Acetaminophen is a popular over-the-counter analgesic and antipyretic that is found in many medications. It works by weakly inhibiting COX-1 and COX-2 enzymes and activating cannabinoid and vanilloid receptors in the central nervous system. It has a rapid oral absorption and is metabolized in the liver. While usually safe in recommended doses, larger doses can cause liver toxicity through a reactive metabolite. Its indications include mild to moderate pain and fever, and it is dosed differently for various patient populations, with maximum daily doses depending on age and weight.

1. ACETAMINOPHEN
MONGERA MWAMBA

2. ▪ Tylenol/paracetamol
▪ Popular analgesic and antipyretic found in many OTC and
prescription drugs
▪ Active metabolite of phenacetin and the only p-aminophenol
available in clinical practice
▪ weak COX-1 and COX-2 inhibitor in peripheral tissues with no
significant anti-inflammatory
▪ In recommended doses it is safe with remarkably few s/e

3. Mechanism of Action
▪ In the brain and spinal cord, acetaminophen is conjugated with
arachidonic acid to form N – arachidonoylphenolamine (AM404)
▪ AM404 activates the capsaicin receptor (TRPV1) and the
cannabinoid CB1 receptor systems, both of which confer
analgesia in the central nervous system.
▪ Inhibition of prostaglandin production in the brain produces
antipyretic effect.

4. Pharmacokinetics
▪ Routes of administration
a) Oral
- Rapidly absorbed from small intestine
- peak plasma concentration in 30 – 60 mins
- oral bioavailability is 63-89%
- Half life : 1.25 – 3 h(adolescents); 2 – 5 h (children) ; 4h (infants)
and 2 – 3 h (adults) – unaffected by renal function

5. b) Rectal administration
- absorption is unpredictable
- bioavailability 24 – 98 %
- Mean plasma therapeautic ranges achieved in 1- 2 hours
- Suppository formlation (lipophilic/hydrophilic), volume of the
suppository, number of suppositories used, particle size of the
paracetamol and rectal pH affect absorption and bioavailability.

6. c) Intravenous administration
- 10mg.ml-1 aqueous solution in 50ml and 100ml glass bottles to be
infused in 15 mins
- Onset of action : 15 – 30 mins
- Average serum therapeautic range achieved in 20 mins
- Half life : 2.4h(adolescents); 2 – 3 h(adults); 2 – 5 h(children) ; 4 –
10h (neonates) – unaffected by renal function.
▪ Poorly protein bound 10 – 20%
▪ Metabolized by hepatic microsomal enzymes to inactive glucoronide,
sulphate and cystein

7. ▪ larger doses (>4mg/kg/d) , a highly reactive ad hepatotoxic
metabolite N-acetyl-p-benzoquinone imine. It leads to liver failure
by depleting the liver’s natural antioxidant glutathione and
directly damaging liver cells.
▪ Antidote : acetylcysteine acts as precursor for glutathione and
directly neutralizes N-acetyl-p-benzoquinone imine
Pharmacodynamics
▪ Reduces postoperative opioid requirement by 30%
▪ Effective antipyretic

8. Indications
▪ mild to moderate pain e.g headache, myalgia, postpartum pain
▪ Fever
Contraindications
▪ paracetamol hypersensitivity
▪ severe hepatocellular insufficiency

9. Adverse effects
▪ In therapeutic doses – mild reversible increase in hepatic
enzymes may occur
▪ larger doses – dizziness , excitement, and disorientation
▪ Ingestion of 15 g – fatal : death being caused by severe
hepatotoxicity with centrilobular necrosis, sometimes associated
with acute renal tubular necrosis

10. ACETAMINOPHEN POSOLOGY
Regular strength: (PO/PR)
▪ Adults : 325 – 650 mg every 4- 6 h ,max dose 4g/24hrs
Extra strength : PO
▪ 1000 mg , 6 – 8 hourly , max 4g/24hrs
▪ Onset : 10 – 60 mins, duration : 3 – 4 h

11. Pediatric Oral Acetaminophen
▪ Neonates 28 – 31 weeks gestation
- LD 20mg/kg
- 10 – 15 mg/kg/dose q12h PRN ,max 40mg/kg/d
▪ Neonates 32 -37 weeks gestation
- LD 20mg/kg
- 10 – 15 mg/kg/dose, max dose 60mg/kg/d
▪ Neonates 10 – 29 days
- LD 20mg/kg
- 10 – 15mg/kg/dose ,max 90mg/kg/d
▪ Children and adolescents :
- <60kgs : 10 – 15mg/kg/dose , max 15mg/kg/dose or 1g/dose
whichever is less or
- 75mg/kg/d or < 4000mg/d whichever is less

12. Intravenous
▪ Neonates : 12.5mg/kg q6h max dose 50mg/kg/d
▪ Infants : 29 days – 2 years : 15mg/kg q6h max dose 60mg/kg/d
▪ 2 – 12 years : 12.5mg/kg q4h or 15mg/kg q6h max 75mg/kg/d
▪ < 15kgs :12.5mg/kg q4h or 15mg/kg q6h max 750mg/dose or 3.5g/d
▪ ≥ 50kgs : 650mg q4h or 1000mg q6h max dose 4g/d
ACETAMINOPHEN ANTIDOTE
▪ Methionine : effective protection up to 10 – 12 h post ingestion
▪ Acetylcysteine : effective within 24h post ingestion.

13. REFFERENCES:
1. Morgan and Mikhail’s .2018. Clinical anesthesiology. 6th Edition. McGraw Hill
education . New York. USA
2. Dr. Paul Clyburn, Dr.Rachel Collis and Dr. Sarah Harries .2010 .Obstetric
Anesthesia for Developing Countries . 1st Edition.
3. Manuel C. Padro Jr. and Ronald Miller. .2018. Basics of Anesthesia Seventh
Edition .
4. Chris Oscier, Nicki Bosley and Quentin Milner. 2007. Paracetamol - A Review of
Three Routes of Administration. Updates in Anesthesia . Vol 23 ,p 111 – 114.
5. Robert K. Stoelting, MD. 2015. STOELTING ’S HANDBOOK OF Pharmacology
and Physiology in Anesthetic Practice. Third Edition. Wolters Kluwer Health.
Pune – Maharashtra ,India .
6. Alan R. Aitkenhead. 2007. Smith and Aitkenhead’s Textbook of Anaesthesia.
6th Edition. Churchill Livingstone – Elsevier . China .