Antithrombolytic therapy

Question 1

What is the difference between arterial clots and venous clots?

Answer 1

Arterial = primarily platelets, treat with antiplatelet meds

Venous = primarily fibrin, treat with anticoagulants - inhibit coagulation cascade

Question 2

What are the 4 major antiplatelet therapies?

Answer 2

Cyclooxygenase inhibitors: aspirin (irreversible), NSAIDS (competitive inhibitors- used more for pain relief)

Dipyridamole

GP IIb/IIa inhibitors (this complex is important for getting platelets to stick together)

ADP receptor inhibitors - ticlopidine, clopidogrel, prasugrel, ticagrelor

Question 3

Aspirin mechanism of action

Answer 3

Low doses: blocks thromboxane A2 production –> block platelet aggregation & vasoconstriction

Higher doses: also blocks PGI2 –> blocks prostacyclin production too! Inhibits platelet aggregation & causes vasodilation

Question 4

Dipyridamole mechanism

Answer 4

Increases cAMP production

Blocks Ca release from dense granules, blocking AA production & decreasing thromboxane A2 production

Enhances aspirin’s effect on platelet aggregation

Question 5

Glycoprotein IIb/IIIa inhibitors mechanism of action

Answer 5

Interfere with fibrinogen-induced platelet aggregation

3 classes:
Fab fragments- abciximab
Peptide-bast antagonists - eptifibatide
Small molecule inhibitors- tirofiban

Potent: platelet count –> 0

Abciximab: 30 min half life
Eptifabatide/tirofaban: 2-2.5 hours

Best for short term bc too potent for long term!

Question 6

ADP receptor inhibitors- mechanism? use? SE?

Answer 6

Block P2Y-12 receptor which inhibits ADP-induced activation of platelets

Ticlopidine (rarely used-SE), clopidogrel (major agent), prasugrel, ticagrelor

Long half life, no reversing agent

Used for unstable angina, MI, percutaneous coronary intervention, secondary stroke prophylaxis, periph vasc dis

Synergy with aspirin

SE=bleeding, thrombotic thrombocytopenic purpura (TTP- dangerous), neutropenia

Question 7

What are the anticoagulant?

Answer 7

Older Meds:
Heparin
Warfarin

Newer meds:
LMW heparins
Factor Xa inhibitors
Direct thrombin inhibitors

Question 8

What is rivaroxaban?

Answer 8

Oral Factor Xa inhibitor

VTE (venous thromboembolism) prophylaxis, stroke prevention in non-valvular Afib, VTE treatment

Question 9

What is apixaban?

Answer 9

Treat non-valvular Afib

Problematic in renal dysfunciton bc renally excreted

Question 10

What are the direct thrombin inhibitors?

Answer 10

Block thrombin, more potent than heparin

Includes: Argatroban (small molecule blocker of thrombin, problematic in liver disease), bivalirudin=angiomax (unstable angina/angioplasty), desirudin (VTE prophylaxis), Dabigatran=Pradaxa (oral direct thrombin inhibitor- lots of press, no DDI/food, bleeding possible– stroke prevention in nonvalvular AFib)

Question 11

Warfarin?

Answer 11

Inhibits Vitamin K dependent carboxylase activity by preventing reduction of Vitamin K

Doesn’t affect proteins already synthesized

Multiple DDI’s

Antidote = Vitamin K

Question 12

What is thrombolytic therapy?

Answer 12

Lysing clots that have already formed

Problem: doesn’t discrimiate between therapeutic and pathologic thrombosis –> increased risk of hemorrhage compared with other antithrombotic therapties

Only therapy that prevents tissue death in acute aterial thrombosis (in MI and stroke– more important in stroke!)

Lyses hemostatic plugs everywhere –> SE= bleeding, esp CNS

Question 13

What are the 3 classes of thrombolytic therapy?

Answer 13

Streptokinase: binds plasminogen, activates a second plasminogen molecule to plasmin

Urokinase: activates plasminogen directly

TIssue plasminogen activator: activates plasminogen directly