Fibrinolytic Drugs

Question 1

Activated to dissolve the clot when the blood vessel defect has healed

Answer 1

the fibrinolytic pathway

Question 2

Plasmin

Answer 2

proteolytic enzyme that digests fibrin and fibrinogen

Question 3

Plasminogen

Answer 3

anticoagulant protein that circulates in an inactive form; deposited on a growing clot

Question 4

tissue plasminogen activator (t-PA)

Answer 4

cleaves arg-val bond to activate plasminogen to plasmin

Question 5

Plasmin is inactivated by

Answer 5

alpha2-antiplasmin

Question 6

t-PA is inhibited by

Answer 6

PAI-1 and PAI-2

Question 7

Streptokinase forms activator complex with

Answer 7

plasminogen

Question 8

Indications for thrombolytic therapy

Answer 8

acute myocardial infarction, acute ischemic thrombotic stroke, pulmonary embolism

Question 9

Alteplase

Answer 9

recombinant human t-PA; binds fibrin

Question 10

Reteplase

Answer 10

recombinant human t-PA; more potent, faster onset; lacks fibrin binding domain - less fibrin-specific

Question 11

Tenecteplase

Answer 11

recombinant, mutant form of t-PA; longer half life, given by a single IV bolus; more fibrin specific than t-PA

Question 12

What do the mutations in tenecteplase do?

Answer 12

increase half life; reduce inhibition by PAI; enhance activity at thrombi

Question 13

Plasminogen bound to fibrin is selectively activated by

Answer 13

t-PA that is also bound to fibrin

Question 14

adverse effects of t-PA

Answer 14

internal bleeding; superficial or surface bleeding

Question 15

MOA of streptokinase

Answer 15

forms 1:1 complex with plasminogen to produce an active enzyme complex that catalyzes conversion of inactive plasminogen to active plasmin

Question 16

Dosing of streptokinase

Answer 16

given IV in a loading dose to saturate endogenous antibodies against the protein

Question 17

Adverse effects of streptokinase

Answer 17

bleeding; allergic reactions

Question 18

MOA of urokinase (kinlytic)

Answer 18

directly cleaves plasminogen to plasmin; lacks fibrin specificity and can induce a systemic lytic state

Question 19

Clinical indications for urokinase

Answer 19

massive PE

Question 20

Adverse effects of urokinase

Answer 20

bleeding; low incidence of allergic reactions (human protein)

Question 21

Anti-fibrinolytic agents are used to

Answer 21

stop bleeding caused by thrombolytic drugs

Question 22

Anti-fibrinolytic agents

Answer 22

aminocaproic acid, tranexamic acid, lysine

Question 23

MOA of anti-fibrinolytic agents

Answer 23

plasmin binds to fibrin through a lysine binding site to activate fibrinolysis; drugs act as a lysine analog to bind the receptor on plasminogen and plasmin; the result is blockade of plasmin binding to target fibrin

Question 24

Clinical uses of anti-fibrinolytic agents

Answer 24

treat bleeding associated with thrombolytic therapy; adjunct therapy in hemophilia; re-bleeding from intracranial aneurysms

Question 25

Major risks of anti-fibrinolytic agents

Answer 25

intravascular thrombosis as result of fibrinolysis inhibition; thrombi formed during therapy are not easily lysed

Question 26

Tranexamic acid and aminocaproid acid prevent binding of

Answer 26

plasminogen and plasmin to fibrin, sparing clots and preventing hemorrhage