Antithrombotic Drugs Flashcards
How are anticoagulants given; the predominant way and other ways
Direct Oral Anticoagulants (DOACs) 90%
Also orally and heparin
What is the name + role of a predominant oral anticoagulant
Prevents unwanted thrombosis
Warfarin - Vitamin K Antagonist
(Wisconsin Alumni Research Foundation -arin)
Mechanism of Warfarin
Vitamin K normally supports production of prothrombin and coagulation factors as it is involved in post-ribosomal carboxylation of their glu acid residues, needed to function
warfarin blocks Vit K reductase, needed for Vit K to act as a co-factor
What can warfarin be used for
Patients with replaced heart valves
Atrial Fibrillation
Pulmonary Embolism
DVT
What is the time frame for warfarin to act (Broadly)
Several days
How is warfarin’s therapeutic window found
Patient’s INR (prothrombin time) is measured; target dose adjusted accordingly
What must be kept in mind during warfarin prescription
Drug interactions and Side Effects
Main side effect of warfarin
Bleeding as a result of lack of coagulation
What are some injectable anticoagulants
Unfractionated heparin or LMWHs [Low molecular weight heparin] (e.g. enoxaparin, tinzaparin)
Mechanism of injectable anticoagulants
Activating antithrombin III; antithrombin inactivates some clotting factors and thrombin by complexing with serine protease of some coagulation factors
Discuss the time frame of heparin to kick in
Immediate action (used whilst warfarin takes effect)
Direct Oral Anticoagulants (DOAC)
Like warfarin but:
Far less interactions
Less bleeding than warfarin
Does not require monitoring
Rapid
Mechanisms such as acting as thrombin inhibitors or activated factor X inhibitors
Seemingly equally effective as warfarin in treating AF
What is the benefit of Warfarin over DOACs
DOACs cannot be easily reversed (until recently; done with mAB which can reverse it) while warfarin can just be reversed using Vit K
DOACs vs Warfarin in principle
DOACs act directly on the coagulation cascade while warfarin acts on the factors
Prostacyclin
A member of the prostaglandin group of lipid molecules made in epithelia of blood vessel walls
It is a vasodilator and anti-platelet agent; increases cAMP
(PGI2)
Thromboxane
Txa2
Released by platelets when platelets adhere, causing further adhesion and decrease of cAMP
Nitric Oxide in Blood
Blood vessels release NO to keep blood pressure down;
it also prevents both platelet adhesion and aggregation through increasing platelet cGMP
Aspirin
Low dose anti platelet drug
Used to proevent MI in patients who have previously had an MI;
Inhibits cyclooxygenase
Mechanism of Aspirin
Aspirin irreversibly inhibits cyclo-oxygenase, reducing thromboxane
Why does aspirin greatly favour PGI2 production over TXA2
Patient takes aspirin; it hits both enzymes
Endothelia are nucleated though, which produce more mRNA, so they can re-produce COX within 2 hours
Platelets are anuclear, so they cannot produce COX and thus thromboxane (for 7 days till new ones are synthesised)
Clopidogrel
Drug that inhibits ADP binding to the receptors, reducing expression of glycoprotein IIb/IIIa
Good in blocking cerebrovascular disease
(Think of it in the class of an ADP blocker)
Abciximab
Monoclonal Antibody that binds to glycoprotein IIb/IIIa, inhibting its actions, given to patients undergoing angioplasty; only use once
Thrombolytics
Used in breakdown of clots
Alteplase
Dissolves clot and restores blood flow
Primary treatment of stroke and pulmonary embolism
What has replaced the use of thrombolytics in myocardial infarctions
Angioplasties with a stent
Contra-indications of Alteplase
Hemmoragic strokes
Post-surgery
