Paracetamol

Question 1

(Year) First clinical use
by von Mering

Answer 1

1893

Question 2

(Year) Extensive
medical use as
prescription drug

Answer 2

1947

Question 3

(Year) Commercial
availability in US

Answer 3

1950

Question 4

(Year) Became OTC

Answer 4

1960

Question 5

(year) Discovery of
hepatotoxicity
as ADR

Answer 5

1966

Question 6

(Year) Became mainstay
analgesic and
antipyretic

Answer 6

1980s

Question 7

T/F: Paracetamol has no inflammatory property

Answer 7

True

Question 8

Paracetamol is primarily absorbed in ________

Answer 8

small intestines (minimal in stomach)

Question 9

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

Answer 9

10% to 25%; 8% to
43%

Question 10

Half life Elimination of Paracetamol:
Neonates
Infants
Children
Adolosecents
Adults

Answer 10

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

Question 11

Paracetamol is excreted via

Answer 11

Renal (urine)

Question 12

60-80% of Paracetamol is excreted as

Answer 12

glucuronide metabolites

Question 13

20-30% of Paracetamol is excreted as

Answer 13

sulfate metabolites

Question 14

about 8% of Paracetamol is excreted as

Answer 14

cysteine and mercapturic acid metabolites

Question 15

Onset ofAction:

Oral:
IV for Analgesia
IV for antipyresis

Answer 15

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

Question 16

Duraiton of Action

Oral and IV for Analgesia
IV for Antipyresis

Answer 16

4 to 6 hours; More than 6 hours

Question 17

CYP Enzymes involved in metabolism

Answer 17

CYP2E1, 1A2, 2A6, and 3A4

Question 18

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

Answer 18

N-acetyl-p-benzoquinoneimine (NAPQI)

Question 19

NAPQI is _______ excreted

Answer 19

renally

Question 20

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

Answer 20

NAPQI

Question 21

causes an ensuing cascade of oxidative
damage and mitochondrial dysfunction

Answer 21

NAPQI-protein adducts

Question 22

subsequent inflammatory response
propagates hepatocellular injury and
death

Answer 22

NAPQI-protein adducts

Question 23

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

Answer 23

NAPQI-protein adducts

Question 24

Maximum daily dose of Paracetamol for children (general)

Answer 24

75 mg/kg BW

Question 25

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

Answer 25

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

Question 26

Maximum daily dose of Paracetamol for adults

Answer 26

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

Question 27

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

Answer 27

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

Question 28

Phase: 30 minutes to 24 hours after ingestion

Answer 28

Phase 1: PreclinicalToxic Effects

Question 29

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

Answer 29

Phase 1: PreclinicalToxic Effects

Question 30

Liver function tests may remain within normal limits

Answer 30

Phase 1: PreclinicalToxic Effects

Question 31

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

Answer 31

Phase 1: PreclinicalToxic Effects

Question 32

24 to 48 hours after ingestion

Answer 32

Phase 2: Hepatic Injury

Question 33

Elevation of transaminases levels

Answer 33

Phase 2: Hepatic Injury

Question 34

Elevated PT, INR and bilirubin

Answer 34

Phase 2: Hepatic Injury

Question 35

Right upper quadrant tenderness may be present

Answer 35

Phase 2: Hepatic Injury

Question 36

Some patients may report decreased urinary output (oliguria)

Answer 36

Phase 2: Hepatic Injury

Question 37

Tachycardia and hypotension indicate ongoing volume losses

Answer 37

Phase 2: Hepatic Injury

Question 38

Moderate elevations in hepatic transaminases

Answer 38

Phase 3: Hepatic Failure

Question 39

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

Answer 39

Phase 3: Hepatic Failure

Question 40

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

Answer 40

Phase 3: Hepatic Failure

Question 41

Acute renal failure in some critically ill patients

Answer 41

Phase 3: Hepatic Failure

Question 42

Death from multiple organ failure

Answer 42

Phase 3: Hepatic Failure

Question 43

72 to 96 hours after ingestion

Answer 43

Phase 3: Hepatic Failure

Question 44

4 days to 3 weeks after ingestion

Answer 44

Phase 4: Recovery Phase

Question 45

History taking in Paracetamol toxicity

Answer 45

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

Question 46

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

Answer 46

4; 24

Question 47

serum studies (in patients with abdominal pain)

Answer 47

Lipase and amylase

Question 48

serum studies (in females, childbearing age)

Answer 48

Serum human chorionic gonadotropin

Question 49

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

Answer 49

Salicylate level

Question 50

serum studies (in clinically compromised patients

Answer 50

Arterial blood gas and ammonia

Question 51

serum studies (to check for hematuria and proteinuria)

Answer 51

urinalysis

Question 52

to detect additional clues for co-ingestants

Answer 52

ECG

Question 53

in patients with altered mental status

Answer 53

CT scan

Question 54

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

Answer 54

Phase 1:

Question 55

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

Answer 55

Phase 2:

Question 56

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

Answer 56

Phase 3:

Question 57

It is given within 8 hours after an acute paracetamol ingestion

Answer 57

N -acetylcysteine (NAC)

Question 58

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

Answer 58

N -acetylcysteine (NAC)

Question 59

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

Answer 59

True

Question 60

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

Answer 60

140 ;70 mg/kg ; 72; 1330

Question 61

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

Answer 61

true

Question 62

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

Answer 62

150; 50; 100

Question 63

Total treatment duration of IV Nac and total NAC delivered

Answer 63

21 hours; 300 mg/kg

Question 64

IV NAC In patients who weigh more than 100 kg

Answer 64

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

Question 65

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

Answer 65

140; 1 70;4

Question 66

Activated charcoal for adult

Answer 66

50g

Question 67

Activated charcoal dose for children

Answer 67

1 g/kg BW up to 50 g

Question 68

Criteria for liver transplantation include the following:

Answer 68

* Metabolic acidosis * Renal failure * Coagulopathy * Encephalopathy