Dr. Declan McKernan
Contact: declan.mckernan@universitygalway.ie
Course: PM309 Cardiovascular Drugs
Objective 1: Compare and contrast different types of anticoagulant drugs
Mechanisms of action
Pharmacokinetics
Side effects
Objective 2: Compare and contrast different types of fibrinolytic drugs
Mechanisms of action
Pharmacokinetics
Side effects
Definition: Drugs used to treat and prevent thrombotic diseases
Classes of anti-coagulants:
Vitamin K Antagonists (e.g., Warfarin)
Unfractionated & Low Molecular Weight Heparins (LMWHs)
Selective Factor Xa Inhibitors
Direct Thrombin Inhibitors
Selectivity:
Least selective: Warfarin & Heparin
Most selective: Factor Xa & Thrombin inhibitors
Mechanism: Prevent the formation of a stable fibrin meshwork
Action duration:
Heparins & thrombin inhibitors: Immediate effect
Warfarin: Takes several days
Definition: Fat-soluble vitamin necessary for coagulation factor synthesis
Mechanism of Action:
Inhibits Vitamin K epoxide reductase (VKORC1) preventing coagulation factor synthesis
Delayed action due to half-lives of coagulation factors (6-60 hrs)
Clinical Uses:
Prevent thrombosis in high-risk patients (DVT, PE, prosthetic valves)
Absorption & Binding: Orally bioavailable, rapid absorption, small volume of distribution
Binding: 99% bound to albumin
Metabolism: CYP2C9 polymorphism leading to variable half-life (~36 hrs)
Monitoring: Requires regular INR checks (2-4 INR target) due to narrow therapeutic index
Contraindications: Pregnancy and breastfeeding; significant drug-drug interactions
Definition: Standardized measure of prothrombin time adjusted for sensitivity index
Purpose: Adjust warfarin dosing to maintain INR within therapeutic range
Description: Family of glycosaminoglycans derived from liver
Mechanism of Action:
Activates antithrombin III (AT III) to inhibit thrombin (IIa) and factor Xa
Unfractionated heparin (UFH) has a broader mechanism than LMWHs
Clinical Uses: Treatment and prevention of thrombosis (DVT, PE, atrial fibrillation)
Administration: Given IV or SC; not absorbed from GIT
Action time: Immediate after IV administration
Monitoring: Activated partial thromboplastin time (APTT) for dosing
Side Effects: Hemorrhage, heparin-induced thrombocytopenia, hypoaldosteronism, and osteoporosis
Mechanism of Action: Selectively inhibit factor Xa, no effect on thrombin
Examples: Fondaparinux, rivaroxaban, apixaban
Clinical Uses: DVT prevention and treatment; can be used in heparin-induced thrombocytopenia cases
Pharmacokinetics: Fondaparinux given SC; rivaroxaban & apixaban are orally available
Side Effects: Bleeding, anemia, nausea
Mechanism of Action: Directly inhibit thrombin, negligible effect on factor Xa
Examples: Dabigatran, argatroban, lepirudin
Clinical Uses: Specific thrombosis types, particularly post-hospitalization
Pharmacokinetics: Some administered IV; dabigatran is an orally bioavailable prodrug
Side Effects: Bleeding, hypersensitivity reactions
Mechanism of Action: Activators that convert plasminogen to plasmin, degrading fibrin
Examples: Streptokinase, alteplase, tenecteplase
Clinical Uses: Acute myocardial infarction management; should be administered promptly
Side Effects: Risk of bleeding, particularly hemorrhagic stroke
Inhibitors of Anticoagulants:
Mechanism: Heparin antagonist (protamine) for reversing heparin effects
Use: Life-threatening hemorrhage or heparin excess
Anti-fibrinolytics:
Mechanism: Inhibit plasmin and plasminogen (e.g., tranexamic acid)
Use: Reduce perioperative bleeding
Thrombus Components:
Fibrin forms the framework; trapped blood cells create the thrombus
Coagulation Mechanism: Involves platelet activation, coagulation factors, and vascular endothelial cells
Fibrinolytic Control: Tissues and plasma contain activators and inhibitors that regulate fibrinolysis