Fibrinolytics

Question 1

What are the synthetic tPA drugs?

Answer 1

Alteplase
Reteplase
Tenecteplase

shortest to longest duration <5 minutes thru 20-25 minutes.

Question 2

What is alteplase

Answer 2

recombinant tPA -activates plasminogen to plasmin

Question 3

What is Reteplase

Answer 3

Recombinant tPA with the fibrin binding domain removed.

Acts more rapidly and lasts about 15 minutes instead of 5.

Question 4

What is Tenecteplase

Answer 4

Recombinant tPA that is PAI-1 resistant.

Question 5

What are the antidotes to the fibrinolytics

Answer 5

Aminocaproic Acid - competitive inhibitor of plasminogen activator proteins. Competes with plasminogen for binding site.

Aprotinin - plasmin, trypsin, kallekrein, general serine protease inhibitor

Fresh Frozen Plasma
Cryoprecipitate
Coagulation factor concentrates

Question 6

What are the non-tPA fibrinolytics?

Answer 6

Streptokinase
Anistreplase
Staphylokinase
Urokinase

Question 7

What is Anistreplase

Answer 7

A bound complex of streptokinase and plasminogen together

Also acts to activate endogenous plasminogen

half life 1.5 hours

Question 8

What is the half life of streptokiase?

Answer 8

30 minutes. given i.v. (all thrombolytics are given i.v.)

Question 9

What is Staphylokinase

Answer 9

Same effects and mech as streptokinase but slightly less effective and less antigenic

Question 10

What is Urokinase

Answer 10

Human enzyme isolated from urine.

Not immunogenic,

half life 15 minutes.

Question 11

What are the indications for fibrinolytic treatment

Answer 11

Acute MI if PCI is unnavailable within 2 hours

Severe DVT of PE with hemodynamic instability

Ischemic stroke, within 4.5 hours of symptom onset.

Question 12

Contraindications for fibrinolytis

Answer 12

Any active internal bleeds

Significant trauma or surgery within the past 10 days, especially head trauma

Significant GI or Cranial bleeding within the past 3 months

Severe hypertension

Aortic dissection or Aortic pericarditis.

Question 13

Fibrinolytic SEs

Answer 13

Bleeding, especially intracranial bleeding.

• Bleeding complications as high as 15% of patients.
• Lethal bleeding in 0.5%

Allergic and anaphylactic reactions possible to Streptokinase, Anistreplase, and Staphylokinase

Question 14

Drugs used in bleeding disorders

Answer 14

Local:

• Vasoconstrictors, Epinephrine, NE, Desmopressin
• Collagen, Gelatin, Fibrin meshes
• Injections/sclerotherapy to vericose veins/hemorrhoids

Systemic:

• Vitamin K orally
• Fresh Frozen plasma
• Cryoprecipitates of concentrated cotting factors
• Aminocaproid acid and its derivatives
  antidote for fibrinolytics

Question 15

When is amiocaproic acid used?

Answer 15

In fibrinolytic overdose

Prophylactic therapy for hemophilia

Post-surgical bleeding

Prophylaxis for intracranial aneurysm rebleeding.

Question 16

What is Aprotinin

Answer 16

bovine pancreatic trypsin inhibitor (BPTI),

an antifibrinolytic molecule that inhibits trypsin and related proteolytic enzymes.

inhibits plasmin, trypsin, kallikrein, chymotrypsin

only administered i.v.

Question 17

What is Aprotinin’s indications

SEs

Answer 17

Bleeding from thrombolytics

Used in devices for extracorporeal circulation

SEs:
Allergic, anaphylctic reactions

Reversible liver damage and decreased kidney function.