Pharmacotherapy of Haemostasis and Thrombosis Flashcards
In the platelet ativation and adhesion pathway, what is the role of the receptor GP 1b and Von Willebrand factor?
- GP1b receptor on platelets
- Von Willebrand factor (vWF) binds to collagen
- vWF then binds to GP1b
In the platelet ativation and adhesion pathway, what is the role of the receptor GP2b3a?
- GP2b3a is present on platelets
- binds to fibrinogen
- fibrinogen becomes fibrin
In the platelet ativation and adhesion pathway, what is the role of the receptor Tx receptor on platelets?
- activates platelets and leads to adhesion
In the platelet ativation and adhesion pathway, what is the role of the receptor P2Y12 receptor on platelets?
- activates platelets and adhesion of platlets
If this common drug is given to children as it can cause Reyes syndrome, which is brain and liver damage. What is the drug that causes this if given to children?
- aspirin
- DO NOT GIVE TO CHILDREN
How does aspirin inhibit platelet activation?
- inhibits cyclo-oxygenase (COX-1)
- inhibits conversion of Arachidonic acid to Thromboxane A2
- receptor Tx on platelets is then not activated
- platelets are then not activated
In addition to inhibiting COX-1, what else can higher doses of aspriin inhibit?
- prostocyclin
- prostocyclin normally inhibits platelet activation
Is the inhibition of COX-1 by aspirin permanent or reversible?
- permanent
Why can a low dose of aspirin inhibit COX-1, but not prostocyclin?
- platelets cannot produce more COX-1
- prostocyclin is produced by epithelial cells that can reproduce it
Does aspirin improve all arterial disease?
- yes, used all the time as its cheap
- IHD (MI, angina)
- Cerebrovascular disease
- Peripheral vascular disease
What is the action of clopidogrel that is used to inhibit platelet activation?
- bind with P2Y12 receptor
- inhibits platelet activation
What is one of the main drugs used in patients with peripheral artery disease?
- clopidogral
Warfarin is an oral anticoagulant. How does it affect the coagulation cascade?
- 1972 was era of diSCo
- inhibits factors 10, 9, 7 and 2
- inhibits anti-coagulant proteins S and C
Why is Warfarin not used routinely?
- small therapeutic window
- lots of interactions - alcohol, vitamin K, drugs
- inhibits anti-coagulant proteins S and C
How is Warfarin monitored?
- prothrombin time (PT)
- international normalized ratio (INR)
- normally 2-3 time slower than normal
What 2 cases is warfarin still the maion drug of choice?
- mechanical heart valves
- mitral stenosis with atrial fibrilation
What are the most common side effects of warfarin?
- bleeding
- teratogenic - causes birth defects
- warfarin induced skin necrosis
What are direct acting oral anticoagulants (DOAC) medication?
- oral drugs acting directly on the clotting pathway
Which direct acting oral anticoagulants (DOACs) drug acts on factor Xa (10a) in the coagulation cascade?
- RivaroXAban
- we know this as it contains factor Xa (10a) in the name
The second direct acting oral anticoagulants (DOAC) is called Dabigitran. What is its mechanism of action on the coagulation cascade?
- inhibition of thrombin
- converts fibrinogen to fibrin
What are the 3 cardiac conditions conditions where direct acting oral anticoagulants (DOACs) are routinely used?
- DVT
- PE
- AF
What is heparin?
- anticoagulant (blood thinner) that prevents the formation of blood clots
- the name heparin comes from where is was found - liver = hepatic
What is the mechanims of action of heparin, and what factors in the coagulation cascade does it affect?
- binds to anti-thrombin III and activates it
- IX, VII, II, X, XI, XII
- 9, 7, 7, 10, 11, 12
- 2+7=9….10, 111, 12
How is heparin efficacy measured?
- activated partial thromboplastin time (APTT)
What is unfractionated heparin?
- physiological heparin
- contains high and low molecular weight heparin
What are some of the common problems with unfractionated heparin?
- variable efficacy
- variable dose response
- can cause bleeding
What is fractionated heparin?
- unfractioned heparin that has been spun
- high molecular weight heparins removed
Is fractionated or unfractionated heparin used more commonly?
- fractionated
- better efficacy
What are some common areterial diseases that fractionated heparin is used to treat?
- MI (think blood to pass a thrombus)
- PE (think blood to pass embolism)
- AF (reduce risk of clot in arrythmias)
- VTE (reduce risk of venous thromboembolism)
What are the 2 fractionated drugs that we need to know?
- Enoxaparin and Tinzaparin
- both end in aparin
What is one of the most dangerous problems in patients who are taking direct acting oral anticoagulants and have a major bleed?
- there is no antidote, so difficult to stop bleeding
When would we tend to use unfractionated heparin instead of the more efficous fractionated heparin?
- in patients with chronic kidney disease
What is the major side effect of heparin, other than bleeding?
- Heparin-induced thrombocytopenia (HIT)
Heparin-induced thrombocytopenia (HIT) is a potentially dangerous side effect of heparin. What can HIT cause?
- heparin dependent IgG antibodies bind to heparin/platelet factor 4 complexes and activate platelets
- this causes a hypercoagulable state
- platelet numbers drop
- can cause skin necrosis
Haemophilia is an inability to form blood clots and then bleed to death. What is the most common treatment for Haemophilia?
- recombinant DNA to produce clotting factors
Von Willebrand disease is an inability to form blood clots and then bleed to death. What is the most common treatment for Von Willebrand disease?
- Desmopressin (DDAVP) - increases synthesis/release of vWF
- Anti-fibrinolytics - reduces thrombus breakdown
- Plasma products- replaces vWF and Factor VIII
What factors in the coagulation cascade are vitamin K dependent?
- X (10), IX (9), VII (7) and II (2)
- anticoagulant proteins S and C
- 1972 was the era of diSCo
