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wikitox:2.1.1.1_acetaminophen [2024/04/23 19:56] – kharriswikitox:2.1.1.1_acetaminophen [2025/02/24 21:27] (current) – kharris
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-Link to [[:wikitox:2.1.1.1_acetaminophen_paracetamol_teaching_resources|Acetaminophen Paracetamol Teaching Resources]]\\ +====== Paracetamol (acetaminophen) ======
-Link to [[:wikitox:problems_for_discussion_1_paracetamol|Problems for Discussion]]\\ +
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- <font 36px/inherit;;#b12c04;;inherit>Paracetamol (Acetaminophen)</font> +
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 ===== Overview ===== ===== Overview =====
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 Paracetamol is a readily available analgesic and is commonly taken in overdose. It is available in immediate and slow-release preparations as well as in combination products often containing opioids, caffeine or ibuprofen. Several strengths of liquid paracetamol are also available. Paracetamol is a readily available analgesic and is commonly taken in overdose. It is available in immediate and slow-release preparations as well as in combination products often containing opioids, caffeine or ibuprofen. Several strengths of liquid paracetamol are also available.
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 In overdose, glutathione stores are depleted, and NAPQI instead binds to sulfhydryl containing proteins in the liver cells and causes lipid peroxidation, disrupting the cell membrane. These events eventually lead to cell death. Any organ with P450 enzymes can suffer damage, particularly the liver and kidney, but the heart and pancreas can also be affected. In overdose, glutathione stores are depleted, and NAPQI instead binds to sulfhydryl containing proteins in the liver cells and causes lipid peroxidation, disrupting the cell membrane. These events eventually lead to cell death. Any organ with P450 enzymes can suffer damage, particularly the liver and kidney, but the heart and pancreas can also be affected.
  
-In massive ingestion with very high paracetamol concentrations (generally >600mg/L) patients can develop altered level of consciousness, including coma, and a lactic acidosis. This results from mitochondiral toxicity due to inhibition of the electron transport chain. This resolves as the paracetamol level reduced, but in some cases, if the acidosis is severe, dialysis may be required. +In massive ingestion with very high paracetamol concentrations (generally >600mg/L) patients can develop altered level of consciousness, including coma, and a lactic acidosis. This results from mitochondrial toxicity due to inhibition of the electron transport chain. This resolves as the paracetamol level reduced, but in some cases, if the acidosis is severe, dialysis may be required.
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 ===== Risk Assessment ===== ===== Risk Assessment =====
  
-There are numerous guidelines published for the treatment of paracetamol related toxicity. The risk assessment and treatment outlines in this monograph are based on the Australian Guidelines for the Treatment of Paracetamol Toxicity ( +There are numerous guidelines published for the treatment of paracetamol related toxicity. The risk assessment and treatment outlines in this monograph are based on the {{:wikitox:chiew_-_mja_updated_guidelines_for_the_management_of_paracetamol_poisoning_in_australia.pdf|Australian Guidelines for the Treatment of Paracetamol Toxicity}}.
- <font inherit/inherit;;inherit;;#f1c40f>add link)</font> .+
  
 An accurate risk assessment is crucial in determining the need for investigation and treatment following overdose. Important information in the risk assessment includes: An accurate risk assessment is crucial in determining the need for investigation and treatment following overdose. Important information in the risk assessment includes:
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   * Clinical and laboratory features of acute liver injury (late).   * Clinical and laboratory features of acute liver injury (late).
  
