JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D III Year PHARMACOLOGY - II Previous Question Paper (April/May - 2019 - 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:

• Cyclooxygenase Inhibitors: Aspirin irreversibly inhibits the enzyme cyclooxygenase-1 (COX-1), preventing the formation of thromboxane A2 (TXA2), a potent platelet aggregator and vasoconstrictor.
• P2Y12 Receptor Antagonists: Agents like clopidogrel, prasugrel, and ticagrelor block the ADP receptor on the platelet surface, preventing the activation of the GPIIb/IIIa receptor complex required for fibrinogen binding.
• GPIIb/IIIa Receptor Antagonists: Drugs such as abciximab, eptifibatide, and tirofiban block the final common pathway of platelet aggregation by preventing fibrinogen from binding to the GPIIb/IIIa receptor.
• Phosphodiesterase Inhibitors: Dipyridamole increases intracellular cAMP levels by inhibiting phosphodiesterase, which inhibits platelet activation.

Natural anticoagulants are endogenous proteins that regulate the coagulation cascade to prevent excessive clot formation. Their pharmacological application involves managing hypercoagulable states and preventing thromboembolic events.

Key natural anticoagulants include:

• Antithrombin III (AT-III): A serine protease inhibitor that inactivates thrombin (Factor IIa) and Factor Xa. Its activity is significantly enhanced by heparin. Deficiency in AT-III leads to a hypercoagulable state.
• Protein C and Protein S: Protein C is activated by thrombin bound to thrombomodulin. Activated Protein C (APC), with Protein S as a cofactor, proteolytically inactivates Factors Va and VIIIa, effectively slowing the coagulation cascade.
• Tissue Factor Pathway Inhibitor (TFPI): A protein that directly inhibits the Factor VIIa-Tissue Factor complex, thereby regulating the initiation phase of the extrinsic coagulation pathway.

Therapeutic use of these agents, particularly Protein C concentrates or recombinant forms, is indicated in severe sepsis or hereditary deficiencies to restore the natural anticoagulant balance.