February 1, 2023

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First lets revise relevant physiology from the video of platelet plug formation. we have seen that after injury, platelets adhere to the damaged area. this is followed by platelet activation, and release reaction in which dense granules release adp and alpha granules release fibrinogen. fibrinogen binds with membrane receptor gp iib/iiia. simultaneously, from membrane

Phospholipid, arachidonic acid is generated. cyclooxygenase-1 synthesize thromboxane a2 from it. the thromboxane a2 is released into the surrounding area. also, on the platelet membrane, thrombin is generated as part of it has high level of camp and low level of calcium. this prevents the platelet from sticking to other platelets. this inactive state of platelet is

Also supported by healthy endothelial cells. it acts on platelet receptors and increases the level of camp. high level of camp keeps the gp iib/iiia in inactive state. so, this platelet was not sticking to other platelets. but situation is going to change now because of thrombin, adp and txa2. and thromboxane a2 binds with thromboxane a2 prostaglandin or tp receptor.

In activated platelet, camp level falls and ca level increases. so now this platelet attaches to the adhered platelet likewise, more platelets aggregate and form a plug. acting on different steps in platelet plug formation. like drugs inhibiting synthesis of thromboxane a2, inhibitors of adp receptor p2y12, protease activated receptor antagonist, phosphodiesterase

Inhibitors as these drugs act at different levels, we can get additive so, once the enzyme is inhibited, its inhibited forever. the result is inhibition by aspirin lasts through out the life of platelet. and repeat dose of aspirin produces cumulative effect. a very important thing is, for antiplatelet effect, aspirin should be given at very low dose as compared to the doses

That we use for its other effects. now aspirin inhibits cyclooxygenase in endothelium too. however, at low dose of aspirin this is not a problem so, they can synthesize new enzyme and keep producing pgi2. however, if you give high dose of aspirin, endothelial cells are also affected. so pgi2 synthesis decreases which produces pro-aggregatory effect. so, at high dose,

Anti-aggregatory and pro-aggregatory effects of aspirin but at low dose only platelets are affected so you get anti-platelet effect. reversible cyclooxygenase inhibitors like ibuprofen maintain proper time gap between these drugs to minimize this interaction. drugs in this group are, ticlopidine, clopidogrel and prasugrel. their active metabolites inhibit p2y12 receptor,

So platelets are not activated. now, there is something important about each of them. ticlopidine is associated with sever hematologic adverse events like neutropenia, thrombotic thrombocytopenic purpura and aplastic anaemia. regarding clopidogrel, its activation occurs mainly by cyp2c19. so clopidogrel is not activated and its therapeutic effects are not achieved.

Similarly, activation is also reduced in patients taking inhibitors of this enzyme it is contraindicated in patients with history of transient ischemic attack or stroke ticagrelor and cangrelor are other drugs in this group. they are active and reversible, in contrast to previous drugs it inhibits effect of thrombin and thus reduces platelet activation. phosphodiesterase

Is the enzyme that degrades camp. we know that reduced level of camp favors platelet aggregation. drugs like dipyridamole and cilostazol inhibit phosphodiesterase enzyme. so, camp level stays high which prevents platelet aggregation. now let’s move to the final group, gp iib/iiia inhibitors. we saw that this receptor attaches platelet to other platelets. abciximab,

Eptifibatide and tirofiban block this receptor. so, it cannot attach to other platelet and aggregation is prevented. so, these were all the antiplatelet drugs and their mechanism of action. they are used in unstable angina to reduce the risk of myocardial infarction. in patients of myocardial infarction to reduce reinfarction, in patients with cerebrovascular disease

To reduce the risk of stroke, with prosthetic heart valves to prevent thrombosis on valve, in arteriovenous shunts to maintain patency of the shunt, in venous thromboembolism, peripheral vascular disease, percutaneous coronary intervention, coronary bypass graft implants bleeding is the common adverse event with all antiplatelet drugs. first, we saw aspirin which inhibits

Cycloxygenase-1 inhibits cyclooxygenase in endothelium also which reduces synthesis of pgi2. it should be avoided with reversible cox-1 inhibitors. ticlopidine, clopidogrel and prasugrel are prodrugs ticlopidine is associated with sever hematologic adverse events, due to genetic polymorphism, some patients may not activate clopidogrel, ticagrelor and cangrelor are active

By themselves and inhibit the p2y12 reversibly. dipyridamole and cilostazol inhibit phosphodiesterase abciximab, eptifibatide and tirofiban inhibit gp iib/iiia. these were the mechanism of action of antiplatelet drugs. they are used in unstable angina, myocardial infection, cerebrovascular disease, prosthetic heart valves, arteriovenous shunts, venous thromboembolism,

Peripheral vascular disease, percutaneous coronary intervention, coronary bypass graft implants and intermittent claudication. if you like our videos, subscribe to the channel and join us in the journey,

Transcribed from video
Antiplatelet Drugs: Aspirin, Clopidogrel etc By Nonstop Neuron