Paracetamol poisoning
Paracetamol poisoning happens when someone takes too much paracetamol[1] ‒ a common drug for relieving pain ‒ within a short time.[2] The poisoning tends to happen in three phases.[3]
Phases
[change | change source]First phase
[change | change source]The first phase begins within hours of someone overdosing on paracetamol.[4][5] Symptoms include nausea, vomiting, sweating, and a pale look,[4][5] though some patients do not show symptoms.[4][5]
Second phase
[change | change source]The second phase occurs within 24 and 72 hours of the overdose when liver damage happens.[4][5] The damage is typically found in liver cells that metabolize the paracetamol.[4][5]
Liver biopsy tends to show coagulative necrosis in zone 3 of the liver acinus, around the central venules, as these hepatocytes have higher concentrations of cytochrome P450 enzymes compared to zone 1 hepatocytes around the acinus' portal venule.[6]
The liver damage is often not noticed until right upper quadrant abdominal pain occurs,[7] while the international normalized ratio (INR) and the liver transaminases ALT and AST rise to abnormal levels.[7][8]
Pathophysiology
[change | change source]This can happen when the sulfate and glucuronide pathways, and the cytochrome P450 enzyme system, are saturated with toxic reactive intermediates from the metabolized paracetamol ‒ especially N-acetyl-p-benzoquinone imine (NAPQI).[9]
The lack of glutathione to detoxify the excess NAPQI allows it to damage liver cells massively,[9] causing liver failure.[9] Acute kidney failure may also occur due to either hepatorenal syndrome or multiple organ dysfunction syndrome.[8][9]
Third phase
[change | change source]The third phase follows at 3 to 5 days, marked by massive liver cell deaths and fulminant liver failure,[3] along with sepsis, brain swelling, kidney failure, and multiple organ failure that cause death.[3]
Treatment
[change | change source]
Paracetamol poisoning can be treated by activated[10] charcoal.[11] The antidote acetylcysteine is sometimes given.[11] A liver transplant may be required if the liver damage is huge.[11] Liver failure is rare when early treatment is given.[11] Death occurs in 0.1% of the treated cases.[11]
Related pages
[change | change source]References
[change | change source]- ↑ Also called Panadol or Tylenol in some countries.
- ↑ "Paracetamol Indications, Uses, Dosage, Drugs Interactions, Side effects". medicaldialogues.in. May 31, 2023. Retrieved 8 November 2024.
- 1 2 3 Rumack B, Matthew H (1975). "Acetaminophen poisoning and toxicity". Pediatrics. 55 (6): 871–76. doi:10.1542/peds.55.6.871. PMID 1134886. S2CID 45739342.
- 1 2 3 4 5 Zezulka A, Wright N (September 1982). "Severe metabolic acidosis early in paracetamol poisoning". British Medical Journal (Clinical Research Ed.). 285 (6345): 851–2. doi:10.1136/bmj.285.6345.851. PMC 1499688. PMID 6811039.
- 1 2 3 4 5 Roth B, Woo O, Blanc P (April 1999). "Early metabolic acidosis and coma after acetaminophen ingestion". Annals of Emergency Medicine. 33 (4): 452–6. doi:10.1016/S0196-0644(99)70312-4. PMID 10092726.
- ↑ "Acute Hepatic Necrosis". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury (Internet). National Institute of Diabetes and Digestive and Kidney Diseases. 4 May 2019. PMID 31689035. Retrieved 19 November 2023.
- 1 2 Heard KJ (July 2008). "Acetylcysteine for Acetaminophen Poisoning". The New England Journal of Medicine. 359 (3): 285–92. doi:10.1056/NEJMct0708278. PMC 2637612. PMID 18635433.
- 1 2 Boutis K, Shannon M (2001). "Nephrotoxicity after acute severe acetaminophen poisoning in adolescents". Journal of Toxicology: Clinical Toxicology. 39 (5): 441–5. doi:10.1081/CLT-100105413. PMID 11545233. S2CID 35456821.
- 1 2 3 4
- Corcoran GB, Mitchell JR, Vaishnav YN, Horning EC (November 1980). "Evidence that acetaminophen and N-hydroxyacetaminophen form a common arylating intermediate, N-acetyl-p-benzoquinoneimine". Molecular Pharmacology. 18 (3): 536–42. PMID 7464816. Archived from the original on 2021-08-28. Retrieved 2025-04-19.
- Rumbeiha WK, Lin YS, Oehme FW (November 1995). "Comparison of N-acetylcysteine and methylene blue, alone or in combination, for treatment of acetaminophen toxicosis in cats". American Journal of Veterinary Research. 56 (11): 1529–33. doi:10.2460/ajvr.1995.56.11.1529. PMID 8585668.
- Richardson, JA (July–September 2000). "Management of acetaminophen and ibuprofen toxicoses in dogs and cats" (PDF). Journal of Veterinary Emergency and Critical Care. 10 (4): 285–291. doi:10.1111/j.1476-4431.2000.tb00013.x. Archived from the original (PDF) on November 22, 2008.
- ↑ "Activated Charcoal - Uses, Side Effects, and More". WebMD. Retrieved April 17, 2025.
- 1 2 3 4 5 Ferri, Fred F. (2016). Ferri's Clinical Advisor 2017 E-Book: 5 Books in 1. Elsevier Health Sciences. p. 11. ISBN 978-0-323-44838-3. Archived from the original on September 10, 2017. Retrieved July 6, 2017.
