(4.4) ANTICOAGULANTS (HARD QUIZ)

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Questions and Answers

What is the primary mechanism by which dabigatran exerts its effects?

Binds directly to thrombin (correct)

Inhibits antithrombin III activity

Inhibits Factor Xa activity

Increases platelet aggregation

Which of the following is the recommended reversal agent for dabigatran?

Prothrombin complex concentrate

Andexanet alfa

Vitamin K

Idarucizumab (correct)

In which situation would bivalirudin be indicated?

Patients with renal dysfunction

Patients undergoing major surgery

Patients undergoing percutaneous coronary intervention at risk of HIT (correct)

Patients who require long-term anticoagulation

What is a significant side effect associated with dabigatran?

Bleeding Signup and view all the answers

Which direct thrombin inhibitor is derived from leech saliva?

Bivalirudin Signup and view all the answers

What are the three components of Virchow’s Triad?

Hypercoagulability, venous stasis, endothelial injury Signup and view all the answers

Which role do Protein C and Protein S play in the clotting cascade?

They function as natural anticoagulants. Signup and view all the answers

How does Antithrombin III contribute to anticoagulant activity?

By inhibiting thrombin and factor Xa Signup and view all the answers

What does a change in INR indicate in terms of the coagulation process?

It reveals the efficiency of the extrinsic pathway and warfarin therapy. Signup and view all the answers

Which of the following is a common adverse event associated with anticoagulants?

Excessive bleeding or hemorrhage Signup and view all the answers

What is the drug of choice for treating blood clots in pregnant patients?

Heparin Signup and view all the answers

What effect does Antithrombin III deficiency have on pharmacotherapeutic selection?

It necessitates higher doses of unfractionated heparin. Signup and view all the answers

Which of the following drugs does not have a specified reversal agent?

Fondaparinux Signup and view all the answers

What are the common conditions hinted under Virchow’s Triad that can lead to thrombosis?

Varicose veins and hypercoagulability Signup and view all the answers

In the context of hemostasis, what characterizes a fibrin-rich clot?

Linked to cardioembolic strokes from atrial fibrillation Signup and view all the answers

Which pathway is assessed by the Activated Partial Thromboplastin Time (aPTT)?

Intrinsic and Common pathways Signup and view all the answers

What is the normal range for Prothrombin Time (PT)?

11-13.5 seconds Signup and view all the answers

Which of the following conditions does not typically contribute to the formation of a thrombus?

Cardioembolic strokes Signup and view all the answers

What is a primary characteristic of a platelet-rich clot?

Found in myocardial infarction events Signup and view all the answers

Which of the following phrases correctly describes the intrinsic pathway of the clotting cascade?

Measuring aPTT assesses its efficacy Signup and view all the answers

Which statement about anticoagulants is incorrect?

Dabigatran is primarily monitored through aPTT. Signup and view all the answers

What is the primary mechanism of action for indirect Factor Xa inhibitors like fondaparinux?

Inhibition of factor Xa via antithrombin III binding Signup and view all the answers

Which of the following side effects is exclusively associated with rivaroxaban?

Increased treatment failure on an empty stomach Signup and view all the answers

Which patients should avoid the use of fondaparinux?

Patients with end-stage renal disease Signup and view all the answers

How is andexanet alfa used in the context of direct Factor Xa inhibitors?

As a reversal agent for anticoagulation Signup and view all the answers

What indicates a difference in the mechanism between direct and indirect Factor Xa inhibitors?

Inhibition of factor Xa through direct binding Signup and view all the answers

Which of the following is NOT a common clinical indication for direct Factor Xa inhibitors?

Management of HIT Signup and view all the answers

What is a key concern when administering rivaroxaban to patients?

There is a risk of increased treatment failure on an empty stomach Signup and view all the answers

What is a primary feature of the elimination of fondaparinux?

Renal clearance Signup and view all the answers

Which of the following statements regarding the dosing of andexanet alfa is accurate?

Dosing is based on the dose of factor Xa inhibitor and timing of the last dose Signup and view all the answers

What function does antithrombin III serve in the context of fondaparinux?

It inhibits factor Xa when complexed with fondaparinux. Signup and view all the answers

Which vitamin K-dependent clotting factors are specifically inhibited by warfarin?

