W3: Pharmtx- Drugs affecting Haemostasis Flashcards
- what is colour of venous blood vs normal blood?
- difference btw adult vs babies blood vol
- number of coagulation factors in blood
- whats a factor?
- fibronogen is factor #?
factor= enzymes= breakdown
- Fibrinogen= f1 even though it comes’ last’. world is topsy turvey
How is this relevant?
- gum disease
- crown preps
- daily intake of warfarin or aspirin
aspirin: headaches (more so ibuprofen), blood thinner (not really thinning blood…)
Haemostasis and Thrombosis
- diff types of thrombus
- whats a moving clot?
- what is thrombosis?
- what is DVT?
- ps and erthythrocytes
- clot in arterial system= white thrombus made of ps
- venous clot = red thrombus
Thrombosis
- embolus
- blob/clot could detach and form an embolus, forms in leg= pulmonary embolism
- fibrin, what is it?
- how is it broken down
- which type of medications target it?
Revisiting sites of action of antithrombotics (anticoagulants and
antiplatelets), and thrombolytics (fibrinolytics
anticoagulants target -> fibrin (from fibrinogen)= end point of mesh
- fibrin insoluble strand
- br8ks down via plasminogen
Formation of a thrombus
- what are the main factors involved in clot?
rupture/ stimulus, activate (I/E pw)
10 -> 10a
Thrombin (2a) -> 2
Fibrinogen and fibrin
‘10 to 5’ main part of the story:
F10 (inactive and inactive form)
F2: thrombin
Fibrinogen to fibrin (insol fibre wraps RBC to form thrombus)
EXTRA
Blood coagulation Qs
Formation of a thrombus via platelets
LHS= platelet reaction
rupture
3 As: initial act, adhesion on endothelial, aggreg of ps to make clot
Platelet aggregation mechanisms
+ oral antiplatelet treatments
- whats a PAR?
- what is point of bunch of proteins? and what are their types?
looking at a platelet
- blood vessel with endothelial lining
- collagen with VWFactor
= agents promote p to stick
- GP= glycoprotein:L sugar coated protein
- aspirin blocks COX 1-> TA2, then G protein coupled receptor
thrombin acts thru PAR 4 (protease activated receptor) (Thromboxane P receptors)
- receptor has to broken down b4 it gets activated
- throbin (akak F2) activate PAR
ADP receptor
- P2Y: purinergic receptor, stands for purine.
5HT
- G protein R
POINT
plateletes has bunch of proteins: thromboxine, ADP promoting p aggreg and adhesion.
Qs about Platelets
How do blood thinners work?
- types of thinners
- vit K importance
- Coumadin sig
- new blood thinners MOA
- dont thin blood
- stop clotting by either target coag cascade or activation of platelets
- imp bc if venous clot (red)= anticoag
- arterial thrombus= go with antiplatelets
- Vit K needed to make clotting factors
- Coumadin (capital= trade), generic is Warfarin
- new thinners= block Xa (they affect higher up chain)
Name injectable Anticoags and uses:
Anticoagulants: Injectable (parenteral)
- heparin
- direct TI: target F2 and F10, used for venous embolism, in stroke and MI
balance of thrombin and antithrombin + importance
what is antithrombin?
- where is it made?
- why do we need it?
- what does it target?
Which meds target antithrombin?
what is unwanted affect?
ATIII = affects 10a and 2a
- thrombin, injure= clot, then in body want liquid
heparin= potentiate antithrombin
- importance to monitor, clotting time, how fast clot forms to determine herparin (APTT)
- unwanted effect of anticoagulant: stop clots= extra bleeding. Low platelet level.easy bruising.
abnormal bleeding
Mechanism of Action of Heparins:
Potentiation of the Action of Antithrombin (AT III)
- what 2 factors are inhibited?
heparin binds to 2 inactivated factors (Antithrombin and 2a and 10a)= shows not binding, bit complex. low molecular weight formation
potentiating
Name some Anticoagulants: Oral
exotic agents
Importance of vitamin K (VK):
- why must we need Vit K?
What factor does it form?
How is vit K ‘active’? - Warfarin inhibits what?
- in formation of factors, we need things like (see image) for it to work
- W inhibit K enzyme
Mechanism of Action of Warfarin:
ox-> red form. Warfarin inhibiting enzyme.
basically W= anti K
Oral Anticoagulants: Non-VKAs
non vitamin K antagonist
direct inhibit 2a 10a, faster MOA, more used than warfarin
Antiplatelet drugs
- target Receptors: P2Y antagonists (clopidegral), cyclooxyrgenase, inhibit glycoprotein siting on antips
- dealing with white p thrombus
Synthesis of prostacyclin (PGI2)and thromboxane A2
arachadoinic cascade
block formation of pgs and thromboxane
thromboxane A2 (pro aggreg subs)
Where are glycoproteins expressed?
- recap antip MOA:
- how does main meds work?
- increase expression of receptors
Pharmacology of aspirin as an anti-platelet drug
Anticoagulants and antiplatelets – done!)
Now, thrombolytics (fibrinolytics)
why small dose aspirin?
is it antcoag/antip?
What breaks down fibrin?
What is given after a MI?
- Aspirin binds irreversible
- last long so small dose
- antiplatelet
baby aspirin vs bypass
lots of anticoag= long bleeding, may need to adjust meds b4 being treated…
- quad bypass= stent in 4 arteries,
- bypass vs aspirin= similar
aspirin = better option
LO
