Drugs for Blood Coagulation Flashcards
What is thrombosis?
Unwanted clot formation. A thrombus adheres to the vessel wall, while an embolus floats within the blood. Both can occlude blood vessels.
What are the three main steps of clot formation?
- Platelet activation & aggregation.
- Thrombin formation.
- Fibrin production & cross-linking + stabilization of the clot.
List the steps of platelet aggregation.
- Adhesion to the site of injury.
- Release of intracellular granules.
- Aggregation of the platelets.
What substance released by platelets is a potent platelet aggregator?
Thromboxane A2.
What is the role of ADP in platelet function?
ADP is a platelet activator and aggregator.
What is the function of serotonin in platelet aggregation?
Serotonin enhances platelet aggregation.
What does PAF stand for and what is its function?
PAF stands for Platelet Activating Factor. It activates platelets.
What enzyme converts prothrombin to thrombin in the coagulation cascade?
Factor Xa.
What is the substrate and product of thrombin in fibrin formation?
- Substrate: Fibrinogen.
- Product: Fibrin.
What is the final step in stabilizing a blood clot?
Cross-linking of fibrin strands.
Name three natural mechanisms that prevent excessive clotting.
- Endothelial cells maintaining a non-clotting surface.
- Negative electrical charge preventing platelet adhesion.
- Release of plasminogen activators to break down clots.
What is the function of protein C in preventing excessive clotting?
Protein C degrades coagulation factors when activated.
How does prostacyclin (PGI2) help prevent excessive clotting?
Prostacyclin (PGI2) inhibits platelet aggregation.
When should anti-platelet therapy be initiated after infarction/stroke?
Within 2 hours.
What are the two main goals of anti-platelet therapy?
- Maintain blood flow.
- Limit infarction size.
What other therapies are often used alongside anti-platelet drugs?
Thrombolytic therapy and anticoagulants.
What is the primary mechanism of action of aspirin as an anti-platelet drug?
Selective COX-1 inhibition.
How does aspirin’s COX-1 inhibition affect platelet function?
It blocks thromboxane A2 synthesis in platelets.
What is the typical daily dose range of aspirin for anti-platelet therapy?
81-325 mg/day.
Name two uses of aspirin in cardiovascular disease prevention.
- Transient cerebral ischemia prophylaxis.
- Reduce myocardial infarction.
How does aspirin affect post-myocardial infarction mortality?
It lowers post-myocardial infarction mortality.
In which cardiac condition is aspirin used to prevent coronary thrombosis?
Unstable angina.
What are the two main side effects of aspirin when used as an anti-platelet agent?
- Bleeding.
- Gastrointestinal ulceration.
Why is a low dose of aspirin used for anti-platelet therapy?
For selective inhibition of COX-1.
Which anti-platelet drug works by selectively inhibiting COX-1?
Aspirin.
What is the mechanism of action of ADP Pathway Inhibitors like Ticlopidine and Clopidogrel?
They block ADP receptors on the platelet membrane.
How do ADP Pathway Inhibitors affect platelet function?
They inhibit ADP-mediated platelet activation and GP IIb/IIIa receptors.
Name two examples of ADP Pathway Inhibitors.
Ticlopidine and Clopidogrel.
In what situations are ADP Pathway Inhibitors used as an alternative to aspirin?
For secondary prevention of stroke, myocardial infarction, and unstable angina.
What are three potential side effects of ADP Pathway Inhibitors?
- Neutropenia.
- Thrombocytopenia.
- Aplastic anemia.
Which ADP Pathway Inhibitor is particularly associated with a risk of aplastic anemia?
Ticlopidine.
What is unique about Clopidogrel’s pharmacology?
Clopidogrel is a prodrug that must be activated by liver enzymes.
Which anti-platelet drugs work by blocking ADP receptors on platelet membranes?
ADP Pathway Inhibitors (e.g., Ticlopidine, Clopidogrel).
How do ADP Pathway Inhibitors differ from Aspirin in their mechanism of action?
ADP Pathway Inhibitors block ADP receptors, while Aspirin inhibits COX-1 enzyme.
Why might a doctor choose an ADP Pathway Inhibitor over Aspirin for a patient?
As an alternative when Aspirin is not suitable or effective for secondary prevention of stroke, myocardial infarction, or unstable angina.
