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Clin Tox Exam 1 > Acetaminophen > Flashcards

Acetaminophen Flashcards

1
Q

Therapeutic dose of Acetaminophen

A

325-1000 mg (10-15 mg/kg/dose for children) Q4H

Max: 4 g (75 mg/kg/day in children)

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2
Q

Adult Acute Toxic Dose

A

> /= 10 grams or 200 mg/kg, which ever is less

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3
Q

Adult Chronic Toxic Dose

A

For >48 hours: >6 g/day or 150 mg/kg/day

If risk factors: >4 g/day or 100 mg/kg/day

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4
Q

Children Acute Toxic Dose

A

> 200 mg/kg

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5
Q

**Risk Factors influencing hepatotoxicity

A 
Chronic alcohol ingestion
Meds/herbs that induce 2E1 (rifampicin, phenobarbital, St. John's wort)
Meds that compete with hepatic glucorunidation (bactrim and zidovudine)
Gilbert's syndrome
Malnutrition
Fasting state
Chronic liver disease
Advanced age
Pregnancy
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6
Q

Acetaminophen Metabolism

A

Sulfation (30%)
Glucoronidation (60%)
2E1 (10%)

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7
Q

2E1 Pathways

A

Acetaminophen –> NAPQI (toxic metabolite)

Then broken down by glutathione to cysteine and mercapturic acid which can be excreted renally

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8
Q

Glutathione Levels and Timing

A

As long as our body have at least >30% glutathione, there shouldn’t be toxicity
BUT glutathione is completely depleted in 6-8 hours

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9
Q

Consequences of Acetaminophen Toxicity

A

Liver damage and possible kidney damage through necorsis (centrilobular hepatic and proximal convoluted tubule)

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10
Q

Centrilobular Necrosis Mechanism

A

NAPQI freely binds to cysteine which causes oxidation damage and necrossi of the central region of the liver

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11
Q

APAP Peak Effects

A

Oral: 30 minutes
IV: 15 minutes
Toxic Doses: 4 hours!!!!

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12
Q

APAP Absorption

A

Small intestine

Complete within 1.5-2.5 hours

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13
Q

APAP Protein binding and Elimination

A

10-25% PB

2% excreted unchanged and its half-life is 2-3 hours but at toxic doses the half life is 4-12 hours

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14
Q

***Acetaminophen Toxidrome Phase 1

A

0-24 hours
Asymptomatic
N/V and anorexia
+/- malaise, diaphoresis

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15
Q

***Acetaminophen Toxidrome Phase 2

A

24-72 hours
Decreased N/V and anorexia
Increased AST (liver damage)
+/- Right upper quadrant pain (inflammed liver), increased bulirubin, prolong PT, decreased renal function

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16
Q

***Acetaminophen Toxidrome Phase 3

A

72-96 Hours
Hepatic necrosis, jaundice, increase PT/INR, encephalopathy, renal failure
Death due to multi-organ failure

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17
Q

***Acetaminophen Toxidrome Phase 4

A

4-14 days
AKA recovery phase
Complete resolution of hepatic dysfunction without fibrosis

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18
Q

Excessive CYP activity can be caused by?

A 
Fasting
Drugs
Chronic alcohol ingestion 
Genetics
All lead to increased NAPQI metabolites
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19
Q

Define Gilbert’s disease

A

Decreased compatibility for glucuronidation and sulfation

20
Q

GSH-dependent pathways?

A

Chronic liver disease
Chronic alcohol ingestion
Malnutrition
All lead to GSH depletion

21
Q

Acute Alcohol + APAP

A

Alcohol competes wtih APAP for 2E1 binding site and decrease APAP conversion to NAPQI
- ACUTE = PROTECTIVE

22
Q

Effects of Chronic Alcohol Co-Ingestion

A

Acetaldehyde accumulation inhibiting glutathione synthetase
Induced GGT –> increased glutathione degradation
Poor dietary intake of glutathione
Induced 2E1

