2. Acetaminophen is a non-narcotic analgesic, antipyretic, weak anti-inflammatory activity.  COX-3 in CNS   PGs (brain)  COX-3 in CNS   PGs (brain) Pyrogen  PG  temp. regulatory centres  hyperthermias.  COX-1 & COX-2 in periphery (mild effect)  COX-1 & COX-2 in periphery (mild effect)

3. Peptic ulcer.Peptic ulcer. Bronchial asthma.Bronchial asthma. Viral infection in children. (Aspirin may lead to Reye’s syndrome (hepatic encephalopathy)).Viral infection in children. (Aspirin may lead to Reye’s syndrome (hepatic encephalopathy)). Toxic dose: more than 7.5g as a single doseToxic dose: more than 7.5g as a single dose Hepatotoxic dose: starts at 140 mg/kgHepatotoxic dose: starts at 140 mg/kg

4. ROS Bind with macromolecules in liver cells (lipid, protein, DNA)  necrosis Chandok N, Watt K D S Mayo Clin Proc. 2010;85:451-458 GSH Mercapturic acid and cysteine conjugates

8. Severe liver damage that might necessitate LIVER transplantation can be suspected in the following cases: 1.Severe acidosis (pH <7.3) 2.Prothrombin time > 50s (USA) or 100s (UK) 3.Grade III/IV hepatic encephalopathy 4.Serum creatinine > 3.3 mg/dL (300  M/L) 5.Bilirubin > 4mg/dL

13. Keep in mind the following

14. W.R. is a 40-year old, 75 kg alcoholic male brought to the emergency department six hours after ingesting fifty 500 mg acetaminophen tablets. At home, he was given syrup of ipecac to induce emesis, but no undissolved tablets were seen. The patient’s only complaints were nausea, vomiting, and anorexia. He was given an oral dose of activated charcoal 60gm and magnesium citrate 300mL. Physical examination was unremarkable; a blood sample for measurement of the acetaminophen serum concentration was obtained.

15. What are the symptoms of acetaminophen poisoning? Were W.R. symptoms consistent with an acute intoxication? Symptoms: (see stages I-IV)Symptoms: (see stages I-IV) The symptoms are consistent with acute intoxication as the patient suffered from stage I symptoms (nausea, vomiting, and anorexia)The symptoms are consistent with acute intoxication as the patient suffered from stage I symptoms (nausea, vomiting, and anorexia)

16. Describe the mechanism(s) of acetaminophen-induced hepatotoxicity and assess W.R. risk for the development of this complication. Mechanisms: (see NAPQI formation)Mechanisms: (see NAPQI formation) W.R. ingested 330 mg/kg of acetaminophen ((50 X 500)/75).W.R. ingested 330 mg/kg of acetaminophen ((50 X 500)/75). Ingestions of this magnitude are usually associated with hepatic necrosis, if antidotal treatment is not initiated or is delayed.Ingestions of this magnitude are usually associated with hepatic necrosis, if antidotal treatment is not initiated or is delayed. If W.R.’s serum concentration was less than 120  g/ml four to six hours after ingestion, his risk for development of hepatic necrosis would be estimated as minimal by the nomogram.If W.R.’s serum concentration was less than 120  g/ml four to six hours after ingestion, his risk for development of hepatic necrosis would be estimated as minimal by the nomogram.nomogram However, hepatotoxicity has been reported in alcoholics after repeated therapeutic doses of acetaminophen and hepatotoxicity could occur in W.R. even with a reportedly “safe” serum concentration.However, hepatotoxicity has been reported in alcoholics after repeated therapeutic doses of acetaminophen and hepatotoxicity could occur in W.R. even with a reportedly “safe” serum concentration. Alcoholics appear to be at increased risk for acetaminophen-induced hepatotoxicity, because an alcohol-induced cytochrome P 450 mixed- function oxidase system results in increased formation of the reactive intermediate.Alcoholics appear to be at increased risk for acetaminophen-induced hepatotoxicity, because an alcohol-induced cytochrome P 450 mixed- function oxidase system results in increased formation of the reactive intermediate. Also, alcohol-associated malnutrition can result in decreased hepatic glutathione stores.Also, alcohol-associated malnutrition can result in decreased hepatic glutathione stores.

17. The acetaminophen serum concentration obtained on admission was 295  g/mL. What additional treatment is indicated for W R.? 295  g/mL295  g/mL The patient should immediately receive an antidotal treatment and should be closely monitored for possible application of enhanced elimination techniques.