarasan V. Simultaneous Estimation of Paracetamol and Zaltoprofen in Pharmaceutical Dosage Form by HPTLC. Research Journal of Pharmacy and Technology. 2019;12(5):2075.doi:10.5958/0974-360X.2019.00343.3.
22. Zainuddin HZM. Zainuddin LRM. Paracetamol Induced Liver Morphological Changes after Acute Dosing. Research Journal of Pharmacy and Technology. 2015 Jan 5;8(4):382.doi:10.5958/0974-360X.2015.00064.5.
23. Burns MJ. Friedman SL. Larson AM. Acetaminophen (paracetamol) Poisoning in Adults: Pathophysiology, Presentation, and Evaluation [Internet]. UpToDate. 2016 [cited 2021 May 28]:1–20. Available from: https://www.uptodate.com/contents/acetaminophen-paracetamol-poisoning-in-adults-pathophysiology-presentation-and-evaluation
24. Toff W. Paracetamol overdosage. British Medical Journal. 1978;1(6110):442.
25. Popiolek I. Hydzik P. Jagielski P. Zrodlowska M. Mystek K. Porebski G. Risk Factors for Hepatotoxicity Due to Paracetamol Overdose In Adults. Medical. 2021;57(8):1–9.doi: 10.3390/medicina57080752.
26. Caparrotta TM. Antoine DJ. Dear JW. Are Some People at Increased Risk of Paracetamol-Induced Liver Injury? A Critical Review of The Literature. European Journal of Clinical Pharmacolology. 2018;74(2):147–60.doi:10.1007/s00228-017-2356-6
27. Rathore P. Prakash RS. Roy A. Satapathy T. Singh V. Jain P. Hepatoprotective activity of isolated herbal compounds. Research Journal of Pharmacy and Technology.2014;7(2):229–34.
28. Leise MD. Poterucha JJ. Talwalkar JA. Drug-induced liver injury. Mayo Clinic Proceeding. 2014;89(1):95–106.
29. Fisher K. Vuppalanchi R. Saxena R. Drug-induced liver injury. Archive of Pathology Laboratory and Medicine. 2015;139(7):876–87.doi:10.5858/arpa.2014-0214-RA.
30. Lancaster EM. Hiatt JR. Zarrinpar A. Acetaminophen Hepatotoxicity: An Updated Review. Archive of Toxicology. 2015;89(2):193–9.doi:10.1007/s00204-014-1432-2
31. Suma MS. Jamuna KS. Ramesh CK. Mahmood R. Expression of Drug-Metabolizing Genes and Acetaminophen Drug Toxicity Studies on 3D Scaffold Culture of Huh-7 Cell Line. Research Journal of Pharmacy Technology.2020;13(5):2399.doi:10.5958/0974-360X.2020.00431.X
32. Jaeschke H. Williams CD. Ramachandran A. Bajt ML. Acetaminophen Hepatotoxicity and Repair: The Role of Sterile Inflammation and Innate Immunity. Liver International. 2012;32(1):8–20.doi: 10.1111/j.1478-3231.2011.02501.x
33. Ishitsuka Y. Kondo Y, Kadowaki D. Toxicological property of acetaminophen: the dark side of a safe antipyretic/analgesic drug? Biol Pharm Bull. 2020;43(2):195–206.
34. Dixon MF. Nimmo J. Prescott LF. Experimental paracetamol‐induced hepatic necrosis: A histopathological study. The Journal of Pathology. 1971;103(4):225–9.doi: 10.1002/path.1711030404.
35. McCaul TF. Fagan EA. Tovey G. Portmann B. Williams R. Zuckerman AJ. Fulminant hepatitis: An ultrastructural study. Journal of Hepatology. 1986;2(2):276–90.doi:10.1016/S0168-8278(86)80087-3
36. Manov I. Motanis H. Frumin I. Ciancu T. Hepatotoxicity of anti-inflammatory and analgesic drugs: Ultrastructural aspects. Acta Pharmacologica Sinica. 2006;27(3):259–72.doi: 10.1111/j.1745-7254.2006.00278.x
37. Placke ME. Ginsberg GL. Wyand DS. Cohen SD. Ultrastructural Changes during Acute Acetaminophen-Induced Hepatotoxicity in the Mouse: A Time and Dose Study. Toxicologic Pathology. 1987;15(4):431–8.doi: 10.1177/019262338701500407
38. Zein JG. Wallace DJ. Kinasewitz G. Toubia N. Kakoulas C. Early Anion Gap Metabolic Acidosis in Acetaminophen Overdose. American Journal of Emergency Medical. 2010;28(7):798–802.doi: 10.1016/j.ajem.2009.04.005
39. Islam G. Gahlot K. Mani M. Kumar P. Shukla D. Hepatoprotective Activity of Leucas cephalotes against Paracetamol induced Hepatotoxicity in Rats. Research Journal of Pharmacy and Technology. 2020 Jan 5;13(3):1183.doi:10.5958/0974-360X.2020.00218.8.
