Paracetamol Flashcards
(Year) First clinical use
by von Mering
1893
(Year) Extensive
medical use as
prescription drug
1947
(Year) Commercial
availability in US
1950
(Year) Became OTC
1960
(year) Discovery of
hepatotoxicity
as ADR
1966
(Year) Became mainstay
analgesic and
antipyretic
1980s
T/F: Paracetamol has no inflammatory property
True
Paracetamol is primarily absorbed in ________
small intestines (minimal in stomach)
Distribution of Paracetamol: 1 L/kg, protein binding at
____________ at therapeutic doses; __________ at toxic concentrations
10% to 25%; 8% to
43%
Half life Elimination of Paracetamol:
Neonates
Infants
Children
Adolosecents
Adults
7 hrs, 4 hrs, 3 hrs, 3 hrs, 2 hrs
Paracetamol is excreted via
Renal (urine)
60-80% of Paracetamol is excreted as
glucuronide metabolites
20-30% of Paracetamol is excreted as
sulfate metabolites
about 8% of Paracetamol is excreted as
cysteine and mercapturic acid metabolites
Onset ofAction:
Oral:
IV for Analgesia
IV for antipyresis
less than an hour; 5-10 minutes; within 30 minutes
Duraiton of Action
Oral and IV for Analgesia
IV for Antipyresis
4 to 6 hours; More than 6 hours
CYP Enzymes involved in metabolism
CYP2E1, 1A2, 2A6, and 3A4
has an extremely short half-life and is rapidly conjugated with
glutathione
N-acetyl-p-benzoquinoneimine (NAPQI)
NAPQI is _______ excreted
renally
In excess formation or with glutathione reduction, it covalently
binds to the cysteinyl sulfhydryl groups of hepatocellular proteins
NAPQI
causes an ensuing cascade of oxidative
damage and mitochondrial dysfunction
NAPQI-protein adducts
subsequent inflammatory response
propagates hepatocellular injury and
death
NAPQI-protein adducts
Necrosis primarily occurs in the
centrilobular (zone III) region, owing to
the greater production of NAPQI by
these cells
NAPQI-protein adducts
Maximum daily dose of Paracetamol for children (general)
75 mg/kg BW
Maximum daily dose of Paracetamol for children (younger than 12 years and/or less than 50 kg)
10-15 mg/kg every 4-6 hours. No more than 5 doses per 24-hour period
Maximum daily dose of Paracetamol for adults
4 g given
325 – 650 mg every 4– 6 hours or 1 g every 6 hours
Minimum hepatotoxic dose as a single acute ingestion
Children:
Adult:
Children: 150-200 mg/kg BW
Adult: 7.5-10 g
Phase: 30 minutes to 24 hours after ingestion
Phase 1: PreclinicalToxic Effects
Patients may be asymptomatic or report anorexia, nausea or
vomiting, and malaise
Phase 1: PreclinicalToxic Effects
Liver function tests may remain within normal limits
Phase 1: PreclinicalToxic Effects
If with elevated paracetamol concentration, metabolic acidosis
which may lead to comatose state
Phase 1: PreclinicalToxic Effects
24 to 48 hours after ingestion
Phase 2: Hepatic Injury
Elevation of transaminases levels
Phase 2: Hepatic Injury
Elevated PT, INR and bilirubin
Phase 2: Hepatic Injury
Right upper quadrant tenderness may be present
Phase 2: Hepatic Injury
Some patients may report decreased urinary output (oliguria)
Phase 2: Hepatic Injury
Tachycardia and hypotension indicate ongoing volume losses
Phase 2: Hepatic Injury
Moderate elevations in hepatic transaminases
Phase 3: Hepatic Failure
Hepatic necrosis and dysfunction associated with jaundice,
coagulopathy, hypoglycemia, and hepatic encephalopathy
Phase 3: Hepatic Failure
May have continued nausea and vomiting, abdominal pain, and a
tender hepatic edge
Phase 3: Hepatic Failure
Acute renal failure in some critically ill patients
Phase 3: Hepatic Failure
Death from multiple organ failure
Phase 3: Hepatic Failure
72 to 96 hours after ingestion
Phase 3: Hepatic Failure
4 days to 3 weeks after ingestion
Phase 4: Recovery Phase
History taking in Paracetamol toxicity
numbers of tablets taken
time it was taken
dosage form
whether it was taken at the same time
taken with alcohol
suicide risk
Nomogram tracking begins ________ hours after ingestion and ends _________
hours after ingestion
4; 24
serum studies (in patients with abdominal pain)
Lipase and amylase
serum studies (in females, childbearing age)
Serum human chorionic gonadotropin
serum studies (in patients with concern of co-ingestants)
Salicylate level
serum studies (in clinically compromised patients
Arterial blood gas and ammonia
serum studies (to check for hematuria and proteinuria)
urinalysis
to detect additional clues for co-ingestants
ECG
in patients with altered mental status
CT scan
Approximately 12 hours after an acute ingestion, liver
enzymes show a subclinical rise in serum transaminase levels
Phase 1:
Elevated ALT and AST levels, PT, and bilirubin values; renal
function abnormalities may be present and indicate nephrotoxicity
Phase 2:
: Severe hepatotoxicity as evident on serum concentrations,
hepatic necrosis to be confirmed by liver biopsy.
Phase 3:
It is given within 8 hours after an acute
paracetamol ingestion
N -acetylcysteine (NAC)
Can also be beneficial in patients who
present more than 24 hours after ingestion
N -acetylcysteine (NAC)
T/F: N -acetylcysteine (NAC) is approved for both oral and IV administration
True
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
140 ;70 mg/kg ; 72; 1330
T/F: IV NAC is preferred in Potential fetal paracetamol toxicity in a pregnant woman
true
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
150; 50; 100
Total treatment duration of IV Nac and total NAC delivered
21 hours; 300 mg/kg
IV NAC In patients who weigh more than 100 kg
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
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
140; 1
70;4
Activated charcoal for adult
50g
Activated charcoal dose for children
1 g/kg BW up to 50 g
Criteria for liver
transplantation include the
following:
- Metabolic acidosis
- Renal failure
- Coagulopathy
- Encephalopathy
