Thrombolytic Drugs and Drugs used in bleeding

Question 1

Finally the last set of drugs in drugs used to reduce clotting are the Thrombolytics (fibrinolytic) drugs. What are some features?

Answer 1

Ineffective against pre-existing clots
–used to lyse blood clots and restore patency of vessel
Thrombolytic agents act by converting the inactive zymogen plasminogen to the active protease plasmin
Can lead to hemorrhage to due to effect on both pathological and physiological clots
Reduce mortality of acute MI and are used in situations in which PCI (angioplasty ) is not available

Question 2

Now lets talk about the various thrombolytics. First is streptokinase, how does this drug work?

Answer 2

Combines with plasminogen
–catalyzes the conversion of plasminogen into plasma
–catalyzes the degradation of fibrinogen, factor V and VII.
Use:
acute MI, acute PE, arterial thrombosis and occluded access shunts

Question 3

The next thrombolytic is urokinase. How does this drug work?

Answer 3

Synthesize by the kidney
—converts plasminogen into plasmin
Use:
lysis of PE

Question 4

The next three throbolytic drugs, Alteplase, Reteplase and Tenecteplase. What is their MOA?

Answer 4

Tissue Plasminogen Activator (t-PA)
–serine protease produced by endothelial cells
Activates plasminogen bound to fibrin in a thrombus or hemostatic plug
t-PA is fibrin selective
During therapeutic infusions of t-Pa, however, the higher concentrations of t-Pa may lead to activation of circulating plasminogen, leading to hemorrhage

Question 5

Lets discuss each individual t-Pa drug. First is Alteplase, what are features of this drug?

Answer 5

Recombinant t-Pa
Use:
–management of acute myocardial infarction and acute ischemic stroke
given within 4.5 hours of the onset of stroke like symptoms

Question 6

Second is Reteplase, what are features of this drug?

Answer 6

Recombinant t-Pa
–longer half life so given as a double bolus
Use:
–management of acute MI

Question 7

Third is Tenecteplase, what are features of this drug?

Answer 7

Mutant t-Pa
–longer half life, so given as a bolus
Use:
Acute MI

Question 8

Finally some clinical pharmacology. What is the prevention and treatment for a venous thrombosis?

Answer 8

Prevention:
–primary prevention reduces incidence of clots
—SC administration of low dose unfractionated heparin, LMW heparin or fondaparinux provides effective prophylaxis. Warfarin is also effective but needs to be monitored
Tx:
–UFH or LMWH for the first 5-7 days with an overlap with warfarin. warfarin is then continued for 3-6 months
–prego women get heparin

Question 9

What is the prevention and treatment for an arterial thrombosis?

Answer 9

Tx with platelet inhibiting drugs such as aspirin and clopidogrel is indicated in patients with transient ischemic attacks/strokes, or unstable angina and acute MI
In angina and MI these drugs are often used in conjunction with beta blocks and other drugs

Question 10

Lastly lets touch on drugs used to treat bleeding. First are your plasminogen activation inhibitors, Aminocaproic Acid and Tranexamic Acid. What are the features of these drugs?

Answer 10

Inhibitors of fibrinolysis 
--inhibit plasminogen activation 
Uses:
--adjunctive therapy in hemophilia and for bleeding form fibrinolytic therapy 
Adverse:
--intravascular thrombosis

Question 11

Next set of drugs for treatment of bleeding is Protamine Sulfate. What are the features of this drug?

Answer 11

Chemical agonist of heparin
Use:
–given IV to reverse the effects of heparin in situations of life threatening hemorrhage or great heparin excess
–active against UFH and partially reverse anticoagulant effects of LMWHs
–Inactive against Fondaparinux

Question 12

Next drug for the treatment of bleeding is vitamin K. What are features of this drug?

Answer 12

Correct bleeding tendency or hemorrhage associated with its deficiency
Uses:
–drug induced hypothrombinemia: oral and parenteral forms and effect is complete by 24 hours when treating depression of prothrombin activity by excess warfarin or vit K deficiency
–prevention of vitamin K deficiency bleeding in newborns: all babies are deficient and need vit K administered at birth

Question 13

If immediate hemostasis is required, what should you give?

Answer 13

Fresh-frozen plasma

Question 14

Finally the last drug for use in bleeding is Plasma Fractions, what are the features of this drug?

Answer 14

Deficiencies in plasma coagulation factors can cause bleeding
–factor VIII deficiency (classic hemophilia or hemophilia A) and factor IX deficiency (Christmas disease or hemophilia B)