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 binding to thrombin.

Direct Thrombin Inhibitors (DTIs) bind directly to the active site or the exosite of the thrombin molecule, independent of antithrombin. They are further divided into:

• Univalent DTIs: These bind only to the active site. Examples include dabigatran (oral), argatroban, and melagatran.
• Bivalent DTIs: These bind to both the active site and the exosite-1. Examples include bivalirudin and lepirudin.

Indirect Thrombin Inhibitors require a cofactor, specifically antithrombin III, to exert their anticoagulant effect. They bind to antithrombin, inducing a conformational change that accelerates the inactivation of thrombin and Factor Xa. Examples include unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) like enoxaparin.

NSAIDs, specifically aspirin, are classified as antiplatelets because they irreversibly inhibit the enzyme cyclooxygenase-1 (COX-1) in platelets. By acetylating a serine residue in the active site of COX-1, aspirin prevents the conversion of arachidonic acid to thromboxane A2 (TXA2). Since TXA2 is a potent stimulator of platelet aggregation and vasoconstriction, its reduction significantly inhibits platelet activation for the lifespan of the platelet (7-10 days).

Aspirin is used in various clinical conditions due to its antiplatelet effect:

• Acute Myocardial Infarction (MI): Administered immediately to prevent further clot propagation.
• Secondary Prevention: Used long-term in patients with a history of MI, unstable angina, or coronary artery bypass grafting (CABG) to reduce the risk of future ischemic events.
• Ischemic Stroke and TIA: Used to prevent recurrent thromboembolic strokes.
• Peripheral Arterial Disease: Helps reduce the risk of vascular occlusions in patients with compromised peripheral circulation.
• Atrial Fibrillation: Used in patients who are at low-to-moderate risk of stroke or who cannot tolerate oral anticoagulants like warfarin.