What are two examples of Glycoprotein IIb/IIIa Receptor Inhibitors?
Abciximab (a monoclonal antibody) and Eptifibatide.
What is the mechanism of action of Glycoprotein IIb/IIIa Receptor Inhibitors?
They directly block GP IIb/IIIa receptors on platelets.
What are two limitations of Glycoprotein IIb/IIIa Receptor Inhibitors?
- They are expensive.
- They are available only as IV formulations (e.g., Eptifibatide).
What class of drugs does Dipyridamole belong to?
Phosphodiesterase Inhibitors.
What is the mechanism of action of Phosphodiesterase Inhibitors like Dipyridamole?
They increase cAMP levels in platelets.
How do Phosphodiesterase Inhibitors affect platelet function?
They inhibit platelet aggregation.
In what clinical scenario is Dipyridamole used with Warfarin?
For prophylaxis in patients with prosthetic heart valves.
How is Dipyridamole used in combination with Aspirin?
For treatment of angina pectoris.
What is the main side effect of Dipyridamole?
Headache.
Does Dipyridamole increase the risk of bleeding?
No, there is no excess risk of bleeding.
Which antiplatelet drug works by increasing cAMP in platelets?
Dipyridamole.
How do Glycoprotein IIb/IIIa Receptor Inhibitors differ from ADP Pathway Inhibitors in their mechanism?
Glycoprotein IIb/IIIa Receptor Inhibitors directly block GP IIb/IIIa receptors, while ADP Pathway Inhibitors block ADP receptors, indirectly affecting GP IIb/IIIa activation.
What are the two main types of Heparin?
Standard heparin and Low Molecular Weight Heparin (LMWH).
Name two advantages of LMWH over standard heparin.
- Better bioavailability.
- Longer-lasting effect.
What is the primary mechanism of action of Heparin?
It binds to antithrombin III and accelerates its interaction with coagulation factors.
How does Heparin affect thrombin and Factor Xa?
It catalyzes their inhibition by heparin cofactor II and antithrombin III.
List three therapeutic uses of Heparin.
- Deep vein thrombosis.
- Pulmonary embolism.
- Myocardial infarction.
Why is Heparin preferred for pregnant women with venous thromboembolism?
It doesn’t cross the placenta, making it safer for the fetus.
What are the two routes of administration for Heparin?
Subcutaneous (SC) and Intravenous (IV).
How quickly does IV Heparin achieve maximal anti-coagulation effects?
Within minutes after injection.
How is Heparin dosage prescribed?
On a unit basis rather than milligram basis.
What are the two main adverse effects of Heparin?
Bleeding and thrombocytopenia.
List three conditions in which Heparin is contraindicated.
- Recent surgery.
- Severe hypertension.
- Thrombocytopenia.
What advantage does LMWH have in terms of monitoring?
It requires less monitoring than standard heparin.
Name two examples of LMWH.
Dalteparin and Enoxaparin
How does Heparin affect blood clotting in vitro and in vivo?
Heparin inhibits blood clotting both in vitro and in vivo.
What is the primary mechanism of action of Warfarin?
It acts as a Vitamin K antagonist.
How does Warfarin affect clotting factors?
It interferes with the production of vitamin K-dependent clotting factors (II, VII, IX, X).
What is the result of Warfarin’s effect on clotting factors?
It causes the formation of incomplete clotting factors.
How is Warfarin administered?
Orally.
How does Warfarin differ from Heparin in terms of in vitro and in vivo effectiveness?
Warfarin is only effective in vivo, while Heparin works both in vitro and in vivo.
What are two main clinical uses of Warfarin?
- Venous thrombosis.
- Pulmonary embolism.
What is the primary side effect of Warfarin?
Bleeding.
Why is Warfarin contraindicated during pregnancy?
It can cross the placenta and cause fetal abnormalities or bleeding.
List three contraindications for Warfarin use.
- Active or past gastrointestinal ulceration.
- Thrombocytopenia.
- Liver or kidney disease.
How does recent surgery affect the use of Warfarin?
Recent surgery is a contraindication for Warfarin use due to increased bleeding risk.
Why is severe hypertension a contraindication for Warfarin?
Severe hypertension increases the risk of bleeding complications with Warfarin.
