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Pharm block 4 hemostasis and cardiac > Thrombolytic agents > Flashcards

Thrombolytic agents Flashcards

1
Q

Physiologic Activators of the fibrinolytic system

A

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

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2
Q

Physiologic Inhibitors of the fibrinolytic system

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

(inhibit plasmin from digesting fibrin)

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3
Q

how does α2-antiplasmin have its effects?

A

α2-antiplasmin complexes with plasmin blocking its active site

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4
Q

Plasminogen (Pro-fibrinolysin)

A

Zymogenic form of the active enzyme plasmin

2 types glu-plasminogen and lys-plasminogen

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5
Q

Plasmin (Fibrinolysin)

A

Active protease capable of digesting both fibrinogen and fibrin.

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6
Q

fibrin is formed by

A

thrombin acting on fibrinogen

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7
Q

fibrin is stabilized by

A

factor XIIIa

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8
Q

does plasmin act on stabilized or non-stabilized fibrin?

A

stabilized

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9
Q

D-Dimers

A

Fragments DDE,YD/DY and YYDD are formed by the action

of plasmin on polymerized fibrin monomers (clots).

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10
Q

Factors Which Promote Fibrinolysis

A

**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

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11
Q

Factors Which Limit Fibrinolysis

A
  • 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
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12
Q

effects of thrombolytic agents

A
  • Reduction in thrombus size (thrombolytic)
  • Reduction of fibrinogen levels
  • Increase in fibrinogen and fibrin degradation products
    Antiplatelet activators
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13
Q

most thrombolytic agents act by

A

activating plasminogen

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14
Q

Clinically Approved Thrombolytic Agents

A

Urokinase
Streptokinase
Recombinant tissue plasminogen activators (t-PA)

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15
Q

Recombinant tissue plasminogen activators available examples (3)

A
  • 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.
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16
Q

other thrombolytic agents - not used in US

A

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

17
Q

which thrombolytic agent has the most specificity?

A

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

18
Q

biologic changed that occur after administering a thrombolytic agent

A
  • 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
Q

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

A

systemic lytic state- degradation of plasma fibrinogen by circulating plasmin

20
Q

what is a complication of thrombolytic agents and what causes it

A

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

21
Q

Clinical Usage of Thrombolytic Agents

A

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
Q

what factor may lead to decreased affectiveness of thrombolytic agents

A

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

23
Q

Complications of Thrombolytic Therapy

A

Bleeding
Re-occlusion
Stroke
Others

24
Q

Absolute Contraindications of Thrombolytic Therapy

A

Intracranial bleeding

Massive hemorrhage

25
Q

Drug Interactions with Thrombolytic Agents

A

Antiplatelet Drugs
Heparin
Dextrans

26
Q

Pharmacologic Antagonists for Thrombolytic Agents

A
  • 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
Q

DEFIBRINOGENATING ENZYMES can be found where

A

snake venom - digest fibrinogen

Pharm block 4 hemostasis and cardiac (12 decks)

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