June 4, 2023

This animated video briefly illustrate the four suggested pathways which might mediate the mechanisms of actions of Paracetamol (Acetaminophen)

Paracetamol or acetaminophen mechanism of action before going into the mechanism of action of paracetamol we need to answer this question why do we have two different names across the atlantic paracetamol and acetaminophen to answer this question we must go to the chemical name of this amazing drug which is para acetyl aminophenol complicated name yeah actually

Uk has followed the international non-proprietary name system which is coordinated by the world health organization the who the who chose 11 letters from this long name to constitute the internationally accepted generic name paracetamol however usa followed by canada and japan chose different 13 letters to build their own generic name which is acetaminophen and

We ended up with two different scientific names for the same drug and that’s weird now let’s go to the oldest drama in the pharmacological history which is the mechanism of action of paracetamol more than 60 years of using paracetamol as an analgesic and still we don’t know exactly how does it work frustrating isn’t it you’re right jackie but indeed we have some

Suggested mechanisms the mechanism of action of paracetamol is mediated through which of the following systems is it a serotonergic system b ecosynod system c cannabinoid system or d opioid system remember you still have four lifelines and the correct answer is indeed all of them are correct it is widely accepted that the analgesic effect of paracetamol is

Mediated through the cns but the central effect that is largely responsible for mediating paracetamol analgesic effect is still unclear actually the most widely accepted theory is that the activation of the serotonin pathway in the cns largely mediates the analgesic effect of paracetamol however other pathways such as ecosonic cannabinoid opioid and nitric oxide

Could participate in mediating the pharmacological effects of paracetamol surely we will start with the most widely accepted mechanism which is the serotonin pathway now we illustrate the serotonin inhibitory pathways with and without paracetamol in general the painful stimuli in peripheral tissues are transported by nociceptor nerves toward the dorsal horn of the

Spinal cord and from there they ascend toward pain processing centers in the brain naturally we have opposite descending inhibitory pathways which interfere with the ascending pain signaling at the level of the dortal horn therefore decreasing the pain sensation filed by peripheral tissue injury among various transmitters serotonins play important roles in these

Descending inhibitory pathways it has been found that paracetamol enhances the inhibitory effects of serotonin descending pathways to suppress the pain sensation elicited by the tissue damage actually different research groups have supported the hypothesis that paracetamol enhances the inhibitory effects of the serotonergic pathways now let’s go back to the other

Suggested mechanisms of paracetamol action and this time we will go through the ecosynoid system ecosonoids production pathways start from the cell membrane phospholipid which is degraded by phospholipase a2 enzymes to produce arachidonic acid arachidonic acid is metabolized by famous family of isoenzymes known as cyclooxygenase which is abbreviated as cox there

Are two well-known isoenzymes of this family cox-1 and cox-2 the prostaglandin g2 produced by cox enzymes is an intermediate transient compound which is rapidly reduced by peroxidase enzyme to produce prostaglandin h2 the prostaglandin h2 is the direct precursor of prostacyclin thromboxane and all other prostaglandins such as prostaglandin d2 e2 and f2 alpha

These prostaglandins are actively involved in mediated pain fever and inflammation non-steroidal anti-inflammatory drugs group abbreviated as nsaids is a well-known drug family that includes aspirin and ibuprofen nsaids inhibit both cox-1 and cox-2 enzymes and because paracetamol and nsaids have similar antipyretic and analgesic effects it has been suggested

That paracetamol exerts its analgesic and antipyretic effects through inhibition of cyclooxygenase enzymes if paracetamol inhibits cox enzymes as you said white has no anti-inflammatory effects like nsaids like nsaids paracetamol has analgesic and antipyritic effects but unlike insate it has no anti-inflammatory effects but why this utterly depressing question

That had irritated scientists for decades until finally they have approached the answer it has been discovered that paracetamol inhibits mainly peroxidase enzyme rather than cyclooxygenase enzyme peroxidase enzymes are present in low concentrations in the cns therefore paracetamol can effectively inhibit it however during inflammation in peripheral tissues the

Destructed cells produce large amounts of peroxidase enzymes that can’t be inhibited by paracetamol therefore paracetamol has no anti-inflammatory effects that makes sense now now we will go to the third suggested pathway of paracetamol action which is cannabinoid’s pathway this strange story started from the metabolism of paracetamol in the liver to produce

The intermediate metabolites p aminophenol which travels to the brain where it is conjugated there with arachidonic acid derived from the cell membranes to produce am 404 molecules this conjugation reaction is catalyzed by fatty acid amide hydrolase enzyme this am404 activates endogenous cannabinoid receptors mediates the release of endogenous cannabinoids

And mediates antibiotic effects through inhibition of central prostaglandin production all these biological effects of am404 supported the hypothesis that cannabinoids pathway might mediate the paracetamol effects interactions between paracetamol and endogenous cannabinoids could explain the feelings of relaxation and euphoria experienced by many people taking

Paracetamol away from its analgesic effect of course and now we reach to the last pathway in our delighted lecture which is the opioids pathway it has been suggested that the paracetamol effects could be partially mediated by opioid system some findings have contributed to this hypothesis paracetamol could partially work through activation of mu and kappa opioid

Receptors synergism between opioids and serotonergic pathways might mediate paracetamol effects am405 the paracetamol metabolite activates both opioid and cannabinoid receptors and that’s it i hope you find it helpful best wishes dr jihad hammad this video was narrated by dr haya al-shaykh you

Transcribed from video
Paracetamol (Acetaminophen): Mechanism of Action By Pharmacology Animation