DILI: APAP OD Flashcards
Drug that’s the most responsible for hospitalization
APAP
Predisposing factors for APAP toxicity
2E1 induction (anticonvulsants, isoniazid, chronic alcohol users)
Reduced glutathione stores (malnutrition)
Decreased sulfation and glucuronidation
Symptoms of APAP toxicity
N/V, malaise, pallor, diaphoresis
Liver injury isn’t seen in APAP OD until how much later?
24-36 hours post-ingestion with increases in AST
Peak AST in hepatotoxicity during APAP OD
> 1000 IU/L
Maximal hepatotoxicity occurs in APAP OD how much later after ingestion?
72-96 hours
AST and ALT levels can get to what value in APAP OD?
> 10,000 IU/L
What other lab values will also change in APAP OD?
INR, bilirubin, glucose, lactate, phosphate, pH, may have renal failure
APAP OD can also lead to what complications?
Fulminant hepatic failure and encephalopathy, coma, cerebral edema, and/or hemorrhage
Death from an APAP OD will occur when?
3-5 days after ingestion, but patients who survive will make a full recovery
APAP OD management: when to consider activated charcoal
Patients who present within 1-2 hours post-ingestion
APAP OD management: NAC MoA
glutathione substitute detoxifying NAPQI, serves as a precursor to glutathione → increased glutathione production
NAC efficacy
Nearly complete when administered within 8 hours of APAP OD
How to decide to treat patient with NAC
Based on the APAP serum levels plotted on the Rumack-Matthew nomogram- if the serum levels are to the right of the dotted line, treat with NAC
If APAP level is outside the 4-24 hour window: prior to hour 4
Consider activated charcoal, then reassess at 4 hours to see if NAC is needed
If APAP level is outside the 4-24 hour window: after hour 24
If AST is elevated regardless of APAP level, treat with NAC
If APAP level is outside the 4-24 hour window: after hour 24 or unknown late ingestion with detectable APAP level
NAC therapy
APAP OD: supportive care
IV fluids, management of N/V, hypoglycemia correction, Vitamin K/FFP
IV NAC vs. PO NAC: which one’s better?
They’re both equally efficacious
Features of IV NAC: what happens to the NAC concentrations with IV administration?
Higher systemic NAC concentrations
Features of IV NAC: what diseases/patient populations can you use it in?
More desirable if other organs are affected
Can use in patients with liver failure, pregnancy, inability to tolerate PO
Length of IV dosing protocol
20 hours
ADE of IV NAC
Anaphylactoid reactions (flushing, rash, bronchospasm), can be treated with Benadryl to reduce flushing and restart treatment after
Feature of PO NAC
Gets delivered directly to the liver through portal circulation with high 1st pass extraction –> lower systemic NAC conentrations
Length of PO NAC dosing protocol
72 hours
ADEs of PO NAC
Bad taste and smell (rotten eggs), N/V
Management of PO NAC ADEs
Pretreat with antiemetic, repeat dose in 1 hour if dose is vomited up, solution should be diluted to 5% with a soft drink with the top covered
Toxic APAP dose in adults
≥7.5g
Toxic APAP dose in kids
≥150mg/kg
NAC’s MoA may allow for less production of what?
NAPQI and less 2E1 induction