Which oral anticoagulant works by antagonizing Vitamin K?
Warfarin.
Name the four vitamin K-dependent clotting factors affected by Warfarin.
Factors II, VII, IX, and X.
What is the main purpose of thrombolytic therapy?
Rapid lysis of already-formed clots
What is the primary mechanism of action of thrombolytic drugs?
They activate plasminogen to plasmin.
How does plasmin affect blood clots?
Plasmin breaks down fibrin in clots.
What initiates the thrombolytic process?
Plasminogen activators.
What are two examples of first-generation (non-selective) thrombolytic drugs?
Streptokinase and Urokinase.
List three clinical uses of Streptokinase.
- Acute pulmonary embolism.
- Venous & arterial thrombosis.
- Acute myocardial infarction.
What are the two main side effects of Streptokinase?
Bleeding and hypersensitivity reactions.
What are two clinical uses of Urokinase?
- Severe pulmonary emboli.
- Deep vein thrombosis.
What is the primary side effect of Urokinase?
Bleeding.
How do thrombolytic drugs differ from anticoagulants in their primary action?
Thrombolytics break down existing clots, while anticoagulants prevent new clot formation.
Which thrombolytic drug is associated with hypersensitivity reactions?
Streptokinase.
In the context of thrombolytic therapy, what is the role of plasminogen?
Plasminogen is converted to plasmin, which then breaks down fibrin in clots.
Why are Streptokinase and Urokinase considered “non-selective” thrombolytics?
They activate both circulating and clot-bound plasminogen, potentially increasing bleeding risk.
What is the full name of tPA?
Tissue-type plasminogen activator (now known as Alteplase).
List three clinical uses of Alteplase.
- Myocardial infarction.
- Pulmonary embolism.
- Acute ischemic stroke.
What advantage does Alteplase have over first-generation thrombolytics?
It is more effective on older clots.
Within what time frame should Alteplase be administered for acute ischemic stroke?
Within 3 hours of stroke onset.
What are the main side effects of Alteplase?
Bleeding, including gastrointestinal and cerebral hemorrhages.
Name two examples of third-generation thrombolytic drugs.
Reteplase and Tenecteplase.
What is Anistreplase?
A preformed complex of streptokinase and plasminogen.
How does Anistreplase differ from other thrombolytics in terms of its pharmacology?
It acts as a prodrug.
Which thrombolytic drug should be administered within 3 hours of an ischemic stroke?
Alteplase (tPA).
How does Alteplase’s selectivity compare to first-generation thrombolytics?
Alteplase is more selective, preferentially activating fibrin-bound plasminogen
What is the main risk associated with all thrombolytic drugs, including Alteplase?
Bleeding complications.
In what way is Anistreplase related to first-generation thrombolytics?
It contains streptokinase, which is a first-generation thrombolytic.
What are the two main purposes of drugs used to stop bleeding?
- To counteract the effects of anticoagulants and thrombolytics.
- To stop or prevent excessive bleeding.
What is the primary use of Aminocaproic acid and Tranexamic acid?
To counteract the effects of thrombolytic drugs (e.g., alteplase, streptokinase, urokinase).
What is a potential side effect of Aminocaproic acid and Tranexamic acid?
Risk of intravenous thrombosis.
List three side effects of Protamine sulfate.
Bradycardia, hypotension, and flushing.
What anticoagulant does Vitamin K counteract?
Warfarin.
Why does Vitamin K have a slow response in reversing warfarin’s effects?
It takes about 24 hours due to the time needed for new coagulation factor synthesis.
What is the purpose of using Sodium bicarbonate in the context of bleeding control?
To treat aspirin toxicity.
How does Sodium bicarbonate work to treat aspirin toxicity?
It increases renal elimination of aspirin.
What is the primary use of Aprotinin?
To inhibit streptokinase-induced bleeding.
Which drug is used to reverse the effects of heparin?
Protamine sulfate.
Which drugs are used to counteract the effects of thrombolytic drugs like alteplase?
Aminocaproic acid and Tranexamic acid.
Why might there be a delay in the effect of Vitamin K when used to counteract warfarin?
Because it takes time for new coagulation factors to be synthesized.
What is the main purpose of Protamine sulfate?
To reverse the anticoagulant effect of heparin.
