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Drugs Affecting Blood Coagulation

Overview of Blood Coagulation

  • The cardiovascular (CV) system is a closed system that maintains homeostasis via pressure regulation.
  • Blood moves from high-pressure areas to low-pressure areas, with any damage altering flow and potentially harming tissues.

Body's Response to Damage

  • The CV system responds to injury by forming a clot (coagulation), which helps keep blood pressure normal.
  • Procoagulation mode may lead to large clots during major trauma, while plasma enzymes simultaneously work to dissolve these clots to prevent tissue perfusion loss.

Hemostasis Mechanisms

  • Internal mechanisms prevent excessive blood loss, including:
    • Vascular constriction: narrowing of blood vessels at the injury site.
    • Platelet plug formation: platelets adhere to the injury site and aggregate to form a plug.
    • Coagulation cascade activation: a series of biochemical events lead to blood clot formation.
    • Blood clot formation: solid mass forms at the injury to prevent further bleeding.

Coagulation Cascade

  • Initial Injury Response:
    • Vasoconstriction occurs as the first response to injury.
    • Collagen exposure prompts platelet stimulation leading to shape change, substance release, and aggregation.
    • Fibrinogen is converted into fibrin through the intrinsic and extrinsic pathways.

Clotting Factors

  • Definition: Proteins synthesized in the liver that regulate coagulation.
  • Activation Order: Requires activation in a specific order with Vitamin K essential for synthesis.
  • Calcium ions play a crucial role in activating many clotting factors.

Clot Dissolution Importance

  • Uncontrolled clotting can lead to:
    • Loss of flow = tissue hypoxia
    • Tissue hypoxia = cell death.

Pathways of Coagulation

  • Intrinsic Pathway: Triggered within the vascular system, converting prothrombin into thrombin, essential for clot formation internally.
  • Extrinsic Pathway: Triggered by external injury, activating clotting factors upon exposure to thromboplastin, leading to clot formation externally.

Dysfunctional States of Coagulation

  • Thrombosis: Characterized by inappropriate clotting, potentially causing hypoxia or necrosis.
  • Bleeding disorders: Conditions like Hemophilia and thrombocytopenia that result in excessive bleeding.

Drug Classes Affecting Coagulation

  • Antiplatelet Agents:

    • Decrease platelet aggregation and responsiveness.
    • Example: Aspirin, Clopidogrel.
    • Uses include post-MI and peripheral arterial disease.

  • Anticoagulants:

    • Interfere with the coagulation process by acting on the clotting cascades.
    • Examples: Heparin, Warfarin, Dabigatran.
    • Commonly used in DVT, PE treatment, and stroke prevention.

  • Thrombolytic Agents:

    • Dissolve formed clots (thrombi).
    • Examples: Alteplase, Reteplase (for acute myocardial infarction, stroke).

Antiplatelet and Anticoagulant Pharmacokinetics

  • Antiplatelet agents: Can be oral or IV, well absorbed, metabolized in the liver.
  • Anticoagulants: Vary in action time; Heparin has immediate onset, while Warfarin takes longer.

Monitoring Coagulation

  • Clotting Studies: Helper tests for adjusting anticoagulant dosages include:
    • aPTT: Measures intrinsic pathway activity.
    • PT: Measures extrinsic pathway activity.

Antidotes for Overdose

  • Heparin: Treated by Protamine sulfate.
  • Warfarin: Prothrombin complex concentrate for bleeding; Vitamin K for high INR levels.

Conclusion

  • Understanding blood coagulation mechanisms and pharmacological interventions is crucial for managing conditions related to clotting disorders and ensuring patient safety during treatment.