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ACETAMENOPHEN TOXICITY. BY: Dina Saad Alagamy Dina Mostafa Shata.
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ACETAMENOPHEN TOXICITY BY: Dina Saad Alagamy Dina Mostafa Shata
A 18 year old female was admitted to the Emergency after trying to commit a suicide by taking a large number of analgesic & antipyretic tablets, she was suffering from sever vomiting, nausea, pallor, anorexia and malaise. She stayed in the emergency for further investigation, after 24 hours lab investigation revealed elevated liver enzymes & serum bilirubin.
What is the possible diagnosis? ACETAMINOPHEN TOXICITY
What is the lab investigation can you do?A) ToxicologicalB)Routine
A)Toxicological Investigation1- plasma acetaminophen level “it's the basic diagnosis even no symptoms” determine 4h post ingestion more than 150mg/ml indicated liver toxicity
2-Rumack Mathew nomogram correlate serum acetaminophen level with time after ingestion it's use only to acute toxicity not for chronic
B) Routine investigation1-liver function test ALT& AST ,bilirubin ,prothrombin should monitored daily ,there's sharp rise of ALT by 3rd day then decline after that2-electrolytes ,glucose ,BUN .3-Renal function test, urine analysis.
Normally: >90% is directly converted to non toxic glucuronide & sulfate conjugates 5% is oxidized by Cytochrome P450 to (N-acetyl-p-benzoquinoneimine) <5% excreted unchanged in urine
In toxicity:Sulphate & glucuronide pathway become saturated Acetaminophen shunt to cytochrome p450 increase NAPQI Glutathione depletion NAPQI remains in its toxic form Hepatic & renal damage
Stage 1: “GIT Irritation” 0.5 – 24 hours post-ingestion
Stage 2: “Apparent recovery”24 – 48 hours post-ingestionsymptoms less sever, patient looks normalincrease SGOT & SGPTIncrease BilirubinProlonged PT
Stage 4: “Actual recovery”5 days – 2 weeksStarting from the 5th dayLiver function test returns to normalHepatic architecture returns to normal with fibrosiswithin 3 months
B)GIT Decontamination1-gastric lavage2-Activated charcoal3-Soduim sulphate cathartics
NAC or Mucomyst 20% Time: 8-10 hours Mechanism :
NAC or Mucomyst 20% Dose : 1) Oral :- Loading dose = 140 mg/kg Maintenance dose = 70 mg/kg every 4h for 17 doses 2)IV infusion :- Loading dose = 150 mg/kg in 200 ml dextrose 5% over 30 min Maintenance dose = 50 mg/kg in 250 ml dextrose 5% over 4h THEN 100 mg/kg in 500 ml dextrose 5 % over 16h
NAC or Mucomyst 20% Indications: Level above the possible risk line Level more20mg/ml &unknown time of ingestion Evidence of hepatic toxicity &history of excessive dose Precautions: Do not stop NAC early if monogram indicated toxic possibility Any dose vomited within 1hour of administration should be repeated If emesis persists anti emetics may be used If evidence of liver injury develops NAC is continued until LFT are improve
D) Enhance Elimination:1-massive ingestion with very high levels & complicated with coma or acidosis2-Acute renal failure