Block V, Antithrombotic & Thrombolytic Agents

Front 1

Draw the Coagulation Cascade

Back 1

Front 2

Name the Antithrombotic Agents
(Anticoagulants)

Back 2

Heparin
Low-molecular weight heparins
-Enoxaparin
-Dalteparin
-Tinzaparin
Fondaparinux
Warfarin (Coumadin)
Direct thrombin inhibitors
-Bivalirdin
-Lepirudin
-Argatroban

Front 3

Name the Antithrombotic Agents
(Antiplatelets)

Back 3

Aspirin
Dipyridamole
Thienopyridines
-Ticlopidine
-Clopidogrel
-Prasugrel
Glycoprotein IIb/IIIa Inhibitors
-Abciximab
-Eptifibatide
-Tirofiban

Front 4

Thrombolytic Agents

Back 4

Streptokinase
Urokinase
Alteplase (tPA)
Reteplase
Tenecteplase

Front 5

Drugs to Treat Bleeding

Back 5

Aminocaproic Acid
Protemine Sulfate
Vitamin K

Front 6

MOA of Heparin

Back 6

Binds to antithrombin III and catalyzes the inactivation of factors IIa, Xa, IXa, and XIIa.

Factors IIa and Xa most sensitive.

*Ternary complex to inhibit factor IIa (requires 18 saccarides)*

Front 7

Monitor Heparin with:

Back 7

APTT
Therapeutic range or 1.5-2.0 x control.

Front 8

MOA of LWMH

Back 8

Just like heparin, but smaller so less Anti-IIa activity compared to Anti-Xa (2:1 to 4:1)

Front 9

Advantages of LWMH over Heparin

Back 9

-Predictable dose-response anticoagulation
-Increased bioavailability
-Longer duration of action
-Dose-independent clearance
-Decreased incidence of thrombocytopenia
-No laboratory monitoring required

Front 10

Fondaparinux

Back 10

A synthetic pentasaccharide with specific anti-Xa activity (via ATIII)

Front 11

Warfarin

Back 11

Inhibits vitamin K epoxide reductase which results in the loss of carboxylation of factors II, VII, IX, and X so they can't bind Ca++ (only 10-40% as effective)
*Slow onset (5 x 36 hours)

Front 12

How to monitor Warfarin therapy:

Back 12

PT
INR (Normal: .8-1.0, Therapeutic 2.0-3.5)
- If INR >9.0 give vitamin K 2.5-5mg PO (INR should decreas in 6-8 hours, 24-48 hours for full effect).

Front 13

Argatroban

Back 13

Small molecule that directly inhibits trombin
*monitor with aPTT and adjust for liver function
*Used in patients with HIT.

Front 14

Lepirudin and Bivalirudin

Back 14

Directly inhibit all actions of thrombin by binding in 1:1 molar ratio.
*No antidotes
*Monitor with aPTT adjust for kidney disease.

Front 15

Asprin

Back 15

Irreversibly binds to and inactivates COX-1, which prevents production of TXA2
*No effect on activated platelets.

Front 16

Dypyridamole

Back 16

Inhibits phosphodiesterase in platelets
*potentiates de-aggregating effects of prostacyclin.
*Little effect by itself, adjunct to warfarin or aspirin.

Front 17

MOA of Thienopyridines

Back 17

Irreversible inhibition of ADP induced platelet activations.
*All must be activated by CYP450

Front 18

Abciximab

Back 18

Murine monoclonal antibody that inhibits glycoprotein IIb/IIIa
*May cause allergic reactions
*Half life is that of platelets.

Front 19

Tirofiban

Back 19

A non-peptide glycoprotein IIb/IIIa inhibitor.
*Half-life of 90-180 mins

Front 20

Eptifibatide

Back 20

Synthetic cyclic heptapeptide glycoprotein IIb/IIIa inhibitor.
*Half life of 1-2.5 hours.

Front 21

MOA of Glycoprotein IIb/IIIa Inhibitors

Back 21

Block glycoprotein IIb/IIIa from binding fibrinogen.
*Platelet function significantly decreased at 50% blockade
*Still 80% blockade has minimal effect of bleeding time
*>90% blockade gives extremely prolonged bleeding time.

Front 22

Streptokinase

Back 22

Indirect plasminogen activator, converts plasminogen to plasmin.
Low affinity for fibrin (systemic lytic state)
*Can cause allergic reaction*

Front 23

Urokinase

Back 23

Naturally occuring plasminogen activator (Produced by the kidneys)
Directly activates plasminogen.
Less antigenic than streptokinase
Lacks fibrin specificity (Systemic lytic state)

Front 24

Alteplase

Back 24

Tissue-type plasminogen activator
High affinity for fibrin (limits systemic lytic state)

Front 25

Reteplase

Back 25

A deletion mutant variant of tPA that still directly converts plasminogen.

Front 26

Tenecteplase

Back 26

Multiple point mutations of alteplase
*increased resistance to PAIs and longer half life (18-20 mins)
**More fibrin specific that alteplase**

Used for acute myocardial infarction.

Front 27

Aminocaporic Acid

Back 27

Competitive inhibitor of plasminogen activators.

Front 28

Protamine Sulfate

Back 28

Positive charged protein from fish sperm that binds to and inactivated Heparin.

Front 29

Vitamin K

Back 29

Has something to do with Warfarin : )

Front 30

Absolute Contraindication to Thrombolytic Use

Back 30

Any prior intracranial hemorrhage
Known structural cerebral vascular lesion (e.g. arteriovenous malformation)
Known malignant intracranial neoplasm (primary or metastatic)
Ischemic stroke within 3 mo except acute ischemic stroke within 3 hr
Suspected aortic dissection
Active bleeding or bleeding diathesis (excluding menses)
Significant closed-head or facial trauma within 3 mo.

Front 31

Is the intrinsic or extrinsic pathway more important for in vivo coagulation?

Back 31

Extrinsic
*initiated by tissue factor or thromboplastin.