DILI: APAP OD

Question 1

Drug that’s the most responsible for hospitalization

Answer 1

APAP

Question 2

Predisposing factors for APAP toxicity

Answer 2

2E1 induction (anticonvulsants, isoniazid, chronic alcohol users)
Reduced glutathione stores (malnutrition)
Decreased sulfation and glucuronidation

Question 3

Symptoms of APAP toxicity

Answer 3

N/V, malaise, pallor, diaphoresis

Question 4

Liver injury isn’t seen in APAP OD until how much later?

Answer 4

24-36 hours post-ingestion with increases in AST

Question 5

Peak AST in hepatotoxicity during APAP OD

Answer 5

> 1000 IU/L

Question 6

Maximal hepatotoxicity occurs in APAP OD how much later after ingestion?

Answer 6

72-96 hours

Question 7

AST and ALT levels can get to what value in APAP OD?

Answer 7

> 10,000 IU/L

Question 8

What other lab values will also change in APAP OD?

Answer 8

INR, bilirubin, glucose, lactate, phosphate, pH, may have renal failure

Question 9

APAP OD can also lead to what complications?

Answer 9

Fulminant hepatic failure and encephalopathy, coma, cerebral edema, and/or hemorrhage

Question 10

Death from an APAP OD will occur when?

Answer 10

3-5 days after ingestion, but patients who survive will make a full recovery

Question 11

APAP OD management: when to consider activated charcoal

Answer 11

Patients who present within 1-2 hours post-ingestion

Question 12

APAP OD management: NAC MoA

Answer 12

glutathione substitute detoxifying NAPQI, serves as a precursor to glutathione → increased glutathione production

Question 13

NAC efficacy

Answer 13

Nearly complete when administered within 8 hours of APAP OD

Question 14

How to decide to treat patient with NAC

Answer 14

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

Question 15

If APAP level is outside the 4-24 hour window: prior to hour 4

Answer 15

Consider activated charcoal, then reassess at 4 hours to see if NAC is needed

Question 16

If APAP level is outside the 4-24 hour window: after hour 24

Answer 16

If AST is elevated regardless of APAP level, treat with NAC

Question 17

If APAP level is outside the 4-24 hour window: after hour 24 or unknown late ingestion with detectable APAP level

Answer 17

NAC therapy

Question 18

APAP OD: supportive care

Answer 18

IV fluids, management of N/V, hypoglycemia correction, Vitamin K/FFP

Question 19

IV NAC vs. PO NAC: which one’s better?

Answer 19

They’re both equally efficacious

Question 20

Features of IV NAC: what happens to the NAC concentrations with IV administration?

Answer 20

Higher systemic NAC concentrations

Question 21

Features of IV NAC: what diseases/patient populations can you use it in?

Answer 21

More desirable if other organs are affected
Can use in patients with liver failure, pregnancy, inability to tolerate PO

Question 22

Length of IV dosing protocol

Answer 22

20 hours

Question 23

ADE of IV NAC

Answer 23

Anaphylactoid reactions (flushing, rash, bronchospasm), can be treated with Benadryl to reduce flushing and restart treatment after

Question 24

Feature of PO NAC

Answer 24

Gets delivered directly to the liver through portal circulation with high 1st pass extraction –> lower systemic NAC conentrations

Question 25

Length of PO NAC dosing protocol

Answer 25

72 hours

Question 26

ADEs of PO NAC

Answer 26

Bad taste and smell (rotten eggs), N/V

Question 27

Management of PO NAC ADEs

Answer 27

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

Question 28

Toxic APAP dose in adults

Answer 28

≥7.5g

Question 29

Toxic APAP dose in kids

Answer 29

≥150mg/kg

Question 30

NAC’s MoA may allow for less production of what?

Answer 30

NAPQI and less 2E1 induction