Skip to main content
UploadLanguage (EN)Support
BusinessMobileSocial MediaMarketingTechnologyArt & PhotosCareerDesignEducationPresentations & Public SpeakingGovernment & NonprofitHealthcareInternetLawLeadership & ManagementAutomotiveEngineeringSoftwareRecruiting & HRRetailSalesServicesScienceSmall Business & EntrepreneurshipFoodEnvironmentEconomy & FinanceData & AnalyticsInvestor RelationsSportsSpiritualNews & PoliticsTravelSelf ImprovementReal EstateEntertainment & HumorHealth & MedicineDevices & HardwareLifestyle
Rahul Bhati, profile picture
Uploaded byRahul Bhati
PPTX, PDF10,218 views

Antiplatelet drugs

Platelets play a key role in arterial thrombosis by sticking to damaged vessel walls and aggregating, releasing substances that promote further platelet activation and aggregation. Antiplatelet drugs target various steps in this process, including thromboxane A2 synthesis via aspirin; ADP receptors via drugs like clopidogrel and ticagrelor; the final common pathway of the glycoprotein IIb/IIIa receptor via abciximab; and thrombin receptors via vorapaxar. While effective for reducing thrombosis, all antiplatelet drugs increase the risk of bleeding to some degree.

Health & Medicine◦
ANTI-PLATELET DRUGS
Role of platelets in thrombosis • In arterial thrombi, platelets are the main constituents. • Platelets first stick to damaged vessel wall and aggregation occurs which lead to release of ADP, TXA2, serotonin other substances which promote further aggregation by activation of Gp IIb/IIIa on surface of the platelets. • Vascular PGI2 is potent inhibitor of platelet aggregation.
Antiplatelet Drugs 1)COX inhibitors Aspirin 2)ADP Receptor blockers Irreversible Ticlopidine, Clopidogrel, Prasugrel Reversible Ticagrelor, Cangrelor 3)GP llb/llla inhibitors Monoclonal antibody Abciximab Synthetic molecules Eptifibatide, Tirofiban 4)PDE inhibitors Dipyridamole, Cilostazol 5) Thrombin Receptor inhibitor Vorapaxar
Platelet adhesion and aggregation
• GPVI and GPIb are platelet receptors that bind to collagen and vWF, causing platelets to adhere to the subendothelium of a damaged blood vessel. • TxA2 is the major product of COX-1 involved in platelet activation. • Prostacyclin (PGI2), synthesized by endothelial cells, inhibits platelet activation.
• PAR-1 and PAR-4 are PARs that respond to thrombin (IIa) • P2Y1 and P2Y12 are receptors for ADP; when stimulated by agonists, these receptors activate the fibrinogen-binding protein GPIIb/IIIa and COX-1 to promote platelet aggregation and secretion.
Sites of action of antiplatelet drugs
Aspirin • Aspirin inhibits TxA2 synthesis by irreversibly acetylating COX-1. • Reduced TxA2 release attenuates platelet activation and recruitment to the site of vascular injury. • Therapeutic Uses-Acute myocardial infarction or acute ischemic stroke & Secondary prevention in patients with stroke, coronary artery disease, or peripheral artery disease.
• COX-1 inhibitor(selectivity>100x over COX-2) • Antithrombotic effect achieved with low doses(<100 mg daily) • Reduced toxicity with lower doses • Higher doses do not improve efficacy and potentially are less efficacious because of inhibition of prostacyclin production, which can be largely spared by using lower doses of aspirin.
• Adverse effects- Risk of gastrointestinal adverse events (ulceration and bleeding) • Lack of response in some patients (aspirin resistance) • Nonsteroidal anti-inflammatory drugs that are reversible inhibitors of COX-1 have not been shown to have antithrombotic efficacy. • May even interfere with low-dose aspirin regimens. • Hence concomitant use with aspirin should be avoided.
ADP Receptor blockers • Ticlopidine, clopidogrel, and prasugrel irreversibly block P2Y12, a key ADP receptor on the platelet surface • Cangrelor and ticagrelor are reversible inhibitors of P2Y12. • Clopidogrel therapeutic uses-Acute coronary syndrome & Secondary prevention in patients with myocardial infarction, stroke, or peripheral artery disease
• Prasugrel, Ticagrelor & Cangrelor used after percutaneous coronary intervention for acute coronary syndrome • Adverse effects- increases the risk of bleeding, particularly intracranial bleeding,
GP llb/llla inhibitors • Abciximab, eptifibatide, and tirofiban inhibit the final common pathway of platelet aggregation by blocking fibrinogen and vWF from binding to activated GPIIb/IIIa. • Therapeutic uses-Coronary intervention for acute coronary syndrome • Adverse Effects- The major side effect is bleeding. Thrombocytopenia occurs in 0.5%–2% of patients.
Dipyridamole • Interferes with platelet function by increasing the intracellular concentration of cyclic AMP, mediated by inhibition of phosphodiesterase or by blockade of uptake of adenosine, thereby increasing the dwell time of adenosine at cell surface adenosine A2 receptors that link to the stimulation of platelet adenylyl cyclase. • Therapeutic uses-secondary prevention of stroke when combined with aspirin.
Thrombin Receptor Inhibitor • Vorapaxar inhibits thrombin-mediated platelet activation by targeting PAR-1(Protease activated receptor), the major thrombin receptor on platelets. • Therapeutic uses-Secondary prevention in patients with a history of myocardial infarction or peripheral artery disease • Adverse Effects- increases the risk of bleeding and is contraindicated in patients with a history of intracranial bleeding, stroke, or transient ischemic attack.
THANK YOU