Anticoagulation in Cardiovascular Pharmacology

Anticoagulation

• Anticoagulation is a key area in cardiovascular pharmacology (CRD 203).
• The lecture covers coagulation cascade, platelet activation, aggregation, receptor function, and various pharmacological classes of anticoagulants.
• It also includes cholesterol and lipid-lowering medications like statins, bile acid sequestrants, niacin, fibrates, and ezetimibe.
• The lecture discusses opposing forces in blood clotting (anti-aggregation and pro-aggregation), and the role of endothelial cells in blood flow.
• Platelet activation and adhesion in response to vascular injury initiate the coagulation cascade, locally strengthening the platelet plug.
• The intrinsic and extrinsic pathways of the coagulation cascade are detailed, including the role of specific factors like tissue factor, factor VII, and thrombin. These pathways work together to create a clot.
• Positive feedback loops in the coagulation cascade accelerate thrombin formation.
• Several key pharmacological classes of anticoagulants are mentioned, including aspirin, ADP inhibitors, GP IIb/IIIa inhibitors, heparin and low molecular weight heparins, thrombin inhibitors, warfarin, novel oral anticoagulants, and fibrinolytics. The specific actions of these classes are explored.
• Platelet inhibition involves various receptors and metabolic processes, acting as drug targets. Key targets include ADP, GPIIb/IIIa, TXA2 synthesis, discussed along with their inhibitory effects.
• Aspirin is a COX-1 inhibitor and irreversibly inhibits thromboxane A2 production, inhibiting platelet activity for the lifespan of the platelet (8-10 days).
• ADP inhibitors prevent ADP activation of the P2Y12 receptor, inhibiting platelet aggregation. Medications like Ticlopidine, Clopidogrel, and Prasugrel are detailed.
• GpIIb/IIIa receptor antagonists prevent the final step in platelet aggregation. Examples include Abciximab.

Acute Anticoagulation

• Heparin and LMWH are indirect thrombin inhibitors that must be closely monitored (unpredictable dose/effect).
• Heparin is given intravenously, and LMWH is given subcutaneously.
• Monitoring parameters like aPTT are essential for heparin adjustments. LMWH is generally more predictable, and kidney function monitoring is necessary.

Oral Anticoagulation

• Warfarin (Coumadin) is a vitamin K antagonist. It inhibits vitamin K-dependent clotting factors; response takes 2-7 days.
• Warfarin dosing is individualized, with a starting dose of 5 mg. INR monitoring is crucial. Different INR ranges exist for various medical conditions.
• Warfarin has many drug interactions, both pharmacodynamically and pharmacokinetically, through CYP 450 interactions.
• It has significant interactions with some food items, especially green leafy vegetables rich in vitamin K.
• Warfarin has complications, like bruising and bleeding; vitamin K administration is the antidote. The route of administration (oral or intravenous) depends on severity.
• Warfarin can induce skin necrosis.
• Novel oral anticoagulants (NOACs) are a newer class of anticoagulants. These include Dabigatran, Rivaroxaban, and Apixaban. They are alternative to warfarin for long-term anticoagulation, with predictable dose responses and no monitoring.
• Many NOACs are indicated for stroke prevention in atrial fibrillation and prevention of venous thromboembolism (VTE) after orthopedic surgery and treatment of deep vein thrombosis (DVT).
• Specific dosages and usage considerations exist for these drugs.
• NOACs, however have less severe bleeding complications but more minor ones.

This quiz explores anticoagulation within the context of cardiovascular pharmacology, focusing on the coagulation cascade, platelet activation, and various anticoagulants. It also covers cholesterol-lowering medications and the dynamics of blood clotting. Test your understanding of these crucial concepts in CRD 203.