Anti-platelets

Question 1

Anti-platelets

Answer 1

Aspirin, GP IIB/IIIA receptor blocker, clopdidogrel/ticlopidine, dipyridamole

Question 2

MoA of aspirin

Answer 2

Inhibits COx, prevents arachidonic acid –> PG G2

Prevents formation of Thromboxane A2 –> anti-platelet effect [IRREVERSIBLE]

Question 3

SE of aspirin

Answer 3

Gastric upset & ulcers, increased bleeding risk

Question 4

PK of aspirin

Answer 4

DoA 7-10d (lifespan of platelets + irreversible effect)

Question 5

Use of aspirin

Answer 5

Decrease incidence of recurrent MI, post-MI mortality

Question 6

MoA of GP IIb/IIIa receptor blocker

Answer 6

Displace fibrinogen from binding to GP IIb/IIIa receptor –> prevents further platelet cross-linking & thrombosis

Question 7

Example of GP IIb/IIIa receptor Blocker

Answer 7

Abiciximab — mAb directed against receptor complex –> REVERSIBLY inhibits binding of fibrinogen & ligands to complex

Question 8

MoA of clopidogrel/ticlopidine

Answer 8

Blocks ADP from binding to receptor –> inhibits platelet aggregation

Question 9

MoA of dipyridamole

Answer 9

Inhibit PDE –> inhibits aggregation

Question 10

Anti-coagulants

Answer 10

Antithrombin III, heparin, warfarin

Question 11

ATIII

Answer 11

Endogenous anticlotting protein

Inactivates clotting factor proteases (2a,9a,10a) –> prevents coagulation cascade

Question 12

MoA of heparin

Answer 12

Active heparin binds to ATIII --> conformational change that exposes binding site on ATIII --> rapid interaction with proteases (2a,9a,10a)
Inhibits thrombin (F2a): need to bind with ATIII, F2a
Inhibit 10a: need to bind to ATIII

Question 13

What does LWMH acct on?

Answer 13

LWMH only increases action of ATIII on F10a

Question 14

Is heparin safe to use in pregnancy?

Answer 14

Yes

Question 15

SE of heparin

Answer 15

Haemorrhage (stop Tx, add protamin sulfate to inactive heparin)
Thrombosis, thrombocytopenia (d/t IgG binding to platelet factor 4 & heparin –> activation of platelets –> pro-thrombotic state)

Question 16

MoA of warfarin

Answer 16

Vitamin K reducatase inhibitor –> prevents formation of reduced VitaK –> no carboxylation of glutamate residues = no Factor 2,7,9,10

Question 17

Can warfarin be used in pregnancy?

Answer 17

No

Can cause foetal haemorrhagic disorder, affect foetal proteins in blood & bone

Question 18

SE of warfarin

Answer 18

Increased bleeding risk

Question 19

PK of warfarin

Answer 19

Metabolized by CYP450
Potential DDI with CYP inducers (phenytoin, carbamazepine, barbituates), CYP inhibitors (amiodarone, cimetidine, verapamil)

Question 20

Thrombolytics

Answer 20

Tissue plasminogen activator (tPA, alteplase)

Streptokinase/urokinase/anistroplase

Question 21

MoA of tPA

Answer 21

Activates plasminogen –> start of fibrinolysis

Question 22

MoA of streptokinase

Answer 22

Promotes formation of plasmin from plasminogen –> plasmin exerts thrombolytic action

Question 23

Use of thrombolytics

Answer 23

Emergency treatment of coronary artery thrombosis

Used within 4.5h after stroke

Question 24

SE of thrombolytics

Answer 24

Increased bleeding risk

Question 25

Contraindication of throbolytics

Answer 25

Healing wounds, pregnancy