23
Q

Systematic Management of APAP Toxicity

A 
Emergency Stabilization
Patient Evaluation
Treatment to reduce absorption
Measures to improve elimination
Antidote
Continuing care and disposition
24
Q

ABCDEF

A 
Airway
Breathing
Circulation BP, Pulse
DONT (dextrose, oxygen)
Exposure
Fever
25
Q

Diagnostic Testing for APA

A

Taken 4 hours after ingestion!!!!
AST/ALT elevated –> treat regardless
AST/ALT WNL + APAP below treatment line –> observe
- Bili and SCr
- PT/INR to assess degree of liver injury

26
Q

Rumack-Matthew Nonogram

A

NEEDS TO BE IN mcg/mL
Start more than 4 hours since ingestion and repeat 4 hours later
Above the line = AST/ALT > 100 –> increased risk of hepatotoxicity –> TREAT

27
Q

Treatment to reduce absorption

A

Gastric emptying: NO

Activated Charcoal: YES

28
Q

Measures to improve elimination:

A

NO

29
Q

Specific Antidote for APAP

A

N-Acetylcystein (NAC)

30
Q

NAC =

A

GLutathione precursor and substitute
Provides sulfhydryl group for sulfate conjugation
Antioxidant

31
Q

NAC Indication

A
  • APAP in the potentially toxic range on the RM nonogram
  • History suggests an acute ingestion of 150 mg/kg and/or results could not be obtained within 8 hours
  • Measurable APAP 24 hours after ingestion
  • Evidence of hepatic injury
  • Chronic APAP abuser with elevated AST or APAP > 10 mcg/mL
32
Q

***When do you start NAC

A

START WITHIN 6-8 HOURS OF INGESTION - delay decreases effectiveness*****

33
Q

NAC MOA

A

Increases sulfation and blocks 2E1 before complete depletion of glutathione (within 6-8 hours)

34
Q

NAC + Pregnacy

A

Category B
Crosses placenta
Gives the baby some protection too so get on board ASAP

35
Q

IV NAC Name, AE, Indication, Dose

A

Acetaladote
Anaphylatic reaction, bronchospams
I: pregnant, fulminant hepatic failure, intractable vomiting, altered mental status
D: 300 mg/kg over 20 hours

36
Q

Oral NAC Name, AE, Indication, Dose

A

Mucomyst
Bad smell and taste –> N/V
Asthma and no indication for IV
D: 1330 mg/kg NAC over 72 hours

37
Q

NAC Note

A

Repeat dose if emesis occurs within 1 hours of administration
Solution should be DILUTED to 5% and can be mixed with soft drink to lessen the bad taste

38
Q

When to d/c oral dose?

A

71 hours, d/c when: LFTs are trending towards normal, coagulation studies/pH/bilirubin are WNL, APAP no longer present, continuing would be harmful

39
Q

When to d/c IV dose

A

21 hours, d/c when: LFT and coagulation studies are normal, APA undetectable in serum
If neither of these, continue for at least 24 hours and repeat labs Q24H

40
Q

Continuing Care

A

Psych eval
Monitoring effifacy (daily assessment of APAP, AST/ALT, total bilirubin and INR
Monitoring toxicity
Last: liver transplant

41
Q

AST/ALT + Treatment

A

May peak at several thousand units even with NAC therapy

42
Q

Monitoring with Oral NAC

A

Must be retained for 1 hour after dose

Protracted vomiting - treat with antiemetic like ondansetron, feeding tube or switch to IV

43
Q

Monitoring with IV NAC

A

Allergy or anaphylactic reaction

Administer slowly over 1 hour

44
Q

Pharmacist Role

A 
Do not use APAP or ACET on label
Use warning lables
Check for multiple sources of APAP
Look for drug interaction
Watch opioid tolerance increased usage of Rx
Warn the patient
In-store flyers/signs
Education
45
Q

Education to Patients

A 
Read labels
Avoid OTC APAP
Don't go over max dose
Never take more than 1 OTC APAP product
Store away from children
Measure liquids accurately
Use child's weight then age

Clin Tox Exam 1 (5 decks)

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