fibrinolytic

Question 1

what is the main function of the fibrinolytic pathway?

Answer 1

increase the conversion of plasminogen to plasmin which degrades fibrin and dissolves the clot

Question 2

what is t-PA?

Answer 2

tissue plasminogen activator
a serine protease that can activate plasminogen to plasmin
inhibited by PAI-1 and PAI-2

Question 3

what are the indications for thrombolytic therapy?

Answer 3

acute myocardial infarction
acute ischemic thrombotic stroke
pulmonary embolism

Question 4

when should thrombolytic therapy be employed?

Answer 4

initiate as soon as possible after onset of AMI

Question 5

when should thrombolytic therapy be initiated with acute ischemic thrombotic stroke?

Answer 5

only within 3 hours after onset and exclusion of intracranial hemorrhage

Question 6

what is the main function of drugs to tx acute MI?

Answer 6

prevent restenosis (narrowing of stented artery) by inhibiting smooth muscle cell proliferation
increases risk of subsequent thrombosis tho

Question 7

what drugs are t-PAs?

Answer 7

alteplase (activase)
reteplase (retevase)
tenecteplase (TNKase)

Question 8

what is the main difference of reteplase in comparison to other t-PAs?

Answer 8

lacks fibrin binding domain so less fibrin-specific
more potent though with faster onset

Question 9

what are anti-fibrinolytic agents used for?

Answer 9

to stop bleeding caused by thrombolytic drugs

Question 10

what drugs are anti-fibrinolytic agents?

Answer 10

tranexamic acid (10x more potent)
aminocaproic acid
lysine

Question 11

what are the clinical uses of anti-fibrinolytic agents?

Answer 11

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

Question 12

what are the major risks associated with anti-fibrinolytic agents?

Answer 12

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

Question 13

what is the half life of aminocapronic acid?

Answer 13

2 hrs IV and 2 hrs oral

Question 14

what is the half life of tranexamic acid?

Answer 14

2 hrs IV
11 hrs oral

Question 15

what is the MOA for anti-fibrinolytic agents?

Answer 15

prevent binding of plasminogen and plasmin to fibrin
spares clots and prevents hemorrhage

Question 16

how does aminocaproic acid differ from lysine?

Answer 16

analogue without a second NH2 group

Question 17

how does tranexamic acid differ from lysine?

Answer 17

analogue with a 6 ring structure
becomes 10x more potent than EACA

Question 18

what do the mutations on tenecteplase give rise to?

Answer 18

increased half life
reduced inhibition by PAI
enhanced activity at thrombi

Question 19

where are the point mutations of tenecteplase?

Answer 19

start of kringle 1/2 and start of protease domain

Question 20

hwo does alteplase compare in terms of selectivity?

Answer 20

binds fibrin
works on the fibrin clot

Question 21

how does reteplase compare in terms of selectivity?

Answer 21

more potent with faster onset
lacks fibrin binding domain so less fibrin specific
works in plasma