-[[:wikitox:paracetamol-picture1.png?id=wikitox:2.1.1.1_acetaminophen&media=wikitox:paracetamol-picture1.png|{{:wikitox:paracetamol-picture1.png?nolink&}}]] <font 20px/inherit;;#c12b04;;inherit>__Acute single ingestion of **immediate release paracetamol**__</font>+[[:wikitox:paracetamol-picture1.png?id=wikitox:2.1.1.1_acetaminophen&media=wikitox:paracetamol-picture1.png|{{:wikitox:paracetamol-picture1.png?direct&}}]] 
 + <font 20px/inherit;;#c12b04;;inherit>__Acute single ingestion of **immediate release paracetamol**__</font>
  
-An acute single ingestion of paraetamol that may be associated with acute liver injury if defined as ** <font 11.0pt/inherit;;inherit;;inherit>≥10g or ≥200mg/kg (whichever is less).</font> **+An acute single ingestion of paracetamol that may be associated with acute liver injury if defined as ** <font 11.0pt/inherit;;inherit;;inherit>≥10g or ≥200mg/kg (whichever is less).</font> **
  
 For acute single dose ingestion of immediate release paracetamol with a known time of ingestion, the paracetamol treatment nomogram (Image 2) can be used to determine the need for NAC therapy. For acute single dose ingestion of immediate release paracetamol with a known time of ingestion, the paracetamol treatment nomogram (Image 2) can be used to determine the need for NAC therapy.
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   * ≥ 10g or ≥ 200mg/kg (whichever is less) over a 24hr period   * ≥ 10g or ≥ 200mg/kg (whichever is less) over a 24hr period
   * ≥ 12g or ≥ 300mg/kg (whichever is less) over a 48hr period   * ≥ 12g or ≥ 300mg/kg (whichever is less) over a 48hr period
-  * ≥ a daily therapeutic dose per day for more than 48hr in pateints who also have abdominal pain or nausea or vomiting+  * ≥ a daily therapeutic dose per day for more than 48hr in patients who also have abdominal pain or nausea or vomiting
  
 //Image 5. Click to enlarge.// //Image 5. Click to enlarge.//
  
 //{{  :wikitox:paraflowrsti.png?direct&200  }}// //{{  :wikitox:paraflowrsti.png?direct&200  }}//
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 ===== Kinectics in Overdose ===== ===== Kinectics in Overdose =====
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   * **Bloods gas:**  for large ingestions with concern for mitochondrial toxicity or for monitoring for acidosis in hepatotoxicity.   * **Bloods gas:**  for large ingestions with concern for mitochondrial toxicity or for monitoring for acidosis in hepatotoxicity.
   * **Coagulation studies:**  to monitor synthetic function if liver injury present   * **Coagulation studies:**  to monitor synthetic function if liver injury present
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 ===== Treatment ===== ===== Treatment =====
  
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 ==== Decontamination ==== ==== Decontamination ====
- <font inherit/inherit;;#c12b04;;inherit>Acute Immediate Release ingestion</font> : 50g activated charcoal should be offered to patients who have presented within 2 hours of ingestion a potential toxic dose. If a large ingestion (>30g or >500mg/kg) charcoal can be offered up to 4 hours post ingestion. + 
- <font inherit/inherit;;#c12b04;;inherit>Modified release paracetamol ingestions</font> : 50g activated charcoal should be offered to patients who have presented within 4 hours of ingestion of a potential toxic dose. In large ingestion (>30g or >500mg/kg) absorption may continue up to 24 hours and so charcoal can be offered up to 24 hours post ingestion. As per the treatment guideline (Box 4) a second paracetamol level 4 hours after the first should be taken – if this is static or increasing from the first level, offer a second 50g dose of activated charcoal.+Acute Immediate Release ingestion : 50g activated charcoal should be offered to patients who have presented within 2 hours of ingestion a potential toxic dose. If a large ingestion (>30g or >500mg/kg) charcoal can be offered up to 4 hours post ingestion. Modified release paracetamol ingestions : 50g activated charcoal should be offered to patients who have presented within 4 hours of ingestion of a potential toxic dose. In large ingestion (>30g or >500mg/kg) absorption may continue up to 24 hours and so charcoal can be offered up to 24 hours post ingestion. As per the treatment guideline (Box 4) a second paracetamol level 4 hours after the first should be taken – if this is static or increasing from the first level, offer a second 50g dose of activated charcoal.
  
 ==== Enhanced Elimination ==== ==== Enhanced Elimination ====