Acetaminophen (Paracetamol)
Author: Dr. Wamiq Ansari
Last Updated:
Classification
1. Class: Non-NSAID Analgesic and Antipyretic.
2. Sub-class: Para-amino phenol derivative.
Mechanism of Action
1. Analgesic Effect:
Inhibits COX-3 enzyme in brain causing decreased production of Prostglandins , leading to reduced transmission of pain signals.
2. Antipyretic Effect:
Acts directly on Heat-Reagulating areas of Hypothalamus;;
- Pre-Optic Area - stimulates thermosensitive neurons that detect body heat changes and regulate heat production and dissipation.
- Anterior Hypothalamaus - triggers vasodilation that leads to sweating. Thus causing heat loss and reduction in temperature.
Pharmacokinetics
1. Half Life: 2-3 hours (patients with no renal or hepatic disease).
2. Secretion: Milk.
3. Major Metabolism: in liver by conjugtion with Glutathione and other metabolites.
4. Minor Metabolism: by Cytochrome P450 System , forming N-Acetyl-P-Benzoquinone Imine , that acts as an intermediate toxic metabolite.
5. Excretion: mainly urine.
Indications
1. Fever.
2. Mild to Moderate Pain.
3. Post-Operative Pain
4. As an alternate for Intermediate Aspirin Dose
Contraindications
1. Severe Liver Parenchymal Disease
2. Severe Renal Impairement.
3. Known Hypersensitivity.
Dosage
Oral or Per Rectal
| Neonates | 10-15 mg/kg/dose x every 6-8 hour. |
| Infants and Children | 10-15 mg/kg/dose x every 4-6 hour. |
Parenteral
| Neonates | 12.5 mg/kg/dose x every 6 hour. |
| Infants and Children less than 2 years | 15 mg/kg/dose x every 6 hour. |
| Children 2 years or more | 15 mg/kg/dose x every 6 hour OR 12.5 mg/kg/dose x every 4 hourly. |
Maximum Dosage
Oral or Per Rectal
| All age group | 90 mg/kg/day OR 4000 mg/day. |
Parenteral
| Neonates | 50 mg/kg/day. |
| Infants and Children less than 2 years | 60 mg/kg/day. |
| Children 2 years or more | 75 mg/kg/day OR 3750 mg/day. |
Renal Adjustment Dosage
| eGFR 10-50 mL/min/1.73m² | 100% of the calculated dose can be given every 6 hour. |
| eGFR less than 10 mL/min/1.72m² or undergoing dialysis | 100% of the calculated dose can be given every 8 hour. |
Hepatic Adjustment Dosage
| Mild to Moderate Hepatic Impairment | Lesser than the usual dose (after senior consultation). |
| Severe Hepatic Impairment | Contraindicated. |
Adverse Effects
1. Gastrintestinal upset.
2. Hepatic Failure.
Toxicity
| Single, Acute Toxic Dose | 200 mg/kg. |
| Repeated Toxic Dose | more than 90mg/kg/day on consecutive days. |
Read more about Acetaminophen (Paracetamol) Poisoning.
References
1. Vanderah, Todd W. Basic and Clinical Pharmacology 16th Edition. McGraw Hill Professional, 3 Nov. 2023.
2. Tripathi, K D. Essentials of Medical Pharmacology. New Delhi, Jaypee Brothers Medical Publishers (P) Ltd, 2015
3. The, et al. The Harriet Lane Handbook, 23 Edition: South Asia Edition - E-Book. Elsevier Health Sciences, 20 June 2023.
4. Gerriets V, Anderson J, Patel P, et al. Acetaminophen. [Updated 2024 Jan 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan
5. Ohashi N, Kohno T. Analgesic Effect of Acetaminophen: A Review of Known and Novel Mechanisms of Action. Front Pharmacol. 2020 Nov 30;11:580289. doi: 10.3389/fphar.2020.580289. PMID: 33328986; PMCID: PMC7734311.