Thrombolytic agents Flashcards Preview

Pharm block 4 hemostasis and cardiac > Thrombolytic agents > Flashcards

Flashcards in Thrombolytic agents Deck (27)
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1

Physiologic Activators of the fibrinolytic system

t-PA I - single chain tissue plasminogen activator
Urokinase
Factor XIIa

2

Physiologic Inhibitors of the fibrinolytic system

* PAI-1 (Rapid acting plasminogen activator inhibitor)
Thrombin activatable fibrinolytic inhibitor (TAFI)
* α2-antiplasmin
α2-Macroglobulin

(inhibit plasmin from digesting fibrin)

3

how does α2-antiplasmin have its effects?

α2-antiplasmin complexes with plasmin blocking its active site

4

Plasminogen (Pro-fibrinolysin)

Zymogenic form of the active enzyme plasmin
2 types glu-plasminogen and lys-plasminogen

5

Plasmin (Fibrinolysin)

Active protease capable of digesting both fibrinogen and fibrin.

6

fibrin is formed by

thrombin acting on fibrinogen

7

fibrin is stabilized by

factor XIIIa

8

does plasmin act on stabilized or non-stabilized fibrin?

stabilized

9

D-Dimers

Fragments DDE,YD/DY and YYDD are formed by the action
of plasmin on polymerized fibrin monomers (clots).

10

Factors Which Promote Fibrinolysis

**Plasminogen incorporation into thrombus via fibrin binding
Clot retraction
Local release of t-PA by endothelial cells
**Binding of t-PA to fibrin
Enhanced t-PA or UK activity in the presence of fibrin
Protection of bound plasmin from antiplasmin

11

Factors Which Limit Fibrinolysis

* Fibrin crosslinking by Factor XIIIa
* Binding of α2-antiplasmin to fibrin
Low ratio of endothelial surface to thrombus volume in large vessels
Efficient inhibition of free plasmin by antiplasmin
Antiplasmin impairs plasmin binding to fibrin

12

effects of thrombolytic agents

* Reduction in thrombus size (thrombolytic)
* Reduction of fibrinogen levels
* Increase in fibrinogen and fibrin degradation products
Antiplatelet activators

13

most thrombolytic agents act by

activating plasminogen

14

Clinically Approved Thrombolytic Agents

Urokinase
Streptokinase
Recombinant tissue plasminogen activators (t-PA)

15

Recombinant tissue plasminogen activators available examples (3)

• Alteplase (Recombinant form of Human t-Pa, most used)
• Reteplase (Mutant nonglycosylated form of human t-Pa, more fibrin specific), longer half life
• Tenecteplase (Mutant form of human t-Pa with longer half life), high fibrin specificity.

16

other thrombolytic agents - not used in US

Single chain pro urokinase (Pro-UK, SCU-PA) (under development)
Plasmin (under development)

17

which thrombolytic agent has the most specificity?

t-PA more targeted to the clot (may have less bleeding associated as well)

18

biologic changed that occur after administering a thrombolytic agent

• Circulating plasminogen activator
• Plasminogen converted to plasmin
• Antiplasmin complexes with and inhibits plasmin
• Free plasmin
• Plasmin degradation of fibrinogen
• Degradation of other plasma clotting factors
• Hypocoagulable state

19

what is a side effect of thrombolytic agents and what causes it

systemic lytic state- degradation of plasma fibrinogen by circulating plasmin

20

what is a complication of thrombolytic agents and what causes it

bleeding - degredation of fibrin in hemostatic plugs (possibly also the hypocoagulable state)

21

Clinical Usage of Thrombolytic Agents

MI- due to a thrombus in the coronary vessels
or acute occlusion of coronary after leading to a fibrin-rich clot formation (may lead to an MI)

Peripheral Arterial Occlusion

DVT (localized or systemic treatment)

Pulmonary Embolism (streptokinase and urokinase only)

thrombotic stroke

catheter clearence

22

what factor may lead to decreased affectiveness of thrombolytic agents

Time- the older the clot the less susceptible it is to the lytic action of thrombolytic agents

23

Complications of Thrombolytic Therapy

Bleeding
Re-occlusion
Stroke
Others

24

Absolute Contraindications of Thrombolytic Therapy

Intracranial bleeding
Massive hemorrhage

25

Drug Interactions with Thrombolytic Agents

Antiplatelet Drugs
Heparin
Dextrans

26

Pharmacologic Antagonists for Thrombolytic Agents

• EACA (Epsilon-amino caproic acid)
• Tranexemic Acid (Trans-4-Aminoethylcyclohexane 1-Carboxylic Acid)
• Aprotonin (Trasylol)

can be used if there is too much bleeding due to thrombolytic use

27

DEFIBRINOGENATING ENZYMES can be found where

snake venom - digest fibrinogen