Discuss the mechanism of action of Tylenol. How does it work? What biological pathways are involved?
Mechanism and mode of action:
Tylenol (acetaminophen) is a non-opioid analgesic. It belongs to
the class of pain killers like aspirin, ibuprofen and naproxen.
Non-opioid analgesics work by inhibiting an enzyme, prostaglandin H
synthase (PGHS), currently known as cyclooxygenase (COX).
COX is a catalyst for the conversion of a fatty acid, arachidonic acid (contained in cell walls) abbreviated as AA into prostaglandins (PGH2). Prostaglandins serve a number of protective functions in the body, they cause pain and inflammation after cell injury by a number of mechanisms. By blocking COX, prostaglandins are produced in the central and peripheral nervous systems, thereby reduce both fever and inflammation.
Acetaminophen unlike other non-opioids reduce pain primarily in the central nervous system by more than one mechanism, possibly in part by inhibiting a form of COX known as COX-3. Therefore, acetoaminophen is suitable for headaches, fever and minor aches and pains, but won’t reduce inflammation due to, say, a muscle sprain.
Biological pathways:
PGHS is a bifunctional enzyme which possesses two
different enzymatic activities: cyclooxygenase and peroxidase
(POX).
The conversion of AA→PGH2 involves two reactions:
1. cyclization of AA to unstable 15-hydroxyperoxide (PGG2) with
the involvement of a cyclooxygenase component
2. double oxidation in position 9 and 11
Due to peroxidase activity of PGHS (POX), reduction of PGG2
molecule to its 15-
hydroxy analogue, unstable structure of PGH2 takes place.
Prostaglandin H2 (PGH2) is a substrate for specific synthases,
tissue-dependent isomerases. This catalyses the conversions into
different endogenous regulators such as D (PGD2), E (PGE2), F
(PGF2) series and prostacyclin (PGI2; prostacyclin is not a
prostaglandin and thromboxanes (TXA2 and TXB2). They all are
characterized by different biological activity
Conversion AA→PGH2, and also the formation of the aforementioned
regulators, have some favorable (anti-inflammatory, analgesic and
antipyretic).
Discuss the mechanism of action of Tylenol. How does it work? What biological pathways are involved?
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