HISTORY

1877- Harmon Morse synthesised paracetamol

at Johns Hopkins University 

1886- A. Cahn and P. Hepp introduced Acetanilide

in medical practice as Antifebrin

1887- clinical pharmacologist Joseph von Mering

tried paracetamol on humans

1893- von Mering published a paper reporting on

the clinical results of paracetamol with phenacetin

1899- Phenacetin was introduced into medicine by

Heinrich Dreser
HISTORY
1950- first marketed in the United States under
the name Triagesic (paracetamol + aspirin +
caffeine)

1953- marketed by Sterling-Winthrop Co. as

Panadol available only by prescription

1955- marketed as Children’s Tylenol Elixir

by McNeil Labratories

1959- became available without a prescription 

PARACETAMOL/ACETAMINOPHEN
• 2011- an IV formulation was approved in the U.S. for
inpatient adults and children aged >2 years
• available in more than 200 OTC and prescription medications
under different brand or trade names
• available in a variety of forms, such as elixirs, suspensions,
tablets (dissolvable and chewable), caplets, capsules, and
paraffin-base rectal suppositories
PARACETAMOL POISONING
• Acetaminophen Poisoning
• Most commonly used oral
analgesic and antipyretic
• Minimum toxic doses of
acetaminophen for a single
ingestion
Adults: 7.5-10 g
Children: 150 mg/kg; 200
mg/kg in healthy children
aged 1-6 years
• Overdose can occur at any age;
commonly in children
• 2009- FDA required that information
regarding the risk of acetaminophen-
induced hepatotoxicity be provided
with nonprescription and prescription
APAP-containing medications
• 2014- FDA: combination prescription
pain relievers containing >325 mg of
acetaminophen per tablet, capsule,
or other dosage form no longer be
prescribed
 NAPQI (N-ACETYL-P-
BENZOQUINONE IMINE)
about 4% is
metabolized
by the
cytochrome
P450 into
NAPQI
Small amount
is excreted
unchanged in
the urine

• During xenobiotic metabolism,

acetaminophen produces a
toxic byproduct
• Produced in small amounts
• Inactivated by conjugation
with glutathione (GSH)
SIGNS
AND
SYMPTO
MS
DIAGNOSIS

• To identify a patient who may be at risk of hepatoxicity, determine

the:
1. time(s) of ingestion
2. quantity
3. formulation of acetaminophen ingested
 DIAGNOSIS
• Serum Acetaminophen Concentration
-After a single ingestion, N -acetylcysteine (NAC) therapy is
guided by the serum APAP concentration.
-An APAP level 4 hours post ingestion of greater than 150 mcg/mL
(>993 µmol/L) reflects possible toxicity.

<1500 - Low risk

1500-10,000 - Low to
moderate risk

>10,000 - High risk

 DIAGNOSIS
• Rumack-Matthew nomogram
- concentration of acetaminophen
(mcg/mL) in relation to time (hrs)
-assess hepatotoxicity after single, acute
ingestion
-Nomogram tracking begins 4 hours after
ingestion (time when acetaminophen
absorption is likely to be complete) and ends
24 hours after ingestion
-About 60% of patients with values above
the "probable" line develop hepatotoxicity
-not be used to evaluate long-term or
repeated ingestions.
 DIAGNOSIS
• Recommended serum studies:
1. Liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase
[AST]), bilirubin [total and fractionated], alkaline phosphatase)
2. Prothrombin time (PT) with international normalized ratio (INR)
3. Glucose
4. Renal function studies (electrolytes, BUN, creatinine)
5. Lipase and amylase (in patients with abdominal pain)
6. Serum human chorionic gonadotropin (hCG) (in females of childbearing age)
7. Salicylate level (in patients with concern of co-ingestants)
8. Arterial blood gas and ammonia (in clinically compromised patients)

• Additional recommended studies:

1. Urinalysis (to check for hematuria and proteinuria)
2. ECG (to detect additional clues for co-ingestants)
• https://www.uspharmacist.com/article/acetaminophen-intoxica
tion-a-criticalcare-emergency
• https://www.sciencedirect.com/topics/pharmacology-toxicolog
y-and-pharmaceutical-science/napqi
• https://www.ncbi.nlm.nih.gov/pubmed/4033631
• https://en.wikipedia.org/wiki/Paracetamol_poisoning
• https://emedicine.medscape.com/article/820200-overview