Anticoagulants Flashcards
(43 cards)
Anticoagulant drugs prevent thrombus formation and growth.
List 3 natural inhibitors of the clotting cascade
- Antithrombin III (especially with regards to Heparin’s action)
- Protein C
- Protein S
Which ion is a cofactor for the clotting cascade?
What can be given with a blood transfusion to prevent clotting?
- Calcium
- EDTA (Chelates Ca, preventing it from being used to clot)
Most heparins are sourced from animals
Compare the Heparins: UFH and LMWH in terms of size
How do Heparins work?
Unfractionated Heparins;
- Large
Low Molecular Weight Heparins;
- Smaller
- Heparins work by enhancing Antithrombin III activity (in vivo AND in vitro)
In what form are Heparin preparations?
Prepared in Units (IU) per ml
List the targets of the following Heparins;
- UFH
- LMWH
- Fondaparinux (A synthetic LMWH)
UFH;
- Acts on Thombin IIa and Xa mainly (also on 12a, 11a, 9a)
LMWH;
- Acts on Xa
Fondaparinux;
- Acts on Xa
Describe the Pharmacodynamics of UFH
- Fast onset of action
- 30 mins half life at Low doses
- 2 hours half life at high doses
- This difference in half life results in mixed elimination so is unpredictable elimination kinetics
Describe the Administration of UFH
- Typically, IV Bolus followed by Infusion
- Can be given Subcutaneously for prophylaxis, but low bioavailability
Describe the mechanism of action of UFH
- Binds to ATIII causing conformational change and increased activity
- To catalyse Thrombin IIa inhibition, UFH must bind to ATIII AND IIa
- To catalyse Xa inhibition, UFH only need to bind to ATIII
What kind of drug are Dalteparin and Enoxaparin?
State their administration, half life and bioavailability
- LMWHs
- Almost always given SC (can be IV) as high bioavailability
- Half life of 2hrs plus
(Slower onset of action)
Why are LMWHs more predictable than UFHs?
LMWHs are smaller and don’t bind to Endothelial cells (partial elimination of UFH here)
How do LMWHs work?
Enhance ATIII activity to inhibit Xa
Not long enough to inactivate Thrombin IIa
Compare Fondaparinux with the natural LMWHs
Fondaparinux;
- Same mechanism of action and administration route
- Longer half life of 18 hours
List 4 indications for use of Heparins
- Venous thromboembolism prevention (before/ after operations as patients have been immobile)
- During pregnancy (do not cross placenta)
- Treating + secondary prevention of DVT and PE (prior to DOACs)
- Acute Coronary Syndrome/ ACS (NSTEMI), in the short term
List 4 ADRs of Heparins
- Bruising + bleeding (Intracranial, Site of injection, GI, Nose)
- Heparin Induced Thrombocytopenia, HIT (Autoimmune response, more common with UFH)
- Hyperkalaemia (Inhibition of Aldosterone secretion)
- Osteoporosis (Rare, long term use, higher risk with UFH, more common in pregnancy)
Describe Heparin Induce Thrombocytopenia (HIT)
- Antibodies to Heparin-Platelet factor IV complex
- Platelets depleted
- IN SOME, can lead to Thrombosis as more platelets activated by endothelial damage
List 2 contraindications of Heparins
- Clotting disorders
- Renal impairment (LMWH + Fondaparinux)
List DDIs of Heparins
- Other antithrombotics
- ACEi/ ARBs + Spirionalctone (Increased risk of Hyperkalaemia)
Which form of Heparin requires more monitoring?
Against what value is the dose titrated?
- UFH
- APTT (Intrinsic pathway: XII, XI, IX, VIII + Common)
Suggest a drug used for Heparin Reversal Therapy
How does it work?
- Protamine Sulphate (given IV)
- Irreversibly forms inactive complex with Heparin, dissociating it from ATIII
Compare the effects of Protamine Sulphate on;
- UFH
- LMWH
- Fondaparinux
Protamine Sulphate;
- Greater effect on UFH
- Weaker effect on LMWH
- No effect on Fondaparinux
Name a Vitamin-K Antagonist
How do these drugs work as anticoagulants?
- Warfarin
- Inhibit conversion of Vit-K to active form via Competitive Inhibition of VKOR
- Thus, inhibited activation of Vit-K dependent clotting factors (7,9,10,2)
How is Vitamin K involved in production of Factors II, VII, IX and X
Hepatic synthesis of the clotting factors requires Vit-K as a cofactor for activation
Why does Warfarin have a delayed onset of action?
How can we speed this up?
- Already circulating active clotting factors are present for days
- Active factors can be cleared and replaced with non-carboxylated forms
State the half life of Warfarin
36 to 48 hours (some variation)
