JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D III Year PHARMACOLOGY - II Previous Question Paper (November/December - 2021 - R08)

Antiplatelet agents are drugs that inhibit platelet aggregation, thereby preventing the formation of arterial thrombi. They are primarily used in the management of myocardial infarction, stroke, and peripheral vascular disease. Key classes include:

1. Cyclooxygenase Inhibitors: Aspirin irreversibly inhibits the enzyme cyclooxygenase-1 (COX-1), preventing the formation of thromboxane A2 (TXA2), a potent platelet aggregator and vasoconstrictor.
2. P2Y12 Receptor Antagonists: Drugs like Clopidogrel and Prasugrel irreversibly block the ADP receptor on the platelet surface, preventing the activation of the GPIIb/IIIa complex.
3. Glycoprotein IIb/IIIa Receptor Antagonists: Agents such as Abciximab and Eptifibatide block the final common pathway of platelet aggregation by preventing fibrinogen binding to the GPIIb/IIIa receptor.
4. Phosphodiesterase Inhibitors: Dipyridamole increases intracellular cAMP levels in platelets, which inhibits platelet activation and aggregation.

Natural anticoagulants are endogenous physiological substances that regulate the coagulation cascade to prevent excessive clot formation. Their pharmacological application involves utilizing these mechanisms to manage thromboembolic disorders.

1. Antithrombin III: A serine protease inhibitor that inactivates thrombin (Factor IIa) and Factor Xa. Its activity is significantly potentiated by heparin.
2. Protein C and Protein S: Protein C is activated by thrombin bound to thrombomodulin. Activated Protein C (APC), in the presence of its cofactor Protein S, proteolytically inactivates Factors Va and VIIIa, thereby slowing the coagulation cascade.
3. Tissue Factor Pathway Inhibitor (TFPI): This protein inhibits the extrinsic pathway by forming a quaternary complex with Factor Xa, Tissue Factor, and Factor VIIa, effectively shutting down the initiation phase of coagulation.
4. Heparin (Endogenous): Produced by mast cells, it acts as a catalyst for antithrombin III, accelerating the neutralization of clotting factors.

Therapeutic use of these pathways is essential in clinical settings to maintain the balance between pro-coagulant and anti-coagulant forces, particularly in patients with genetic deficiencies in these natural regulatory proteins.