Factor II, VII, IX, and X Signup and view all the answers

What is the primary purpose of therapeutic anticoagulation?

To prevent clot formation and allow the body to dissolve existing clots Signup and view all the answers

In the case of a single factor deficiency, which coagulation factor is most likely affected if both aPTT and PT are prolonged?

Factor VII Signup and view all the answers

What is the mechanism of action for warfarin?

Inhibition of vitamin K epoxide reductase complex 1 (VKORC1) Signup and view all the answers

Which of the following best describes the pharmacokinetics of warfarin?

Slow onset and may take 3-5 days to fully deplete clotting factors Signup and view all the answers

Which of the following anticoagulants requires bridging therapy when initiating treatment?

Warfarin Signup and view all the answers

Which reversal agent is preferred for life-threatening bleeds caused by warfarin?

4-Factor Prothrombin Complex Concentrate (4F-PCC) or FFP along with vitamin K1 Signup and view all the answers

Which factor has the longest half-life among these coagulation factors?

Factor II Signup and view all the answers

What common misconception might lead to incorrect assumptions about the initial risk when a patient starts warfarin therapy?

Patients are at risk of hypercoagulability initially Signup and view all the answers

What is the main difference in the onset time for clotting factor reversal between 4F-PCC and FFP?

4F-PCC can have an onset of 20-30 minutes while FFP takes 3-5 hours Signup and view all the answers

Study Notes

Lecture #27: Anticoagulant Pharmacology

Lecture presented by Brian Skinner, PharmD, BCPS, Associate Professor of Internal Medicine at Marian University – College of Osteopathic Medicine. The lecture covered BMS 551 Med Phys Pharm in Fall 2024.

Objectives

Define hemostasis, its clinical manifestations, and general therapeutic strategies for treatment.
Recall the three components of Virchow's Triad and recognize examples of each.
Diagram the clotting cascade and correlate how anticoagulants disrupt the cascade.
Describe the roles of Antithrombin III, Protein C, and Protein S in the clotting cascade.
Relate how changes in aPTT, PT, and INR are reflected in the clotting cascade, and how they are utilized for therapeutic drug monitoring.
Identify the mechanism of action, dosage form, adverse events, and contraindications of anticoagulants and thrombolytics discussed in the lecture.
Recall the drug of choice for treatment and prophylaxis of blood clots in pregnant patients.
Identify the antidotes associated with warfarin, heparin products, factor Xa inhibitors, and directed thrombin inhibitors, and how they work.
Predict the impact of Antithrombin III deficiency on pharmacotherapeutic selection.
Given a simplified patient case, recommend the most appropriate pharmacotherapeutic strategy.
Lecture notes include figures from Principles of Pharmacology by Baca, Golan (Chapter 22) and Lippincott Illustrated Reviews: Pharmacology 6e Yellepeddi (Chapter 22).

Drug List

A table listing various drugs (e.g., Heparin, Enoxaparin, Apixaban, Rivaroxaban, Fondaparinux, Argatroban, Bivalirudin, Dabigatran, Warfarin, Alteplase) with their mechanism of action, how they are supplied (oral or injectable), adverse effects, contraindications (including pregnancy), therapeutic indications, and reversal agents. Important note: some entries are listed as having "NONE" in the reversal agent column.

Hemostasis and Thrombosis

Hemostasis is the process of stopping blood flow.
Thrombosis, the most common abnormality of hemostasis, involves the formation of blood clots.
- Platelet-rich clots (white thrombus) are associated with myocardial infarction (MI) and transient ischemic attacks (TIAs).
- Fibrin-rich clots (red thrombus) are related to cardioembolic strokes, deep vein thrombosis (DVT), and pulmonary embolism (PE). Peripheral clots are also discussed.

