S15C184 - Acetaminophen

Question 1

Max daily dose of APAP in children:

Answer 1

75mg/kg

Question 2

Peak serum APAP occurs how many hours after an OD?

Answer 2

2h (longer depending on preparation of drug)

Question 3

Toxic metabolite of APAP

Answer 3

NAPQI, in OD hepatic gluoronidaton/sulfation is saturated, so cyt P-450 tries to metabolize NAPQI depleting stores of glutathione and NAPQI goes and binds with other things leading to cell necrosis

Question 4

Clinical presentation APAP OD

Answer 4

• anorexia, n/v, malaise
• hypokalemia may be seen w/in 24h
• day 2, symptoms improve, hepatotoxicity symptoms start (RUQ pain, elevated AST/ALT)
• day 3/4- fulminant hepatic failure (or resolution), metabolic acidosis, c oagulopathy, renal failure, encephalopathy, GI Sx
• recovery occurs at 2w, resolution by 1-3mo if they don’t die

Question 5

Who is at greater risk of toxicity?

Answer 5

• alcoholics
• those on anticonvulsants
• antituberculous meds

-children are actually at less risk

Question 6

Toxic dose of APAP

Answer 6

> 10g or 200mg/kg i single ingestion or over 24h

-or >6g or 150mg/kg per 24h period for 2 consecutive days

Question 7

Name of APAP nomogram

Answer 7

Rumack-Matthew

Question 8

Nomogram applies to what timeframe

Answer 8

4-24h post ingestion
-if above line there is a 60% risk of hepatotoxicity and 5% mortality, if above second line then 90% risk of hepatotoxicity, below line is a 1% risk

Question 9

Tx for APAP OD

Answer 9

ABC
Decontamination - activate charcoal
E
Find an antidote: NAC

Question 10

NAC

Answer 10

• if given w/in 8h it is nearly 100% effective in preventing hepatotoxicity
• given for 72h
• load with 150mg/kg over 15 mins-1h, then 50mg/kg over 4h, then 100mg/kg over 16h
• IV anaphylactoid rxn: occurs in first 2h of adminsitration, tx with benadryl and slow/stop infusion
• continue infusion for 20h or longer until APAP undetectable and transaminases are normal or decreasing