JNTU Pharm. D III Year PHARMACOLOGY - II Previous Question Paper (October - 2019 - R08)

Thrombin inhibitors are anticoagulants that prevent the conversion of fibrinogen to fibrin, thereby inhibiting clot formation. They are classified based on their mechanism of action:

• Direct Thrombin Inhibitors (DTIs): These agents bind directly to the active site of thrombin (both free and clot-bound). Examples include Hirudin (a bivalent inhibitor), Argatroban, and Dabigatran (an oral prodrug). They do not require antithrombin III as a cofactor and are effective in patients with heparin-induced thrombocytopenia.
• Indirect Thrombin Inhibitors: These agents require a cofactor, primarily Antithrombin III (ATIII), to exert their effect. Unfractionated Heparin (UFH) binds to ATIII and induces a conformational change, accelerating the inactivation of thrombin and Factor Xa by 1000-fold. Low Molecular Weight Heparins (LMWH), such as Enoxaparin, primarily inhibit Factor Xa but have less effect on thrombin compared to UFH.

NSAIDs, specifically Aspirin (Acetylsalicylic acid), are classified as antiplatelets because they irreversibly inhibit the enzyme Cyclooxygenase-1 (COX-1) in platelets. By acetylating the serine residue of the enzyme, aspirin prevents the synthesis of Thromboxane A2 (TXA2), a potent mediator of platelet aggregation and vasoconstriction. Since platelets lack a nucleus, they cannot synthesize new COX-1, meaning the antiplatelet effect lasts for the entire lifespan of the platelet (7–10 days).

Aspirin is used clinically for:

• Acute Myocardial Infarction: Administered as an initial dose to rapidly inhibit platelet aggregation and limit thrombus expansion.
• Secondary Prevention: Used in patients with a history of myocardial infarction, stroke, or transient ischemic attacks to prevent recurrent thrombotic events.
• Stable and Unstable Angina: Reduces the risk of progression to myocardial infarction.
• Post-surgical prophylaxis: Used after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) to maintain graft patency and prevent stent thrombosis.