Virchow's Triad

The Virchow's Triad consists of three factors contributing to thrombus formation: circulatory stasis, endothelial injury, and hypercoagulability.
- Examples of circulatory stasis: immobility, venous obstruction (from obesity or tumor), pregnancy, varicose veins, and atrial fibrillation.
- Examples of endothelial injury: trauma, cellulitis, atherosclerosis, and venepuncture
- Hypercoagulability is also listed

Clotting Cascade

Simplified diagrams of the intrinsic and extrinsic pathways of the clotting cascade, highlighting the common pathway and the interaction with anticoagulants like antithrombin.
The relationship between the clotting cascade, aPTT, PT, and INR and therapeutic drug monitoring is also covered

Understanding Bleeding Times

Discusses activated partial thromboplastin time (aPTT), prothrombin time (PT), and the calculation of INR. Normal values and uses of the tests are highlighted. Unfractionated Heparin Efficacy and warfarin efficacy (using PT/INR*) are both noted.

Comprehension Check #1

A patient case study presents a scenario where a patient undergoes a motor vehicle accident.
Blood results (aPTT and PT) are cited, and the goal is to determine which clotting factor is most likely affected.

Anticoagulants

Anticoagulants are used therapeutically and prophylactically (to treat and prevent) thrombotic disease.
Key classes of anticoagulants covered include Vitamin K Antagonists (like Warfarin), Factor Xa Inhibitors, Direct Thrombin Inhibitors, and their mechanisms.

Vitamin K Antagonists: Warfarin

Mechanism of Action: Warfarin inhibits vitamin K-dependent clotting factors. The lecture includes the inhibition complex breakdown and discussion of vitamin K as a cofactor.
Therapeutic Uses: treatment and prevention of DVT, PE, cardioembolic stroke, and those with prosthetic heart valves.
Adverse Effects: bleeding and skin necrosis.
Monitoring: Goal INR usually between 2 and 3.
Reversal Agent: Includes vitamin K1, 4F-PCC, and FFP options for different patient needs and complexities

Heparin Products: Unfractionated Heparin and LMWHs (enoxaparin)

Antithrombin III; Unfractionated heparin mechanism and formulation specifics. Anticoagulant properties. Clinical uses; prophylaxis and regular treatment.
Adverse effects include bleeding and heparin-induced thrombocytopenia (HIT).
Reversal agent: Protamine Sulfate; limitations for LMWHs.

Fondaparinux

A synthetically derived pentasaccharide anticoagulant. Injectable formulations only. Mechanism of action and in relation to antithrombin III and factors Xa.
Indications often include prevention and treatment for DVT & PE.
Side effects and contraindications are noted.
No established reversal agent.

"Direct" Factor Xa Inhibitors: Rivaroxaban and Apixaban

Mechanism of action: Inhibiting factor Xa independent of antithrombin activity.
Indications include treatment & prevention of venous thromboembolism (VTE) and stroke from atrial fibrillation.
Side effects include increased bleeding risk or treatment failure when taken with an empty stomach; caution for patients with renal disease.
Reversal agent: Andexanet alfa is mentioned. Mechanism of action is described.

Direct Thrombin Inhibitors: Dabigatran

Dabigatran inhibits thrombin independently of antithrombin.
Oral tablets; used for treatment and prevention of DVT, PE, and cardioembolic stroke.
Side effects include high bleeding risk; contraindicated in patients with renal disease.
Reversal agent: Idarucizumab. Action and use are described

Direct Thrombin Inhibitors: Bivalirudin and Argatroban

Mechanisms involving inhibition of thrombin; these are IV-only anticoagulants.
Indications include specific clinical uses (e.g., PCI, DVT, HIT).
Side effects involve bleeding.
No available reversal agent.

Thrombolytics - Alteplase

Treatment goal: acutely eliminating formed clots.
Reserved for high-risk patients (including ischemic strokes, high-risk PE, STEMI), and catheter clearance.
Given intravenously.
Highly increased bleeding risk is a major concern.
Contraindications to IV tPA use for acute ischemic stroke are listed.

Comprehension Checks #1 and #2

Comprehension check questions involving patient cases and appropriate anticoagulant choices for patients with specific conditions (including CKD).

Additional Notes

Several slides include diagrams illustrating the mechanisms of action of various anticoagulants, relationships, and therapeutic strategies.

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Description

This quiz covers key concepts from Lecture #27 on Anticoagulant Pharmacology, presented by Brian Skinner. It explores hemostasis, Virchow's Triad, the clotting cascade, and the roles of Antithrombin III, Protein C, and Protein S. Furthermore, it discusses anticoagulants, their mechanisms, and therapeutic drug monitoring.