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Toxi Lab > Paracetamol > Flashcards

Paracetamol Flashcards

1
Q

(Year) First clinical use
by von Mering

A

1893

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2
Q

(Year) Extensive
medical use as
prescription drug

A

1947

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3
Q

(Year) Commercial
availability in US

A

1950

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4
Q

(Year) Became OTC

A

1960

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5
Q

(year) Discovery of
hepatotoxicity
as ADR

A

1966

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6
Q

(Year) Became mainstay
analgesic and
antipyretic

A

1980s

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7
Q

T/F: Paracetamol has no inflammatory property

A

True

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8
Q

Paracetamol is primarily absorbed in ________

A

small intestines (minimal in stomach)

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9
Q

Distribution of Paracetamol: 1 L/kg, protein binding at
____________ at therapeutic doses; __________ at toxic concentrations

A

10% to 25%; 8% to
43%

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10
Q

Half life Elimination of Paracetamol:
Neonates
Infants
Children
Adolosecents
Adults

A

7 hrs, 4 hrs, 3 hrs, 3 hrs, 2 hrs

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11
Q

Paracetamol is excreted via

A

Renal (urine)

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12
Q

60-80% of Paracetamol is excreted as

A

glucuronide metabolites

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13
Q

20-30% of Paracetamol is excreted as

A

sulfate metabolites

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14
Q

about 8% of Paracetamol is excreted as

A

cysteine and mercapturic acid metabolites

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15
Q

Onset ofAction:

Oral:
IV for Analgesia
IV for antipyresis

A

less than an hour; 5-10 minutes; within 30 minutes

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16
Q

Duraiton of Action

Oral and IV for Analgesia
IV for Antipyresis

A

4 to 6 hours; More than 6 hours

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17
Q

CYP Enzymes involved in metabolism

A

CYP2E1, 1A2, 2A6, and 3A4

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18
Q

has an extremely short half-life and is rapidly conjugated with
glutathione

A

N-acetyl-p-benzoquinoneimine (NAPQI)

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19
Q

NAPQI is _______ excreted

A

renally

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20
Q

In excess formation or with glutathione reduction, it covalently
binds to the cysteinyl sulfhydryl groups of hepatocellular proteins

A

NAPQI

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21
Q

causes an ensuing cascade of oxidative
damage and mitochondrial dysfunction

A

NAPQI-protein adducts

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22
Q

subsequent inflammatory response
propagates hepatocellular injury and
death

A

NAPQI-protein adducts

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23
Q

Necrosis primarily occurs in the
centrilobular (zone III) region, owing to
the greater production of NAPQI by
these cells

A

NAPQI-protein adducts

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24
Q

Maximum daily dose of Paracetamol for children (general)

A

75 mg/kg BW

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25
Q

Maximum daily dose of Paracetamol for children (younger than 12 years and/or less than 50 kg)

A

10-15 mg/kg every 4-6 hours. No more than 5 doses per 24-hour period

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26
Q

Maximum daily dose of Paracetamol for adults

A

4 g given
325 – 650 mg every 4– 6 hours or 1 g every 6 hours

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27
Q

Minimum hepatotoxic dose as a single acute ingestion
Children:
Adult:

A

Children: 150-200 mg/kg BW
Adult: 7.5-10 g

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28
Q

Phase: 30 minutes to 24 hours after ingestion

A

Phase 1: PreclinicalToxic Effects

29
Q

Patients may be asymptomatic or report anorexia, nausea or
vomiting, and malaise

A

Phase 1: PreclinicalToxic Effects

30
Q

Liver function tests may remain within normal limits

A

Phase 1: PreclinicalToxic Effects

31
Q

If with elevated paracetamol concentration, metabolic acidosis
which may lead to comatose state

A

Phase 1: PreclinicalToxic Effects

32
Q

24 to 48 hours after ingestion

A

Phase 2: Hepatic Injury

33
Q

Elevation of transaminases levels

A

Phase 2: Hepatic Injury

34
Q

Elevated PT, INR and bilirubin

A

Phase 2: Hepatic Injury

35
Q

Right upper quadrant tenderness may be present

A

Phase 2: Hepatic Injury

36
Q

Some patients may report decreased urinary output (oliguria)

