Anticoagulant, Antiplatelet, and Thrombolytic Drugs : Anticoagulant, Antiplatelet, and Thrombolytic Drugs Objectives : Objectives Give a basic overview of the pathways involved in hemostasis, including platelet plug formation and reinforcement of platelet plugs, and mechanisms by which the body protects against widespread coagulation.
Explain the differences between anticoagulant, antiplatelet, and thrombolytic drugs in terms of what coagulation processes they affect and their main clinical uses. Likewise, state the main difference between a thrombus and an embolus.
Describe the usual etiologies of arterial versus venous thrombosis, and discuss how prophylactic or interventional drug therapies for these two situations are similar or different.
Give a short summary of how and where heparins exert their desired anticoagulant effects, and describe the mechanisms and risks of paradoxic increases in thrombotic events associated with heparin-induced thrombocytopenia. Objectives : Objectives Compare and contrast unfractionated heparins and low–molecular weight (LMW) heparins in terms of mechanisms of action, pharmacokinetics, dosing (schedules), suitability for outpatient therapy, and monitoring of response(s).
Summarize the key points that describe the differences between warfarin and heparin: mechanisms, onsets, sites of action, and monitoring.
Compare and contrast the actions and uses of aspirin with those of warfarin and heparin, and state the typical “targets” for the lab test that is used to monitor the response to each.
Summarize instructions about the use of aspirin for relief of common headache, pain, or fever for an outpatient who is taking warfarin; explain situations in which concomitantly taking both warfarin and aspirin is acceptable and situations in which doing so can be dangerous.
Summarize general precautions and guidelines (including drug selection and monitoring) that apply when anticoagulation is indicated for a pregnant woman. In particular, state what the adjustment to the dosage of warfarin should be. Physiology and Pathophysiology of Coagulation : Physiology and Pathophysiology of Coagulation Hemostasis
Stage 1—formation of platelet plug
Intrinsic coagulation pathway
Extrinsic coagulation pathway
Keeping hemostasis under control
Physiologic removal of clots
Venous thrombosis Figure 51-2 Outline of the coagulation cascade showing factors affected by anticoagulant drugs. : Figure 51-2 Outline of the coagulation cascade showing factors affected by anticoagulant drugs. Parenteral Anticoagulants I:Heparin and Related Drugs : Parenteral Anticoagulants I:Heparin and Related Drugs Heparin (unfractionated)
Lungs of cattle
Intestines of pigs
Pulmonary embolism (PE)
Massive deep venous thrombosis (DVT) Parenteral Anticoagulants I: Heparin and Related Drugs : Parenteral Anticoagulants I: Heparin and Related Drugs Adverse effects
– Heparin-induced thrombocytopenia
– Hypersensitivity reactions
Activated partial thromboplastin time (aPTT) Low-Molecular-Weight Heparins : Low-Molecular-Weight Heparins Heparin preparations composed of molecules that are shorter than those found in unfractionated heparin.
Prevention of DVT following surgery
Treatment of established DVT
Prevention of ischemic complications
Adverse effects and interactions
Cost Parenteral Anticoagulants II: Direct Thrombin Inhibitors : Parenteral Anticoagulants II: Direct Thrombin Inhibitors Bivalirudin [Angiomax]
Prevent clot formation (combined with aspirin)
Mechanism of action
Facilitates the actions of antithrombin
Prevents the conversion of fibrinogen into fibrin
Prevents the activation of factor XIIIa
Headache Parenteral Anticoagulants II: Direct Thrombin Inhibitors : Parenteral Anticoagulants II: Direct Thrombin Inhibitors Other direct thrombin inhibitors
Desirudin Warfarin, an Oral Anticoagulant : Warfarin, an Oral Anticoagulant Oral anticoagulant
Antagonist vitamin K
Blocks the biosynthesis of factors VII, IX, X, and prothrombin
Long-term prophylaxis of thrombosis
Prevention of venous thrombosis and associated pulmonary embolism
Prevention of thromboembolism (in patients with prosthetic heart valves)
Prevention of thrombosis during atrial fibrillation Warfarin, an Oral Anticoagulant (cont’d) : Warfarin, an Oral Anticoagulant (cont’d) Adverse effects
Fetal hemorrhage and teratogenesis from use during pregnancy
Use during lactation Warfarin, an Oral Anticoagulant (cont’d) : Warfarin, an Oral Anticoagulant (cont’d) Drug interactions
Drugs that increase anticoagulant effects
Drugs that promote bleeding
Drugs that decrease anticoagulant effects
Acetaminophen Antiplatelet Drugs : Antiplatelet Drugs Aspirin (ASA)
Inhibition of cyclooxygenase
Increase risk of GI bleeding
Inhibits ADP-mediated aggregation
ADP receptor antagonist Antiplatelet Drugs : Antiplatelet Drugs Glycoprotein (GP) IIb/IIIa receptor antagonists
Most effective antiplatelet drugs
Reversible blockade of platelet GP IIb/IIIa receptors Thrombolytic Drugs : Thrombolytic Drugs Streptokinase [Streptase]
Acute coronary thrombosis (acute MI)
Deep venous thrombosis (DVT)
Massive pulmonary emboli
– Antibody production
Fever Thrombolytic Drugs : Thrombolytic Drugs Alteplase
Deep vein thrombosis
Massive pulmonary emboli
– Antibody production
Fever Other Thrombolytic Drugs : Urokinase
Streptokinase vs. Alteplase Other Thrombolytic Drugs