antiplatelets and fibrinolytics

Question 1

4 steps for atherosclerosis formation

Answer 1

1. Endothelial cell dysfunctional damage (age, cholesterol, smoking, etc)
   
   2. LDLs infiltrate and become oxidised
   3. Atherosclerotic plaque formation - immune response
   4. Plaque breaks down - thrombosis

Question 2

what are the main roles of platelets

Answer 2

circulatory integrity
essential for haemostasis, healing and inflammation
secretion of granule contents
aggregation

Question 3

how are platelets activated

Answer 3

activate when exposed to damage, collagen and von Willebrand factor
can also be activated by thromboxane A2 and ADP

Question 4

how is platelet adhesion and aggregation stopped

Answer 4

nitric oxide - from endothelial cells - and prostacyclin inhibit activation and aggregation

Question 5

what is the role of antiplatelet drugs

Answer 5

decrease platelet aggregation and inhibits thrombus formation in arterial circulation

Question 6

what are some examples of antiplatelet drugs

Answer 6

aspirin, thienopyridines, ticagrelor, glycoprotein IIb/IIa inhibitors

Question 7

how does aspirin work as an antiplatelet drug

Answer 7

inhibits COX 1 in platelets, cannot be resynthesized so reduces thromboxane A2 production

Question 8

what is the role of COX1 in coagulation

Answer 8

found on platelets - causes aggregation

Question 9

what is the role of COX 2 in coagulation

Answer 9

found on epithelial cells causes platelet aggregation, but can resynthesise COX

Question 10

how do Thienopyridines work as antiplatelets

Answer 10

clopidogrel and prasugrel pro-drugs, Inhibit ADP-induced aggregation and antagonises platelet P2Y12 receptor

Question 11

how does ticagrelor work as an antiplatelets

Answer 11

nucleoside analogue, § Blocks P2Y12 ADP receptors on platelets - allosteric

Question 12

how do Glycoprotein IIb/IIIa inhibitors work as antiplatelets

Answer 12

§ Inhibit all pathways of platelet aggregation by binding to Glycoprotein IIb/IIIa inhibitors - blocks fibrinogen binding

Question 13

when would Glycoprotein IIb/IIIa inhibitors be used in clinic

Answer 13

with heparin and aspirin for prevention of complications in patients undergoing percutaneous coronary intervention or in early MI prevention in unstable angina/NSTEMI

Question 14

what is the role of the fibrinolytic system

Answer 14

to remove and resolve clots

Question 15

how does the fibrinolytic system remove clots

Answer 15

plasmin formation and activation - potent proteolytic enzyme

Question 16

how is plasmin formed and activated

Answer 16

formed by plasminogen and activated by tissue plasmin activators/urokinase/kallikrein

Question 17

which drugs stimulate the fibrinolytic system

Answer 17

streptokinase
reteplase
alteplase
urokinase

Question 18

how does streptokinase work

Answer 18

converts plasminogen to plasmin, hepatically cleared, forms antigenic antibodies but can only be used once a year

Question 19

how does reteplase and tenecteplase work

Answer 19

recombinant human tPA More active on fibrin bound plasminogen than plasma plasminogen (clot selective)
□ Not antigenic
□ Reteplase within 12hr, Tenecteplase within 6hr

Question 20

how does alteplase work

Answer 20

□ First line for acute ischaemic stroke, DVT, PE
□ More active on fibrin bound plasminogen than plasma plasminogen (clot selective)
□ Not antigenic
□ Given within 9-12 hr

Question 21

how does urokinase work

Answer 21

○ Not selective for clot-bound fibrin so less useful