Antiplatelets, Anticoagulants & Thrombolysis

Question 1

How do antiplatelet agents exert their effects?

Answer 1

Inhibit platelet aggregation

Question 2

What is an example of a cyclo-oxygenase inhibitor?

Answer 2

Aspirin

Question 3

How does aspirin work as an antiplatelet?

Answer 3

Inhibits COX-1 therefore inhibits platelet aggregation
This action occurs at a v low non-analgesic dose
Prolongs bleeding time => haemorrhagic stroke, GI bleeds

Question 4

What are indications for aspirin?

Answer 4

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

Question 5

What are examples of P2Y12/ADP receptor antagonists?

Answer 5

Clopidogrel
Prasugrel
Ticagrelor

Question 6

What are the effects of clopidogrel?

Answer 6

Reduces morbidity and mortality after a thromboembolic stroke
Reduces secondary events post MI
Used as prophylaxis in pts intolerant to aspirin

Question 7

How to P2612/ADP receptor antagonists work?

Answer 7

Inhibit binding of ADP to P2Y12 receptors

Therefore inhibits activation of GPIIb/IIIa receptors

Question 8

What are examples of glycoprotein IIb/IIIa inhibitors?

Answer 8

Abciximab
Tirofiban
Eptifibatide

Question 9

How do GP IIb/IIIa inhibitors exert their effects?

Answer 9

Abciximab - irreversibly blocks GP IIb/IIIa receptors, prevents fibrinogen binding => reduction in aggregation

Eptifibatide - synthetic peptide that binds reversibly

Tirofiban - non peptide reversible antagonist

Question 10

What is a side effect of glycoprotein IIa/IIIb inhibitors?

Answer 10

Thrombocytopenia

Therefore requires platelet count after a few hours

Question 11

What is an example of a phosphodiesterase inhibitor?

Answer 11

Dipyridamole

Question 12

What are some actions of dipyridamole?

Answer 12

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

Question 13

What are some side effects of phosphodiesterase inhibitors?

Answer 13

Flushing and headache

Hypersensitivity

Question 14

What are some indications for phosphodiesterase inhibitors?

Answer 14

Secondary prevention of ischaemic stroke and TIA

Prophylaxis of thromboembolism w/ prosthetic heart valves

Question 15

What are some examples of fibrinolytic agents?

Answer 15

Streptokinase
Alteplase
Reteplase
Tenecteplase

Question 16

How does streptokinase work as a fibrinolytic?

Answer 16

Activates plasminogen => converts to plasma => fibrinolysis of clots

Question 17

When are fibrinolytics given?

Answer 17

Acute MI

DVT, PE

Question 18

What is the action of anticoagulant drugs?

Answer 18

Prevents thrombus formation and thrombus growing

Question 19

What is an example of a vitamin K antagonist?

Answer 19

Warfarin

Question 20

How does warfarin act as an anticoagulant?

Answer 20

Inhibits production of Vit K dependent clotting factors

Stops conversion of Vit K to active reduced form

Question 21

What is warfarin used for?

Answer 21

DVT/PE prophylaxis and treatment
AF w/ risk of stroke
Protein S and C deficiency
Post orthopaedic surgery

Question 22

Why is there a delayed onset of action with warfarin?

Answer 22

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

Question 23

What is an ADR of warfarin?

Answer 23

Bleeding

Antidote is vitamin K, prothrombin or fresh frozen plasma

Question 24

What are some DDIs of warfarin?

Answer 24

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

Question 25

What is are examples of parenteral anticoagulants?

Answer 25

Unfractionated heparin

Low molecular weight heparin

Question 26

How does unfractionated heparin act as an anticoagulant?

Answer 26

Binds to antithrombin => conformational change => increased activity
Also inactivates some clotting factors

Question 27

What are some examples of LMWH?

Answer 27

Bempiparin
Dalteparin
Enoxaparin

Question 28

How do LMWHs act?

Answer 28

Targets factor Xa

Doesn’t inactivate thrombin
More predictable dose response, as it doesn’t bind to endothelial cells, plasma proteins and macrophages

Question 29

What is heparin used for?

Answer 29

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

Question 30

What are some ADRs of heparin?

Answer 30

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

Question 31

How can the effects of heparin be reversed?

Answer 31

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

Question 32

What are the effects of fondaparinux?

Answer 32

Selectively inhibits Xa by binding to ATIII

Question 33

What are examples of direct acting oral anticoagulants?

Answer 33

Apixaban
Edoxaban
Rivaroxaban

Question 34

How do DOACs act?

Answer 34

Inhibits free and bound Xa

Doesn’t effect thrombin

Question 35

What are examples of direct thrombin inhibitors?

Answer 35

Argatroban

Dabigartran