Anti-platelets Flashcards
Anti-platelets
Aspirin, GP IIB/IIIA receptor blocker, clopdidogrel/ticlopidine, dipyridamole
MoA of aspirin
Inhibits COx, prevents arachidonic acid –> PG G2
Prevents formation of Thromboxane A2 –> anti-platelet effect [IRREVERSIBLE]
SE of aspirin
Gastric upset & ulcers, increased bleeding risk
PK of aspirin
DoA 7-10d (lifespan of platelets + irreversible effect)
Use of aspirin
Decrease incidence of recurrent MI, post-MI mortality
MoA of GP IIb/IIIa receptor blocker
Displace fibrinogen from binding to GP IIb/IIIa receptor –> prevents further platelet cross-linking & thrombosis
Example of GP IIb/IIIa receptor Blocker
Abiciximab — mAb directed against receptor complex –> REVERSIBLY inhibits binding of fibrinogen & ligands to complex
MoA of clopidogrel/ticlopidine
Blocks ADP from binding to receptor –> inhibits platelet aggregation
MoA of dipyridamole
Inhibit PDE –> inhibits aggregation
Anti-coagulants
Antithrombin III, heparin, warfarin
ATIII
Endogenous anticlotting protein
Inactivates clotting factor proteases (2a,9a,10a) –> prevents coagulation cascade
MoA of heparin
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
What does LWMH acct on?
LWMH only increases action of ATIII on F10a
Is heparin safe to use in pregnancy?
Yes
SE of heparin
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)
MoA of warfarin
Vitamin K reducatase inhibitor –> prevents formation of reduced VitaK –> no carboxylation of glutamate residues = no Factor 2,7,9,10
Can warfarin be used in pregnancy?
No
Can cause foetal haemorrhagic disorder, affect foetal proteins in blood & bone
SE of warfarin
Increased bleeding risk
PK of warfarin
Metabolized by CYP450
Potential DDI with CYP inducers (phenytoin, carbamazepine, barbituates), CYP inhibitors (amiodarone, cimetidine, verapamil)
Thrombolytics
Tissue plasminogen activator (tPA, alteplase)
Streptokinase/urokinase/anistroplase
MoA of tPA
Activates plasminogen –> start of fibrinolysis
MoA of streptokinase
Promotes formation of plasmin from plasminogen –> plasmin exerts thrombolytic action
Use of thrombolytics
Emergency treatment of coronary artery thrombosis
Used within 4.5h after stroke
SE of thrombolytics
Increased bleeding risk
Contraindication of throbolytics
Healing wounds, pregnancy
