Antiplatelets, Anticoagulants & Thrombolysis Flashcards
How do antiplatelet agents exert their effects?
Inhibit platelet aggregation
What is an example of a cyclo-oxygenase inhibitor?
Aspirin
How does aspirin work as an antiplatelet?
Inhibits COX-1 therefore inhibits platelet aggregation
This action occurs at a v low non-analgesic dose
Prolongs bleeding time => haemorrhagic stroke, GI bleeds
What are indications for aspirin?
Secondary prevention of stroke and TIA
Secondary prevention of ACS
Post PPCI and stent to reduce ischaemic complications
Secondary prevention of MI in stable angina or peripheral vascular disease
Inhibition lasts for life span of platelet, 7-10 days
What are examples of P2Y12/ADP receptor antagonists?
Clopidogrel
Prasugrel
Ticagrelor
What are the effects of clopidogrel?
Reduces morbidity and mortality after a thromboembolic stroke
Reduces secondary events post MI
Used as prophylaxis in pts intolerant to aspirin
How to P2612/ADP receptor antagonists work?
Inhibit binding of ADP to P2Y12 receptors
Therefore inhibits activation of GPIIb/IIIa receptors
What are examples of glycoprotein IIb/IIIa inhibitors?
Abciximab
Tirofiban
Eptifibatide
How do GP IIb/IIIa inhibitors exert their effects?
Abciximab - irreversibly blocks GP IIb/IIIa receptors, prevents fibrinogen binding => reduction in aggregation
Eptifibatide - synthetic peptide that binds reversibly
Tirofiban - non peptide reversible antagonist
What is a side effect of glycoprotein IIa/IIIb inhibitors?
Thrombocytopenia
Therefore requires platelet count after a few hours
What is an example of a phosphodiesterase inhibitor?
Dipyridamole
What are some actions of dipyridamole?
Inhibits cellular re-uptake of adenosine => increased plasma adenosine => inhibits platelet aggregation via A2 receptors
Phosphodiesterase inhibitor therefore prevents cAMP/cGMP degradation => inhibits expression of GP IIb/IIIa
What are some side effects of phosphodiesterase inhibitors?
Flushing and headache
Hypersensitivity
What are some indications for phosphodiesterase inhibitors?
Secondary prevention of ischaemic stroke and TIA
Prophylaxis of thromboembolism w/ prosthetic heart valves
What are some examples of fibrinolytic agents?
Streptokinase
Alteplase
Reteplase
Tenecteplase
How does streptokinase work as a fibrinolytic?
Activates plasminogen => converts to plasma => fibrinolysis of clots
When are fibrinolytics given?
Acute MI
DVT, PE
What is the action of anticoagulant drugs?
Prevents thrombus formation and thrombus growing
What is an example of a vitamin K antagonist?
Warfarin
How does warfarin act as an anticoagulant?
Inhibits production of Vit K dependent clotting factors
Stops conversion of Vit K to active reduced form
What is warfarin used for?
DVT/PE prophylaxis and treatment
AF w/ risk of stroke
Protein S and C deficiency
Post orthopaedic surgery
Why is there a delayed onset of action with warfarin?
Circulating active clotting factors are present for a few days
Must be cleared and replaced w/ non-carboxylated forms
Therefore heparin is required if immediate anticoagulation is needed
What is an ADR of warfarin?
Bleeding
Antidote is vitamin K, prothrombin or fresh frozen plasma
What are some DDIs of warfarin?
Most DDIs increase anticoagulation effect
Inhibition of hepatic metabolism, CYP 2C9; amiodarone, clopidogrel, high EtOH, metronidazole
Inhibit platelet function; aspirin
Elimination of gut bacteria => reduction in Vit K; cephalosporin
Acceleration of warfarin metabolism; St John’s Wort
What is are examples of parenteral anticoagulants?
Unfractionated heparin
Low molecular weight heparin
How does unfractionated heparin act as an anticoagulant?
Binds to antithrombin => conformational change => increased activity
Also inactivates some clotting factors
What are some examples of LMWH?
Bempiparin
Dalteparin
Enoxaparin
How do LMWHs act?
Targets factor Xa
Doesn’t inactivate thrombin
More predictable dose response, as it doesn’t bind to endothelial cells, plasma proteins and macrophages
What is heparin used for?
DVT, PE, AF - quicker onset prior to warfarin loading
ACS
Can be used in pregnancy, as it doesn’t cross the placenta
Prevention of VTE - perioperative prophylaxis
What are some ADRs of heparin?
Bruising and bleeding
Intracranial, site of injection, GI, epistaxis
Elderly or those with carcinoma more at risk
Heparin induced thrombocytopenia
Autoimmune response, antibodies to heparin platelet factor 4 complex => depletion fo platelets
Osteoporosis
Hypersensitivity
How can the effects of heparin be reversed?
Protamine sulphate - dissociates heparin from ATIII
Loss of +ve charge neutralises sulphate
Used as antidote to heparin post surgery where large doses of heparin were used
Greater effect on UFH
What are the effects of fondaparinux?
Selectively inhibits Xa by binding to ATIII
What are examples of direct acting oral anticoagulants?
Apixaban
Edoxaban
Rivaroxaban
How do DOACs act?
Inhibits free and bound Xa
Doesn’t effect thrombin
What are examples of direct thrombin inhibitors?
Argatroban
Dabigartran
