Module C: Antithrombotic and Thrombolytic Drugs

Question 1

Normal Hemostasis

Answer 1

vasoconstriction followed by formation of a platelet plug and a fibrin clot
-once vessel is repaired, clot is removed via fibrinolysis

Question 2

What causes Platelet Aggregation

Answer 2

• exposure to vessel wall collagen
• due to release of thromboxane A2 (TXA2) which arises from conversion of phospholipid membrane in vessel wall to arachidonic acid, which is further metabolized to thromboxane A2

Question 3

Red or Venous Thrombi

Answer 3

thrombi comprised of a few platelets, fibrin, and RBCs

Question 4

White or Arterial Thrombi

Answer 4

thrombi comprised mainly of platelets

-arterial thrombi cause local schema, venous thrombi cause pulmonary emboli

Question 5

Anticoagulants

Mode of Action

Answer 5

-prevent formation or expansion of a thrombus (ie. recurrent PE, DVT, acute MI)
-classified based on mechanism of action
: vitamin K antagonists (Warfarin)
: drugs that potentiate antithrombin III (Heparin)
: drugs that directly inhibit thrombin or active factor X (Dabigitran)

Question 6

Coumadin (Warfarin)

Answer 6

PO

• blocks Vitamin-K dependent steps of coagulation cascade; acts as “false Vitamin K”
• onset of action=3-5 days
• effectiveness of dosage assess via INR
• drug interactions common= can result in excess bleeding
• excess bleeding Tx by withholding Warfarin, Tx with Vitamin K

-used for long-term Tx of DVT, afib, artificial valve replacements

Question 7

INR

Answer 7

international normalized ration

Question 8

Heparin

Answer 8

• endogenous compound found in mast cells, basophils, and vascular endothelium
• must be given parentally
• helps maintain normal hemostasis
• potentiates inactivation of clotting factors by antithrombin III
• unfractionated heparin inactivates thrombin and active factor X
• low molecular weight heparin and fondaparinux primarily inactivate factor X

-used to prevent and Tx venous thromboembolism

Question 9

Ix for Heparin

Answer 9

Tx of acute thromboembolic disorders, including peripheral and PE, venous thrombosis, and disseminated intravascular coagulation
-used phophylactically to prevent clotting in arterial and heart surgery, during blood transfusions, in renal dialysis and blood sample collection

Question 10

Heparin Family

Answer 10

Unfractionated heparin
Low-molecular-weight heparin
Fondaparinux

Question 11

Ix for Fondaparinux

Answer 11

prophylaxis of DVT in pt. having hip # or hip-replacement surgery, or knee-replacement surgery

Question 12

Low-molecular-weight heaprin (LMWH)

Answer 12

ie Inohep (Tinzaparin) and Lovenox (Enoxaparin)
-longer duration of action, less dosing required

Question 13

aPTT

Answer 13

activated partial thromboplastin time - how effectiveness of heparin dosage is assessed

Question 14

Antidote for Heparin

Answer 14

Protamine

• used when there is excessive bleeding
• causes Heparin to dissociate from antithrombin III complex and then binds with heparin to form a salt = resulting in an inactive anticoagulant

Question 15

Dabigitrain

Answer 15

• direct thrombin inhibit
• PO
• does not require INR measurements (very predictable)
• used when increased risk of stroke of PE (DVT, afib)
• CANNOT be currently used with pt. with artificial valves

Question 16

Antiplatelet Drugs

Answer 16

-target different points in process of platelet adhesion and aggregation

Question 17

Mediators released w/ platelet adhesion/aggregation

Answer 17

TXA2
Adenosine Diphosphate (ADP)
Serotonin

Question 18

Aspirin (ASA)

Answer 18

ANTIPLATELET

• inhibits production of thromboxane by interfering with cycleoxygenase, specifically inhibiting production of thromboxane A2
• long lasting effect due to irreversible binding of cycleoxygenase compared to reversibly binding drugs (NSAIDS)

Question 19

Ix for ASA

Answer 19

-low-dose prophylactically for:
stroke
acute and post- MI
CAD
post heart valve surgery

*low dose only inhibits TXA2 and not prostaglandins (PGs)

Question 20

Adverse effects of ASA

Answer 20

GI bleed and excessive bleeding

Question 21

Persantine (Dipyridamole)

Answer 21

ANTI PLATELET

• weak antiplatelet, also a coronary vasodilator
• inhibits platelet adhesion and aggregation
• selectively vasodilates coronary arteries by increasing levels of adenosine in blood (used during chemical stress testing to determine perfusion of coronaries)
• often combined with ASA for preventative Tx of pt. with stroke

Question 22

Fibrinolytic or Thrombolytic Drugs

Answer 22

• enzymes that lyse thrombi by catalyzing formation of plasmin (a nonspecific enzyme that digests fibrin)
• effective in dissolving clots

Question 23

adverse effects of fibrinolytics

Answer 23

GI bleeding, intracranial hemorrhage, minor bleeding, arterial blood gases

Question 24

Ix for fibrinolytics

Answer 24

acute MI, PE, stroke

-administered IV

Question 25

Activase (Alteplase rt-PA)

Answer 25

THROMBOLYTIC

• recombinany (genetically engineered) form of tissue plasminogen activator
• will only activate plasminogen bound to fibrin = will only affect formed thrombi (no preventative effects)
• ONLY thrombolytic recommended for acute PE

Question 26

TNKase (Tenecteplase)

Answer 26

• used with specific type of MI (ST elevation MI-STEMI) which is due to complete occlusion of a major coronary artery
• variant of Alteplase
• more fibrin specific with longer duration of action that Alteplase

Question 27

Tranexamic Acid (TXA)

Answer 27

• agent used to reverse or treat excessive bleeding caused by fibrinolytics
• inhibits activation of plasminogen to plasmin by binding to both plasminogen and plasmin sites