Paracetamol

Paracetamol indications

analgesic in acute and chronic mild pain

antipyrexic

Paracetamol MOA

The mechanism of action of paracetamol is not fully understood. In the central nervous system, it acts as a reducing co-substrate of cyclooxygenase 2 (COX-2), reducing the availability of oxidized COX-2 needed for prostaglandin synthesis.

This interferes with pain signal transmission, reducing pain sensitivity, and lowers prostaglandin E2 (PGE2) concentrations in the hypothalamus, reducing fever.

Paracetamol has minimal anti-inflammatory action in peripheral tissues, possibly due to inhibition by peroxides, which are low in the central nervous system but high in inflamed tissue.

Other actions of paracetamol and its metabolites, such as activating descending serotonergic pathways and inhibiting neuronal reuptake of endogenous cannabinoids, may also contribute to its therapeutic effect.

Paracetamol adverse effects

very safe with very few side effects.

in overdose paracetamol causes liver failure. metabolised by cytochrome P450 (CYP) enzymes to a toxic metabolite (N-acetyl-p-benzoquinone imine (NAPQI)), which is conjugated with glutathione before elimination.

In overdose, this elimination pathway is saturated, and NAPQI accumulation causes liver damage.

treat with acetylcysteine.

Paracetamol warnings and interactions

dose reduced in those at risk of liver toxicity: chronic excessive alcohol use, malnutrition, low body weigh <50kg or liver impairment

cyp inducers (phenytoin, carbamazepine) may also increase risk of liver damage

Paracetamol practical prescribing

on GSL max dose 4g a day. 1g every 4-6 hours. always state max dose on prescription

IV paracetamol solution may be infused over 15 minutes or diluted in 0.9% sodium chloride or 5% glucose solution before administration, depending on the product.

effect usually after 30 minutes, many medicines from chemist contain paracetamol , always check and also not exceed max dose

use pain scores and stop when pain subside

In paracetamol overdose, blood tests including international normalised ratio (INR), serum alanine aminotransferase, and creatinine concentration should be measured to detect liver and renal injury