Pharmacology of Clopidogrel (Antiplatelet & Antithrombotic) by Dr Shikha Parmar
Hello students today we are going to study pharmacology of clopidogrel clopidogrel is an antiplatelet and thus antithrombotic drug it inhibits platelet aggregation and thereby it inhibits arterial thrombosis now one very important thing to note that platelets they are the main constituent of thrombus in arteries now in order to understand mechanism of action
Of propidogral let’s recapitulate physiology of platelet aggregation now this is a slide that explains physiology of platelet aggregation now in this slide i have shown here this is a tunica entema which is made up of endothelium that is endothelial cells uh these red color endothelial cells and platelets these are the blue colored platelets which are found
Circulating in the blood now uh prostacyclin that is pg i2 and nitric oxide these both are very strong inhibitors of platelet aggregation and they also prevent activation of platelets now these prostacyclin and nitric oxide they are synthesized by the endothelium and released in the blood now whenever there is damage to the endothelium now because of the damage
To the endothelium there is fall in the synthesis of prostacyclin there is fall in the synthesis of nitric oxide because of which the platelets they become activated and apart from this due to the damage to the endothelium the sub endothelial collagen is exposed so these are the blue colored fibers i have shown in the diagram this is the collagen now the damaged
Endothelial cells they release one will bring factor now this one will bring factor it binds to the collagen and further the activated platelets they bind to the one willim factor through the gp 1b receptors so these gp1b receptors they are found located on the surface of the platelets and the platelets they bind to one reliever in factor through these receptors
Now this have shown clearly in this diagram this is the diagram uh this is a collagen uh one bilibrane factor that is released by the damage endothelium and this is the activated platelet which binds to the ah one variant factor through gp1b receptor and this results in further activation of the activated platelets now these platelets they possess a receptor that
Is called as a gp2b3a receptor this receptor is also called as a fibrinogen receptor now activated platelet releases mediators of plated aggregation namely thromboxane a2 adp that is the adenosine diphosphate and 5-hydroxytryptamine that is 5ht or serotonin so these are the very strong or the very potent mediators of plated aggregation and these all really
These all are released by the activated platelet and further these mediators uh they activate gp2b3a receptors now these gp2b 3a receptors these are the fibrinogen receptors that means these receptors once activated they bind to the fibrinogen now fibrinogen further binds to the platelets so this uh diagram here we can see that this is the activated platelet
Uh there is activation of gp2b3a receptor which binds to fibrinogen fibrinogen further binds to another platelet again this gp2b 3a receptor it binds to the fibrinogen so there is formation of a platelet plug so all the platelets they form a platelet pluck there is cross-linking of platelets and a fibrinogen here it functions like a glue so there is a formation
Of the platelet plug which is very essential for the formation of clot and a clot that is formed inside a blood vessel is called as thrombus now this diagram now let’s understand this diagram this is a diagram of an activated platelet and let’s understand how the binding of adp to its receptor is responsible for the platelet aggregation now when the adp binds
To its p2 y12 receptors which are present on the surface of activated platelet adp stimulates g protein coupled receptors it stimulates g inhibitory proteins and it stimulates gq protein now let’s first understand what happens when there is uh stimulation of g inhibitory proteins now stimulation of g inhibitory uh proteins that is the g inhibitory receptors
Inhibit adenylyl cyclase and which reduces synthesis of cyclic amp in the platelets now reduced cyclic emp uh reduces the activation of protein kinase a now reduced protein kinase a causes reduced phosphorylation of vasp that is a vasodilator stimulated phosphoprotein so there is reduced uh phosphorylation of fast now one thing very important to understand that
It’s a vasp that stimulates the gp2b 3a receptors while phosphorylated vas is inactive so reduced phosphorylation reduced phosphorylation reduces phosphorylated vasc which is inactive but increases the level of active mass an increase in the level of active vas is responsible to is responsible for the enhanced gp2b 3a receptor activation that is enhanced gp2b
3a fibrinogen receptor mediated crosslinking of platelets and platelet aggregation now on the other hand activation of g protein coupled gq pathway stimulates a phospholipase c now this phospholipc it hydrolyzes pip2 that is a phosphatidyl iosutol 4-5 bisphosphate it is a membrane bound protein so it causes hydrolysis of pip2 now this results in hydrolysis of
Pip2 results in the uh production of diacylglycerol and ip3 that is inositol triphosphate now dhe there is a dioxide lystrol and ip3 they are very important secondary messengers now ip3 stimulates release of calcium from smooth endoplasmic reticulum now this calcium it degranulates uh it causes the rupture of dense granules which are present in the platelets
And which causes further release of adp and 5ht now this adp it further stimulates p2 y12 receptors now apart from this it is a diastyle glystrol which stimulates a protein kinase c now stimulation of protein kinase c further stimulates gp2b3a fibrinogen receptors and this again and uses cross-linking activation of this receptor induces cross-linking with
Other platelets through fibrinogen and this diagram it clearly explains the immense or very high potential of adp in inducing the platelet aggregation so clopidogrel it blocks its p2 y12 receptors and it prevents uh stimulation of gp 2b 3a receptors and it also inhibits the release of pro aggregatory adp it also inhibits the release of adp which is responsible
For platelet aggregation so a mechanism of action of clopidogrel flopidogram blocks p2 y12 adp receptors inhibits adp mediated activation of key that is the final gp2b 3a receptor and the sclerophytal inhibits adp as well as fibrinogen induced platelet aggregation now let’s talk about the pharmacokinetics of clopidogrel clopidogrel is a slow-acting drug the
Onset of action is four hours narcissistic causes irreversible blockage of platelet p2 y12 receptor the antiplatelet action of clopidogrel lasts for about five to seven days its elimination half life is seven to eight hours and the dose of clopidogrel is 75 milligram once daily now let’s talk about the clinical uses now since tropidogram inhibits uh thrombosis
In arteries uh it prevents transient ischemic attack it prevents stroke and by by inhibiting the formation of thrombus in coronary blood vessels it also inhibits heart attack now it is useful in coronary acute coronary syndrome like unstable angina prevention of mi and peripheral vascular diseases like intermediate claudication and it also reduces incidences
Of restinosis after percutaneous coronary intervention now main adverse effects of clopidogrel are hemorrhage and thrombocytopenia so this is all about the pharmacology of cropidogrel now if you find the video helpful kindly like subscribe and share this video you can ask your questions by writing in the comment section thanks for watching the video you
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Pharmacology of Clopidogrel (Antiplatelet & Antithrombotic) | Dr. Shikha Parmar By Dr.Shikha Parmar Classes
