A.21 Anti-Thrombotic Therapy Flashcards
A.21 Anti-Thrombotic TX
Anti-Thombotic Agents
The antithrombotic drugs can be classified into three main categories:
- Antiplatelet Drugs:
- Aspirin: Inhibits thromboxane A2 synthesis by acetylating cyclooxygenase-1 (COX-1).
- Clopidogrel: Irreversibly blocks the P2Y12 ADP receptor on platelets.
- Prasugrel: Similar mechanism to clopidogrel, used for certain patients with acute coronary syndrome.
- Ticagrelor: A reversible inhibitor of the P2Y12 receptor.
- Cangrelor: A reversible P2Y12 inhibitor.
- Gp IIb/IIIa receptor antagonists: Include abciximab, eptifibatide, and tirofiban, which block the final common pathway of platelet aggregation.
- Anticoagulants:
- Vitamin K antagonists: Such as warfarin, which inhibit vitamin K-dependent clotting factors.
- Direct Oral Anticoagulants (DOACs):
- Dabigatran: Direct thrombin inhibitor.
- Rivaroxaban: Factor Xa inhibitor.
- Apixaban: Factor Xa inhibitor.
- Edoxaban: Factor Xa inhibitor.
- Fibrinolytic Agents:
- Used to degrade thrombi. Examples include:
- Tissue Plasminogen Activator (tPA): Commonly used in acute myocardial infarction and stroke.
- Streptokinase: Another agent for thrombolysis, although less commonly used now.
- Urokinase: Used for certain types of thromboembolic events.
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What is Alteplase (tPA)
Alteplase, also known as tissue plasminogen activator (tPA), is a recombinant form of plasminogen activator. It is used as a thrombolytic agent to dissolve blood clots in various medical emergencies, primarily:
- Acute Myocardial Infarction (MI): Used to restore blood flow in patients experiencing a heart attack.
- Acute Ischemic Stroke: Administered to dissolve clots obstructing blood flow to the brain.
- Massive Pulmonary Embolism (PE): Used to treat life-threatening blood clots in the lungs.
Mechanism of Action
Alteplase works by converting plasminogen into plasmin, the enzyme responsible for breaking down fibrin, a key component of blood clots. It preferentially binds to fibrin in clots, promoting localized thrombolysis.
Administration
Alteplase is typically given as an intravenous (IV) infusion, with dosing depending on the specific indication. For acute MI and ischemic stroke, it is often administered within a certain time frame following symptom onset to maximize efficacy.
Side Effects and Risks
Common side effects include bleeding complications, both minor and major. Allergic reactions and hypotension may also occur, though they are less frequent compared to other thrombolytic agents like streptokinase.
Clinical Efficacy
Clinical trials have shown that alteplase is associated with better outcomes than other thrombolytic agents, leading to increased use in acute care settings for rapid intervention against thromboembolic events
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What is the mechanism of action of Alteplase?
A: Alteplase is a tissue plasminogen activator (tPA) that catalyzes the conversion of plasminogen to plasmin, leading to fibrin degradation and thrombus dissolution.
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In what clinical scenarios is Alteplase commonly used?
A: Alteplase is used in the treatment of acute myocardial infarction (MI), acute ischemic stroke, and massive pulmonary embolism (PE).
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How is Alteplase administered for acute MI or ischemic stroke?
A: It is given as an intravenous (IV) infusion over 60–90 minutes, typically involving a total dose of about 90 to 100 mg.
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What are some advantages of using Alteplase over Streptokinase?
A: Alteplase is more effective and has a better safety profile, including lower mortality rates in specific patient populations when compared to Streptokinase.
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Describe the fibrin specificity of Alteplase.
A: Alteplase preferentially activates plasminogen in the presence of fibrin, which helps to localize thrombolysis to the thrombus surface.
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What are common side effects associated with Alteplase administration?
A: Allergic reactions and hypotension are uncommon but can occur; bleeding is a significant risk due to its thrombolytic action.
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What is a clinical trial finding comparing Alteplase and Streptokinase?
A: A trial demonstrated significantly lower mortality with Alteplase in patients with acute MI compared to Streptokinase, especially among those with anterior MI and who presented within 6 hours of symptom onset
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How does Alteplase differ from Tenecteplase?
A: Tenecteplase has a longer half-life and is more fibrin-specific than Alteplase, requiring a single bolus dose compared to the infusion required for Alteplase.
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What is Reteplase?
A: Reteplase is a single-chain, recombinant tissue plasminogen activator (tPA) derivative used to dissolve blood clots in acute myocardial infarction (MI).
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How does Reteplase differ from standard tPA (Alteplase)?
A: Reteplase lacks the finger, epidermal growth factor, and first kringle domains, resulting in a different binding affinity and plasminogen activation profile.
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How is Reteplase administered?
A: Reteplase is administered as two intravenous (IV) boluses, which are separated by 30 minutes.
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What are some key advantages of using Reteplase?
A: Reteplase has a longer plasma half-life compared to tPA and is effective for treating acute MI, though it binds fibrin more weakly.
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Is Reteplase immunogenic?
A: No, unlike streptokinase, Reteplase is not immunogenic, and allergic reactions are rare.
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What is a key consideration regarding the efficacy of reteplase?
A: Clinical trials have demonstrated that reteplase is at least as effective as streptokinase for the treatment of acute myocardial infarction but is not superior to tPA.
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What is the mechanism of action of reteplase?
A: Reteplase activates plasminogen to plasmin, which then breaks down fibrin clots in the bloodstream, facilitating thrombolysis.
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What is the main clinical use of Reteplase?
A: Reteplase is primarily used in the management of acute myocardial infarction to rapidly dissolve thrombi.
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What is Streptokinase?
A: Streptokinase is a thrombolytic agent used to dissolve blood clots by activating plasminogen to plasmin.
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How does Streptokinase activate plasminogen?
A: It forms a 1:1 complex with plasminogen, which induces a conformational change that reveals the active site, allowing the conversion of plasminogen to plasmin.
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What is the affinity of Streptokinase for fibrin?
A: Streptokinase has no affinity for fibrin, meaning it activates both circulating and fibrin-bound plasminogen.
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What are the consequences of Streptokinase activating circulating plasminogen?
A: It leads to the generation of unopposed plasmin, resulting in a systemic lytic state that can cause widespread fibrinolysis.
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What are the common side effects of Streptokinase?
A: Allergic reactions occur in about 5% of patients, which can manifest as rash, fever, chills, and rigors. Transient hypotension is also common due to plasmin-mediated release of bradykinin.
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How is Streptokinase administered for acute myocardial infarction (AMI)?
A: It is typically given as an intravenous infusion of 1.5 million units over 30 to 60 minutes.
