1. ACETAMENOPHEN TOXICITY
BY:
Dina Saad Alagamy
Dina Mostafa Shata

2. 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.

3. What is the possible diagnosis?
ACETAMINOPHEN TOXICITY

4. What is the lab investigation can you do? A) Toxicological B)Routine

5. A)Toxicological Investigation 1- plasma acetaminophen level “it's the basic diagnosis even no symptoms” determine 4h post ingestion more than 150mg/ml indicated liver toxicity

6. 2-Rumack Mathew nomogram correlate serum acetaminophen level with time after ingestion it's use only to acute toxicity not for chronic

7. B) Routine investigation 1-liver function test ALT& AST ,bilirubin , prothrombin should monitored daily ,there's sharp rise of ALT by 3rd day then decline after that 2-electrolytes ,glucose ,BUN . 3-Renal function test, urine analysis.

8. What is the toxic action of acetaminophen ?

9. Normally: >90% is directly converted to non toxic glucuronide & sulfate conjugates % is oxidized by Cytochrome P450 to (N-acetyl-p-benzoquinoneimine) <5% excreted unchanged in urine

10. In toxicity: Sulphate & glucuronide pathway become saturated Acetaminophen shunt to cytochrome p increase NAPQI Glutathione depletion NAPQI remains in its toxic form Hepatic & renal damage

11. What's the expected clinical presentation?

12. Stage 1: “GIT Irritation” 0.5 – 24 hours post-ingestion

13. Stage 2: “Apparent recovery” 24 – 48 hours post-ingestion symptoms less sever, patient looks normal increase SGOT & SGPT Increase Bilirubin Prolonged PT

14. Stage 3: “Hepatic necrosis” 3 – 5 days post-ingestion

15. Stage 4: “Actual recovery” 5 days – 2 weeks Starting from the 5th day Liver function test returns to normal Hepatic architecture returns to normal with fibrosis within 3 months

16. How to management this case?

17. A)Emergency & Supportive measures 1- 2-

18. B)GIT Decontamination 1-gastric lavage 2-Activated charcoal 3-Soduim sulphate cathartics

19. C)Antidotes : 1-NAC or Mucomyst 20% 2-Methionine tab 250 mg

20. NAC or Mucomyst 20%
Time: hours
Mechanism :

21. Dose : 1) Oral :- 2)IV infusion :- NAC or Mucomyst 20%
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

22. Indications: Precautions: NAC or Mucomyst 20%
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

23. D) Enhance Elimination: 1-massive ingestion with very high levels & complicated with coma or acidosis 2-Acute renal failure