Thrombolytics and Their Mechanisms

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Questions and Answers

What is the main role of plasmin in the fibrinolytic process?

To cleave crosslinked fibrin into degradation products (correct)

To activate plasminogen

To bind to fibrinogen

To form new fibrin polymers

Which factor inhibits the activity of tissue plasminogen activator (t-PA)?

Plasminogen activator inhibitor (correct)

Fibrinogen

Alpha-2-macroglobulin

Antithrombin III

What is the origin of recombinant tissue plasminogen activator (t-PA)?

Produced by bacterial cultures

Derived from animal tissue

Synthesized in hepatocytes

Produced by human endothelial cells (correct)

Streptokinase functions primarily as what type of agent?

Plasminogen activator Signup and view all the answers

How does fibrinolytic therapy impact patients with ST-segment elevation myocardial infarction when administered timely?

It reduces mortality Signup and view all the answers

Which recombinant tissue plasminogen activator (tPA) is specifically known for being 'clot selective'?

Alteplase (Activase®) Signup and view all the answers

What is a significant contraindication for the administration of streptokinase?

Previous administration of streptokinase Signup and view all the answers

Which of the following is true concerning recombinant tPAs compared to streptokinase?

Recombinant tPAs are less antigenic than streptokinase. Signup and view all the answers

What is a primary action of streptokinase as a treatment?

It activates existing plasminogen. Signup and view all the answers

Which of the following best describes the administration of fibrinolytic therapy for ST-segment elevation myocardial infarction?

It significantly reduces mortality if given within 12 hours of symptom onset. Signup and view all the answers

What is the ultimate goal of antithrombotic therapy?

Prevention of thrombosis without inducing bleeding Signup and view all the answers

How does St. John's wort interact with clopidogrel?

It increases the activity of CYP3A4, enhancing clopidogrel activation Signup and view all the answers

Which substance is known for its anti-platelet properties?

Ginkgo biloba Signup and view all the answers

Which of the following best describes the effect of garlic in relation to anticoagulants?

Inhibits platelet aggregation and enhances fibrinolytic activity Signup and view all the answers

What is a common risk when using anticoagulants in combination with antiplatelet agents?

Increased risk of bleeding Signup and view all the answers

What is the primary function of Urokinase in the body?

It acts as a trypsin-like plasminogen activator. Signup and view all the answers

Which condition is NOT a contraindication for the use of Fibrinolytics?

DVT (Deep Vein Thrombosis) Signup and view all the answers

What is a potential side effect of using Fibrinolytics?

Cerebral hemorrhage Signup and view all the answers

Which substance is known to inhibit plasminogen and plasmin?

Aprotinin Signup and view all the answers

In which pregnancy category do most fibrinolytics fall?

Category C Signup and view all the answers

What factor does NOT affect the crossing of drugs to the placenta?

Color of the drug Signup and view all the answers

Which of the following is NOT a method for reversing fibrinolytic effects?

Citrated plasma Signup and view all the answers

How does α2-antiplasmin function in regards to plasmin?

It inactivates plasmin. Signup and view all the answers

What is the primary purpose of thrombolytic drugs?

To disintegrate existing thrombus Signup and view all the answers

Which of the following is NOT a plasminogen activator?

Warfarin Signup and view all the answers

What is the endogenous fibrinolytic agent in the body?

Plasmin Signup and view all the answers

How do thrombolytics differ from anticoagulants?

Thrombolytics break down existing clots, while anticoagulants only prevent their growth. Signup and view all the answers

Which of the following statements about fibrinolytics is incorrect?

They prevent the formation of new clots. Signup and view all the answers

What role does plasminogen play in the fibrinolytic system?

It is converted into plasmin to dissolve clots. Signup and view all the answers

Which of the following drugs is considered a recombinant tissue plasminogen activator (tPA)?

Alteplase Signup and view all the answers

Which statement best describes a major side effect of thrombolytics?

They can cause excessive bleeding. Signup and view all the answers

Study Notes

Thrombolytics

Thrombolytics (clot busters) are used to dissolve existing blood clots.
Thrombolytics are used when platelet inhibitors and anticoagulants are ineffective at breaking up clots.
Endogenous fibrinolytic plasmin is activated from zymogen plasminogen.
Plasminogen activators include tissue plasminogen activator (tPA), recombinant tPAs, streptokinase, and urokinase.

Thrombolytics: Mechanism of Action

Thrombolytics activate plasminogen, which breaks down fibrin, the protein that forms blood clots.
Plasminogen activators bind to fibrin, forming a complex that activates plasminogen.
Once activated, plasmin breaks down fibrin, dissolving the clot.
There are natural inhibitors for this system including plasminogen activator inhibitor 1 or 2, and α2-antiplasmin.

Streptokinase

Streptokinase is a plasminogen activator extracted from streptococci bacteria.
It is administered intravenously.
It is effective in treating ST-elevation myocardial infarction (STEMI) when administered within 12 hours of symptom onset.
Streptokinase can cause antibody formation, which can reduce its effectiveness and lead to allergic reactions.
It is contraindicated for patients who have received it previously due to the risk of anaphylaxis.

Recombinant tPAs

Recombinant tPAs are human-made versions of tPA.
They are less antigenic, reducing the chance of allergic reactions.
Examples of recombinant tPAs include alteplase (Activase®) and reteplase (Retavase®).
Alteplase is clot-selective, meaning it targets fibrin-bound plasminogen.
Reteplase has a longer half-life.

Urokinase

Urokinase is a trypsin-like plasminogen activator produced by the kidneys and excreted in urine.
It can be administered intravenously or by catheter.
It is effective in treating deep vein thrombosis (DVT) and pulmonary embolism (PE).

Side Effects of Fibrinolytics

Common side effects include bleeding, gastrointestinal hemorrhage, and cerebral hemorrhage.
Fibrinolytics are contraindicated in patients with invasive procedures, hemorrhagic cerebrovascular disease, serious gastrointestinal bleeding, hemorrhagic disorders, and severe uncontrolled hypertension.

Reversal of Fibrinolytic Effects

α2-antiplasmin, a plasma protein, rapidly inactivates plasmin.
Aprotinin is a polypeptide that inhibits plasmin, tPA, and thrombin. It can increase the risk of postoperative acute renal failure.
Aminocaproic acid and tranexamic acid inhibit plasminogen and plasmin but may not increase the risk of postoperative acute renal failure.
Fresh plasma provides coagulation factors.

Fibrinolytics in Pregnancy

Most fibrinolytics are categorized as pregnancy category C, meaning their use is difficult to recommend.
Drugs with a molecular weight higher than 1,000 Daltons often do not cross the placental barrier.

General Drug Interactions

Bone marrow suppressants can decrease platelet production, increasing the risk of bleeding.
Anticoagulants, antiplatelet agents, and fibrinolytics all increase bleeding risk.
Herbal supplements like ginkgo biloba, St. John's wort, and garlic can interact with fibrinolytics.
Ginkgo biloba is an antiplatelet agent.
St. John's wort increases the activity of CYP3A4, which may increase the activation of clopidogrel.
Garlic inhibits platelet aggregation and enhances fibrinolytic activity.

Ultimate Goal of Antithrombotic Therapy

The goal of antithrombotic therapy is to prevent thrombosis without causing excessive bleeding.

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Description

This quiz covers the essential aspects of thrombolytics, including their function in dissolving blood clots and their mechanisms of action. It highlights the role of various plasminogen activators, such as tissue plasminogen activator and streptokinase, in the treatment of conditions like myocardial infarction. Test your knowledge on these critical drugs and their applications.