fibrinolytic system

Question 0

explain streptokinase
nature
MOA
pharmacokinetics

Answer 0

streptokinase is a bacterial protein
SK first binds to plasminogen –> conformational change to form active complex

PK

• iv
• beneficial effect additive w aspirin
• first admin: give large dose to overcome antibodies
• but it is total fibrinogen digestion and not just clot specific :(
• actions blocked by AB that appears 4 days aft initial dose
• immunisation and cannot be readministered for nxt 3 years - ineffective

Question 1

explain how fibrinolytic system works

Answer 1

when coagulation cascade is activated, fibrinolytic is set in motion via endogenous plasmingoen activators - tissue-PA, urokinase type plasminogen activator and kallikerin

plasminogen is deposited on fibrin strands within thrombus
plasminogen will be cleaved to plasmin via t-PA. tPA are serine proteasaes and are unstable in circulating blood, diffuses itno thrombus
plasminogen–>plasmin that will hence degrade fibrin strands and lyse the clot

action is localised as plasminogen activators are mainly effective on plasminogen adhered/adsorbed to fibrin clot

fibrinolytic drugs/thrombolytic drugs
all drugs are administered IV to degrade existing thrombus in individual w MI, stroke or PE
all drugs are ENZYMES that converts plasminogen-> plasmin strands within thrombus

Question 2

recombinant t-PA 
give 2 examples
MOA
OK
SEs

Answer 2

alteplase
reteplase

more active on fibrin-bound-plasminogen > free plasminogen in plasma
hence clot specific

recombinant tPA is not antigenic and can be used in patients likely to have AB to SK

alteplase: short half life and hence given IV
retaplase - longer half life hence bolus administration

SE:
hypersensitivity reaction to SK and tPA
bleeding