22 - Anticoagulants Flashcards
What two things are needed to control bleeding?
Haemostatic platelet plug and fibrin mesh
How do anticoagulant drugs work and what are some examples?
They prevent thrombus formation and the thrombus growing
What is the mechanism of action of heparin
Enhances Antithrombin III activity via unique pentasaccharide sequence
Deactivates thrombin, Factor Xa, IXa
Antithrombin III is usually made in mast cells and vascular endothelium
What are the two different types of heparin and how are they administered?
Given parenterally (sub cut/IV) as poor GI absorption
- Low molecular weight heparin (only subcut - enzymatically made from UFH)
- Unfractionated heparin (IV for continuous or subcut)
Apart from inactivating thrombin, what other clotting factors does heparin inhibit?
- Deactivates factor Xa, XIIa, XIa and IXa
What are the differences between UFH and LMWH in terms of their action on thrombin and ATIII?
- LMWH only deactivates Xa
- UFH deactivates Xa and Thrombin
Compare and contrast UFH and LMWH based on the following factors:
- Dose-response
- Bio-availability
- Action
- Administration
- Initiation
LMWH used more!!! less monitoring needed
What are some of the characteristics of unfractionated heparin?
- Fast onset
- Short half life so need IV bolus
- Unpredictable
- SC if prophylaxis
- Needs to bind ATIII and IIa to inhibit thrombin but only need ATIII binding with Xa inhibition
Which heparin needs monitoring and why?
Unfractionated with APTT test as affecting intrinsic pathway
What are some of the characteristics of low molecular weight heparin?
- More predictable as higher bioavailability and does not bind to endothelial cells, plasma proteins and macrophages as not long enough
- Longer half life
- Given subcut
- Only inhibits Xa
What are some examples of LMWH’s?
- Dalteparin
- Enoxaparin
- Fondaparinux (synthetic so cheaper and good for veggies)
What are some indications for heparin use?
- Prevention of venous thromboembolism before surgery or for immobile patients (LMWH)
- DVT/PE give LMWH before warfarin to achieve loading dose
- Acute coronary syndromes use LMWH
- Pregnancy instead if warfarin as too large to cross placenta but monitor carefully
What are some adverse drug reactions to heparin?
- Bruising/bleeding intracranially, at site of injection, GI, epistaxis and if old, renally/hepatically impaired or carcinoma, at great risk of bleeding
- Heparin induced thrombocytopenia (more common in UFH)
- Hyperkalaemia due to inhibition of aldosterone sedcretion as acts on mineralcorticoid receptors
- Osteoporosis with long term use and in pregnancy, more common in UFH
What is heparin induced thrombocytopenia?
Autoimmune response up to 2 weeks after initiation of heparin
- Antibodies to heparin platelet factor 4 so depletion of platelets
- Paradoxically lead to more thrombosis as more platelets activated by damaged endothelium
How are the effects of heparin reversed? (e.g if administered too much so bleeding risk or allergy risk)
Protamine Sulphate
- Forms inactive irreversible complex with heparin causing it to disocciate from ATIII. Cationic peptide that binds to heparin forming inactive ion pair
- Given IV
- Greater effect with UFH, no effect on fonaparinux