A

Phase 2: Hepatic Injury

37
Q

Tachycardia and hypotension indicate ongoing volume losses

A

Phase 2: Hepatic Injury

38
Q

Moderate elevations in hepatic transaminases

A

Phase 3: Hepatic Failure

39
Q

Hepatic necrosis and dysfunction associated with jaundice,
coagulopathy, hypoglycemia, and hepatic encephalopathy

A

Phase 3: Hepatic Failure

40
Q

May have continued nausea and vomiting, abdominal pain, and a
tender hepatic edge

A

Phase 3: Hepatic Failure

41
Q

Acute renal failure in some critically ill patients

A

Phase 3: Hepatic Failure

42
Q

Death from multiple organ failure

A

Phase 3: Hepatic Failure

43
Q

72 to 96 hours after ingestion

A

Phase 3: Hepatic Failure

44
Q

4 days to 3 weeks after ingestion

A

Phase 4: Recovery Phase

45
Q

History taking in Paracetamol toxicity

A

numbers of tablets taken
time it was taken
dosage form
whether it was taken at the same time
taken with alcohol
suicide risk

46
Q

Nomogram tracking begins ________ hours after ingestion and ends _________
hours after ingestion

A

4; 24

47
Q

serum studies (in patients with abdominal pain)

A

Lipase and amylase

48
Q

serum studies (in females, childbearing age)

A

Serum human chorionic gonadotropin

49
Q

serum studies (in patients with concern of co-ingestants)

A

Salicylate level

50
Q

serum studies (in clinically compromised patients

A

Arterial blood gas and ammonia

51
Q

serum studies (to check for hematuria and proteinuria)

A

urinalysis

52
Q

to detect additional clues for co-ingestants

A

ECG

53
Q

in patients with altered mental status

A

CT scan

54
Q

Approximately 12 hours after an acute ingestion, liver
enzymes show a subclinical rise in serum transaminase levels

A

Phase 1:

55
Q

Elevated ALT and AST levels, PT, and bilirubin values; renal
function abnormalities may be present and indicate nephrotoxicity

A

Phase 2:

56
Q

: Severe hepatotoxicity as evident on serum concentrations,
hepatic necrosis to be confirmed by liver biopsy.

A

Phase 3:

57
Q

It is given within 8 hours after an acute
paracetamol ingestion

A

N -acetylcysteine (NAC)

58
Q

Can also be beneficial in patients who
present more than 24 hours after ingestion

A

N -acetylcysteine (NAC)

59
Q

T/F: N -acetylcysteine (NAC) is approved for both oral and IV administration

A

True

60
Q

The FDA-approved regimen for oral NAC is as follows:
* Loading dose of ________ mg/kg BW
* 17 doses of _________ BW given every 4 hours
* Total treatment duration of _______ hours
* Total amount dose of NAC delivered: __________ mg/kg BW

A

140 ;70 mg/kg ; 72; 1330

61
Q

T/F: IV NAC is preferred in Potential fetal paracetamol toxicity in a pregnant woman

A

true

62
Q

For IV NAC:
* Loading dose: __________ mg/kg BW IV; mix in 200 mL of 5% dextrose in
water (D5W) and infuse over 1 h
* Dose 2: __________ mg/kg BW IV in 500 mL D5W over 4 h
* Dose 3: __________ mg/kg BW IV in 1000 mL D5W over 16 h

A

150; 50; 100

63
Q

Total treatment duration of IV Nac and total NAC delivered

A

21 hours; 300 mg/kg

64
Q

IV NAC In patients who weigh more than 100 kg

A

Loading dose: 15,000 mg infused IV over 1 hour
* First maintenance dose: 5,000 mg IV over 4 hours
* Second maintenance dose: 10,000 mg over 16 hours

65
Q

Intermittent IV NAC infusion considered for late-presenting or chronic
ingestion:

Loading dose: __________ mg/kg BW IV, diluted in 500 mL D5W and
infused over __________ hour
* Maintenance doses: ___________ mg/kg BW IV are given every ________ hours for at
least 12 doses, dilute each dose in 250 mL of D5W and infuse over
a minimum of 1 hour

A

140; 1
70;4

66
Q

Activated charcoal for adult

A

50g

67
Q

Activated charcoal dose for children

A

1 g/kg BW up to 50 g

68
Q

Criteria for liver
transplantation include the
following:

A
  • Metabolic acidosis
  • Renal failure
  • Coagulopathy
  • Encephalopathy

Toxi Lab (6 decks)

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