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GI/Hepatic Final > APAP Toxicity and Fulminant Liver failure > Flashcards

APAP Toxicity and Fulminant Liver failure Flashcards

1
Q

What is the pediatric dose for APAP?

A

10-15 mg/kg/dose q4-6h (max 90 mg/kg/d)

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2
Q

What is the adult dosing for APAP?

A

325-1,000 mg q4-6h (max 4,000 mg daily)

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3
Q

What is the time to Cpeak for a normal therapeutic dose of APAP?

A

0.5-2 hours

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4
Q

What is the time to Cpeak for an IR APAP product?

A

4 hours

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5
Q

What is the time to Cpeak for an ER APAP product?

A

> 4 hours

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6
Q

What is the half-life for APAP?

A

2-4 hours

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7
Q

What is the therapeutic serum concentration for APAP?

A

10-20 mcg/ml

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8
Q

How is APAP metabolized?

A

90% is metabolized to sulfate and glucuronide conjugates
5% is excreted in the urine unchanged
5% metabolized by 2E1 to NAPQI (hepatotoxic)

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9
Q

What is the mechanism of APAP toxicity?

A

Sulfate and guluronide stores become saturated and a higher percentage of the ingested dose is metabolized by 2E1 to the toxic metabolite NAPQI
NAPQI interacts with hepatocellular sulfhydryl compounds on hepatocytes to cause hepatic necrosis
Renal toxicity ranging from oliguria to acute renal failure may also occur d/t direct effects of NAPQI on the renal system or hepatic injury leading to hepatorenal syndrome

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10
Q

How many stages of APAP toxicity are there?

A

4

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11
Q

What is stage I APAP toxicity?

A

First 24 hours
N/V, diaphoresis, pallor, lethargy, malaise; some pts asymptomatic
Labs typically normal

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12
Q

What is stage II APAP toxicity?

A 
24-72 hours
Stage I sx resolve and pr appears to improve
LFTs begin to increase
Increase PT, T bili, BUN, SCr
RUQ pain, liver enlargement, tenderness
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13
Q

What is stage III APAP toxicity

A

72-96 hours
LFTs peak
Stage I sx reappear w/jaundice, hepatic encephalopathy, and potential bleeding
Continued/worsening renal function

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14
Q

What is stage IV APAP toxicity?

A

4 days - 2 weeks
Recovery phase
Complete liver histological recovery w/in 3 months (no chronic liver dysfunction)
Renal function returns to normal (1-4 weeks)

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15
Q

What is the dosing for an acute APAP OD?

A 
>/= 7.5 g in adolescents/adult
>/= 150 mg/kg in children
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16
Q

What is the dosing for chronic APAP overdose?

A

> 4 g/d in adults

> 75-90 mg/kg/d in children

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17
Q

What are the RFs for hepatotoxicity from APAP OD?

A

Increased activity of CYP450
Depleted hepatic glutathione stores
Decreased capacity for glucuronidation

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18
Q

What can cause increased activity of CYP450?

A 
Chronic alcohol use (may decrease the risk of hepatotoxicity d/t competitive substrate for 2E1)
Genetic polymorphism of 2E1 gene (develop toxicity at lower APAP doses)
2E1 inducers (carbamazepine, phenobarb, phenytoin, rifampin, isoniazid)
19
Q

What can cause depleted glutathione stores?

A

Fasting

Chronic alcohol use

20
Q

What can cause decreased capacity for glucuronidation?

A

Bactrim

Zidovudine

21
Q

What is the treatment for chronic APAP OD?

A

Acetylcysteine

22
Q

What is acetylcysteine’s MOA?

A

Restoring

23
Q

What are acetylcysteine medications?

A

Oral: Mucomyst
IV: Acetdate

24
Q

How is mucomyst administered?

A

Dilute doses to a 5% concentrations with juice or water to improve palatability
Also cover the cup and drink through straw

25
Q

Which patient’s are acetadote reserved for?

A

Refractory vomiting
Intolerability to oral administration
GI bleed or obstruction
Encephalopathy

26
Q

What is the IV duration of NAC?

A

21

27
Q

What are the ADRs of IV NAC?

A

Anaphylactoid reactions

Acute flushing and erythema in the first hour of the infusion that typically resolves spontaneously

28
Q

What is the oral NAC duration?

A

72 hours

29
Q

What do we give with oral NAC?

A

Oral causes N/V

Antiemetics: metoclopramide, zofran, droperidol

30
Q

When do we give activated charcoal to patients?

A

50g to all adult pts presenting w/in 4 hours of ingestion, unless CI
May be useful beyond 4 hours

31
Q

When do we treat with NAC?

A

Serum APAP concentration drawn at 4 hours or more after a single acute ingestion is above the treatment line of the nomogram
Serum APAP concentration is unavailable or will not return w/in 8 hours of time of ingestion and APAP ingestion is suspected
There is evidence of ANY hepatotoxicity w/a h/o APAP ingestion
Patient reports or clinician suspects repeated excessive APAP ingestions, patient has RFs for APAP-induced hepatotoxicity, and the serum APAP concentration is greater than 10 mcg/mL

32
Q

Who do we treat with oral NAC?

A

Non-pregnant
Intact GI tract
No evidence of hepatotoxicity

33
Q

Who do we give IV NAC?

A

Pregnant
Evidence of hepatotoxicity
Unable to tolerate oral NAC
Medical condition precluding oral administration

34
Q

What is the general presentation of fulminant liver failure?

A

Jaundice
Encephalopathy leading to rapid onset of altered mental status (may progress quickly to coma)
Prolonged PT
Elevated aminotransferases

35
Q

What are the causes of fulminant liver failure?

A 
Drug toxicity (APAP most common)
Viral Hep (C>B) - second most common cause
Other causes
36
Q

What are other causes of fulminant liver failure?

A 
HSV (1&2)
Budd-chiari syndrome
Wilson disease
Acute fatty liver of pregnancy
Acute ischemic injury ("shock liver")
Mushroom poisoning
Toxins
Reye's syndrome
Automimmune hepatitis
Lymphoma
37
Q

What is the management of fulminant liver failure?

A

Supportive!

Transport to transplant center

38
Q

What are the complications of fulminant liver failure?

A 
Respiratory failure
Cerebral edema
Coagulation defects
Hemodynamic instability
Hepatorenal syndrome
Nutrition and metabolic effects
Infectious complications
39
Q

How do we treat respiratory failure?

A

Ventilator

40
Q

How do we treat cerebral edema?

A

Mannitol for increased ICP

Lactulose decreases ammonia levels

41
Q

How de we treat coagulation defects?

A

Vit K
Fresh frozen plasma or platelets
Factor VIIa

42
Q

How is nutrition and metabolism affected in FLF?

A

Electrolytes (hypo-ka/mg, phosphatemia, Na are common)
Hypoglycemia
Protein and calcoric maintenance

43
Q

How does FLF lead to infectious complications?

A

Impaired cell-mediated and humoral immunity

GI/Hepatic Final (6 decks)

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