40. Yuvaraja KR. Santhiagu A. Jasemine S. Kumar KG. Hepatoprotective Activity of Chloroform and Ethyl Acetate Extract of Dipteracanthus patulus Against Paracetamol Induced Hepatotoxicity in Rats Through Antioxidant Mechanism. Research Journal of Pharmacy and Technology.2020;13(1):203.doi:10.5958/0974-360X.2020.00041.4.
41. Heard K. Dart R. Acetaminophen (paracetamol) poisoning in adults: treatment [Internet]. UpToDate. 2016 [cited 2021 May 29]:1–14. Available from: https://www.uptodate.com/contents/acetaminophen-paracetamol-poisoning-in-adults-treatment
42. Kirschner RI. Rozier CM. Smith LM. Jacobitz KL. Nomogram line crossing after acetaminophen combination product overdose. Journal of Toxicology. Clin Toxicolology (Phila). 2016;54(1):40–6. doi: 10.3109/15563650.2015.1110591
43. Ibadi MH. AL-Rekabi SHA. Abadi HA. A Study of The Effect of Octreotide and N-acetylcysteine on Inflammatory and Prognostic Parameters in Severe Acute Pancreatitis in Rats. Research Journal of Pharmacy and Technology. 2018;11(12):5461.doi:10.5958/0974-360X.2018.00996.4.
44. Wolf SJ. Heard K. Sloan EP. Jagoda AS. Clinical Policy: Critical Issues in the Management of Patients Presenting to the Emergency Department with Acetaminophen Overdose. Journal of Emergency Nursing. 2008;34(2):1–18. doi: 10.1016/j.annemergmed.2007.06.014.
45. Spiller HA. Winter ML. Klein-Schwartz W. Bangh SA. Efficacy of Activated Charcoal Administered More Than Four Hours after Acetaminophen Overdose. The Journal of Emergency Medicine. 2006;30(1):1–5.doi: 10.1016/j.jemermed.2005.02.019.
46. Hodgman MJ. Garrard AR. A review of acetaminophen poisoning. Critical Care Clinis. 2012;28(4):499–516.doi: 10.1016/j.ccc.2012.07.006.
47. Algren DA. Review of n-acetylcysteine for the treatment of acetaminophen (paracetamol) toxicity in pediatrics [Internet]. WHO.int. Geneva; 2008 [cited 2021 Mar 20]:1–18. Available from: https://www.who.int/selection_medicines/committees/subcommittee/2/acetylcysteine_rev.pdf
48. Heard KJ. Acetylcysteine for Acetaminophen Poisoning. The New England Journal of Medicine. 2008;359(3):285–92.doi:10.1056/NEJMct0708278.
49. Shetty R. Udupa N. Mutalik S. Kulkarni V. Rao V. Mechanisms and Therapeutics of N-acetylcysteine: A Recent Update. Research Journal of Pharmacy and Technology. 2019;12(5):2584.doi:10.5958/0974-360X.2019.00434.7.
50. Ershad M. Naji A. Vearrier D. N Acetylcysteine [Internet]. StatPearls. StatPearls Publishing, Treasure Island (FL); 2021 [cited 2021 Mar 28]. Available from: http://europepmc.org/abstract/MED/30725868
51. Daly FFS. O’Malley GF. Heard K. Bogdan GM. Dart RC. Prospective Evaluation of Repeated Supratherapeutic Acetaminophen (Paracetamol) Ingestion. Annals of Emergency Medicine. 2004;44(4):393–8. doi: 10.1016/j.annemergmed.2004.05.005.