Anticoagulants Flashcards
How does aspirin work?
At low doses it:
- Inhibits COX1
- COX1 is needed to form thromboxane A2 (TXA2)
- Reduction of TXA2 inhibits platelet aggregation (irreversible)
Indications of aspirin?
- prevention of stroke, TIA and ACS
- post Percutaneous Coronary Intervention and stent
- prevention of MI in stable angina
Contraindications for aspirin?
active peptic ulcers, bleeding disorders, renal impairment
How do clopidogrel and prasugrel work?
Antiplatelets !!!
binds irreversibly to P2Y12 receptor, inhibiting ADP from binding to it
This inhibits GPIIb/IIIa receptors from being activated.
When do we use P2Y12/ADP receptor antagonists? eg. clopidogrel
post MI, etc.
How does abciximab work?
Antiplatelets !!!!
irreversibly blocks GPIIb/IIIa receptors
This inhibits fibrinogen from binding
This reduces aggregation
It is more completely inhibiting than eg. clopidogrel, as GP2b/3a receptors are found at the end of the pathway.
What is a SE of abciximab?
- huge bleeding risk
- Thrombocytopenia
How does dipyridamole work?
Antiplatelets!!!
phosphodiesterase inhibitor.
prevents cAMP and cGMP degradation
this inhibits expression of GP2b/3a receptors
This reduces aggregation
When is dipyridamole used?
prevents ischaemic stroke and TIA
used as adjunct to oral anticoagulants after valve replacement
Name a fibrinolytic agent “clot buster” and an agent that inhibits fibrinolysis
“clot buster” = streptokinase, alteplase, reteplase
Inhibitor of fibrinolysis = tranexamic acid
How does warfarin work?
Anticoagulant !!!
Inhibits conversion of vit K to active reduced form (inhibits VK epoxide reductase)
Inhibits synthesis of vit K dependent clotting factors
(Prothrombin II, X, IX, VII)
(Delayed onset of action as circulating active clotting factors remain for a while)
when is warfarin used?
DVT/PE prophylaxis and treatment
AF with high stroke risk
mechanical prosthetic valves
following ortho surgery (stasis)
***heparin cover if anticoagulation needed immediately, due to delayed onset of action.
when is warfarin contraindicated?
functional 2C9 polymorphism (CYP2C9 metabolism)
amiodarone, clopidogrel, metronidazole, etc inhibit hepatic metabolism esp CYP2C9
pregnancy (1st and 3rd trimesters)
St Johns wort, barbiturates, etc accelerate warfarin metabolism
How do you stop warfarin?
Reverse by using vitamin K1, prothrombin complex concentrate IV, fresh frozen plasma, and stop warfarin.
How does unfractionated heparin work?
it binds to antithrombin (ATIII) and causes a conformational change
ATIII inactivates thrombin IIa, factor Xa, IXa, XIa and XIIa
(To inhibit IIa, heparin must simultaneously bind ATIII and IIa)
IV infusion or SC as poor GI absorption
How does dalteparin work?
It is a low molecular weight heparin
works same as heparin, but more predictable dose response
(does not bind to endothelial cells, plasma proteins, macrophages)
Less likely to cause thrombocytopenia
Targets Xa specifically.
Does not inactivate thrombin IIa
When are heparins indicated?
DVT, PE, AF
- prior to warfarin as quicker onset prior to warfarin loading
post MI or NSTEMI, Acute Coronary SYndrome
During pregnancy as does not cross placenta
prevention of venous thromboembolism perioperative (LMWH)
When are heparins contraindicated?
hepatic and renal compromise
How do you reverse heparins?
Protamine sulphate dissociates heparin from ATIII
How do apixaban and rivaroxaban work?
Inhibits free Xa and Xa bound to ATIII
(Direct Xa inhibition)
No effect on thrombin IIa
hepatic metabolism, excreted partly by kidneys
How does dabigartran work?
Direct competitive thrombin inhibitor (both circulating and thrombus bound IIa)
