ACETAMINOPHEN TOXICITY

1. ACETAMINOPHEN TOXICITY گروه طب اورژانس دانشگاه علوم پزشکی اصفهان

2. Acetaminophen • Tab.acetaminophen 325mg • Tab.acetaminophen codein 500mg • Tab adult cold 325mg • Tab. Child cold 80mg • Oral suspension 120mg/5ml • Elixir 120mg/5ml • Drop 100mg/ml • Suppositories 325mg &125mg • IV Apotel 1 G

3. Maximum daily dosage in Adult • 4 g in short duration • 2.5 g in long duration • 1.5 g in child 6-12 year • 500 mg in child 3-6 year

4. The most common indication for liver transplantation In UK

5. ABSORPTION 1 HOUR

6. HALF LIFE 2.5-4 h

7. Connection to plasma proteins 10%

8. VOLUME OF DISTRIBUTION 0.9 L/kg

9. METABOLISM • SULFATION&GLOCORONIDATION80% • CYTOCHROM P-450 20%

10. N-ACETYL-P-BANZOQUINONEIMINE NAPQI

11. HALF LIFE of NAPQI 0.000000001S

12. METABOLISM OF NAPQI GLOTATIUNE

13. LIVER GLOTATIUNE 30%

14. Risk factors • Age • Fasting • alcohol

15. MINIMUME OF SINGLETOXIC DOSE 7.5gr in adult 140 mg/kg

16. CLINICAL PRESENTATION • During the first 24 h after exposure (stage 1): minimal signs and symptoms • By days 2 to 3 (stage2): clinical signs of hepatotoxicity, RUQ abdominal pain and tenderness,and abnormal laboratory tests • By days 3 to 4 (stage 3):fulminant hepatic failure metabolic acidosis, coagulopathy, renal failure, encephalopathy,and recurrent GI symptoms. • over the next week (stage 4): complete resolution of hepatic dysfunction in survivors.

17. Symptom & sign in 24 hours • Nausea • Vomiting • Lethargy • Malaise

18. 24-48 HOURS • INCREASE ALT • INCREASE AST • Increase PT • Increase bilirubin • Pain in RUQ

19. 72-96 HOURS • LIVER NECROSIS • Renal failure • Encephalopathy • Coagulopathy

20. 5 - 14 days Liver heals with appropriatetreatment

21. SEVERE HEPATOTOXICITY 3.5%

22. 50% LIVER TRANSPLANTATION OR DEATH

23. RISK OF HEPATOTOXICITY • POSSIBLE >I50 micro gr/ml • PROBABLE >200 micro gr/ml • HIGH RISK >300 micro gr/ml

24. Rumack-matthew nomogram

25. DIAGNOSIS: • Ingestion of greater than 140 mg/kg APAP or greater than 7.5 g within a 24-h confirmation • Rumack-Matthew nomogram • the nomogram only applies to an APAP level obtained after 4 h postingestion and before 24 h • An initial level below the nomogram line may rarely "cross the line”

26. Level of acetaminophen in serum After 4 hours from used

27. Risk factors • PH <7.30 • PT>100 S • CREATININ >3.3mg/dl

28. GENERAL TREATMENTS • CAB • GASTRIC WASHING • CHARCOHL single dose • SORBITOL

29. N-ACETYL CYSTEIN N.A.C.

30. NAC: • averts toxicity by preventing the binding of NAPQI to hepatic macromolecules by acting as a glutathione precursor or substitute • as an antioxidant, decreasing neutrophil infiltration, improving microcirculatory blood flow, or increasing tissue oxygen delivery and extraction.

31. INCREASE OF GLOTATIUNSYNTHESIS Increase AcetaminophenMetabolism P-450 Path Way

32. AMP N.A.C 2 gr

33. Protocol of prescription • 150 mg/kg in 200 ml D5W IV in 15 minutes • 50 mg/kg in 500 ml D5W IV in 4 hours • 100 mg/kg in 1000 ml D5W IV in 16 hours

34. ORAL N.A.C. 140mg/kg from solution 5% Then 70mg/kg Q/4h for 17 dose

35. Antidote therapy: • The standard 72-h oral NAC regimen • Intravenous NAC regimens(refractory vomiting,fulminant hepatitis,…) • Although NAC is adsorbed by activated charcoal, there is no evidence that activated charcoal inhibits the clinical effectiveness of NAC • In pregnancy

36. Side effect of N.A.C • Nausea • Vomiting • Allergic side effects

37. Paraclinic evaluation • Serum level of acetaminophen • AST &ALT • Bilirubin • PT • Cratinin &BUN • Pregnancy test