Paracetamol

- Action is similar to NSAIDs

- Weaker analgesic than NSAIDs or other COX-2 selective inhibitors
- Preferred due to better tolerance compared to NSAIDs

Mode of Action
1. Inhibits COX-1 and COX-2 isoenzymes thru metabolism
- COX officially known as prostaglandin-endoperoxide synthase (PTGS), is a family of enzymes
responsible for formation of prostanoids, including thromboxane and prostaglandins such as
prostacyclin, from arachidonic acid
- Prostanoids are a subclass of eicosanoids consisting of the prostaglandins (mediators of
inflammatory and anaphylactic reactions), the thromboxanes (mediators of vasoconstriction),
and the prostacyclins (active in the resolution phase of inflammation)
- Prostaglandins are one of the more significant ones in contributing to inflammatory process
- Isoenzymes are enzymes that differ in amino acid sequence but catalyze the same chemical
reaction
2. This results in inhibition of phenoxyl radical formation from a critical tyrosine amino acid
residue which is essential for the activity of COX-1 and COX-2 prostaglandin synthesis
3. Paracetamol shows selectivity for inhibition of synthesis of prostaglandins in low levels of
arachidonic acid and peroxides. Conversely, it has little activity at substantial levels of
arachidonic acid and peroxides
- Thus, paracetamol does not suppress severe inflammation of rheumatoid arthritis and acute
gout but does inhibit lesser inflammation resulting from extraction of teeth and is also active in
a variety of inflammatory tests in experimental animals
4. Paracetamol also often appears to have COX-2 selectivity
- Shown by poor anti-platelet activity and good gastrointestinal tolerance (because of this
perhaps not all prostaglandins are targeted)
- A type of prostaglandin called thromboxane stimulates constriction and clotting of platelets
5. Unlike both non-selective NSAIDs and selective COX-2 inhibitors, paracetamol inhibits other
peroxidase enzymes including myeloperoxidase
- Inhibition of myeloperoxidase involves paracetamol oxidation and decreased formation of
halogenating oxidants
- Halogenating oxidants may be associated with multiple inflammatory pathologies (e.g.
atherosclerosis and rheumatic diseases)
- Paracetamol may, therefore, slow development of these diseases
6. Paracetamol, NSAIDs, and selective COX-2 inhibitors have reduced effect due to inhibitors
from many endogenous neurotransmitter systems including serotonergic, opioid and
cannabinoid systems

Source: https://www.ncbi.nlm.nih.gov/pubmed/23719833