6.2 anti platelets, anticoagulants and thrombolysis Flashcards
(31 cards)
when is venous thrombosis likely to occur and what does it look like?
associated with stasis of blood and/or image to the veins = less likely to see endothelial damage
high red blood cell and fibrin contents low platelet content and evenly distributed
when is arterial thrombosis likely to occur and what does it look like?
usually forms at site of atherosclerosis forming a plaque rupture
lower fibrin content and much higher platelet count
why would the type of thrombus indicate a different treatment?
lower platelet count red venous thrombus = use anticoagulants e.g heparin and warfarin
higher platelet count arterial thrombi = antipatelet and fibrinolytic drugs
how does aspirin work?
it is a COX 1 inhibitor = reduces the amount of thromboxane and thus inhibits platelet aggregation, with irreversible effects
good for platelet rich thrombi e.g arterial thrombi
higher doses will have a counter effect so need to get it right
what are the side effects of aspirin?
bleeding time prolonged e.g haemorrhage stroke and GI bleeding (peptic ulcers)
how do clopidogrel and prasugrel work?
inhibit platelet aggregation as a P2Y/ADP receptor antagonist
reduce morbidity and mortality post thromboembolic stroke
reduce secondary events post MI with asprin
useful in prophylaxis in patients intolerable to aspirin
how does abciximab work?
irreversibly blocks GPIIb/IIIa receptors preventing fibrinogen binding
given IV, also a glycoprotein
how does dipyridamole work?
inhibits cellar reuptake of adenosine = increased plasma adenosine = inhibits platelet aggregation via a2 receptors
will also inhibit photodiesterase = prevent cAMP and cGMP degradation = inhibits GPIIb/IIIa expression
what are the side effects of dipyridamole?
flushing and headache, hypersensitivity
what is the role of plasminogen activators in thrombolysis?
convert plasminogen to plasmin, which helps fibrinolysis of a fibrin clot
what is the role of streptokinase in thrombolysis?
name 2 other drugs which work in the same way as streptokinase.
activates plasminogen
streptokinase similar drugs include:
- alteplase
- reteplase
what is the role of tranexamic acid in thrombolysis?
aids fibrinolysis of the fibrin clot into degradation products
why can’t streptokinase be given repeatedly?
its antigenic aka will trigger an immune response
therefore, given in short infusions and less commonly used than the others
what are anticoagulant drugs?
prevent thrombus formation and thrombus growing
how can vitamin K agonists prevent clotting? give an example
vit K agonists e.g warfarin (half life 36-48hrs)
inhibit production of vit K dependant clotting factor and stops conversion of vitamin k to active reduced form (inhibits reductase)
so, can’t do hepatic synthesis of clotting factors e.g prothrombin and factor 7
when is warfarin used therapeutically?
DVT prophylaxis and treatment PE prophylaxis and treatment AF with high risk of stroke Protein S and C deficiency following orthopaedic surgery (stasis)
what are the properties of warfarin?
slow onset of action = need heparin cover if anticoagulation is needed immediately
good GI absorption and taken orally
highly protein bound (remember displacement issues)
activity highly variable in individuals - monitor INR
what is INR?
An INR test measures how long it takes for your blood to clot. It is primarily used to diagnose unusual bleeding, blood clots, and monitoring people being treated with warfarin (an anti-clotting treatment).
A low INR result means your blood is ‘not thin enough’ or coagulates too easily and puts you at risk of developing a blood clot.
A high INR result means your blood coagulates too slowly and you risk bleeding.
normal INR range = 1-1.5
why should warfarin be watched In pregnancy?
it can cross the placenta
so avoid in
1st trimester - tetrogenic
3rd trimester - brain haemorrhage
what is warfarin response governed by?
CYP2C9,
other drugs,
vit K intake,
coagulation proteins
how should warfarin be monitored?
factor 7 is most sensitive to vit k deficiency so used in prothrombin time - standardised against control plasma = INR test
what is the main ADR of warfarin and how can this be treated?
main ADR
- bleeding
most effective treatment
- antidote of vit k1
- prothrombin complex iv
- fresh frozen plasma
- stop warfarin
what are warfarins main drug-drug interaction ?
- inhibition of hepatic metabolism, especially CYP2C9, amiodarone, clopidogrel, alcohol, quinolone, metronidazole
- inhibit platelet function (no real reaction with aspirin but blood will be extra thin = monitor carefully)
- taken with some antibiotics, will affect vitamin K ability to be eliminated and eliminate gut bacteria
- NSAIDS inhibit vit k absorption and increase INR, also displace warfarin from plasma albumin
- acceleration of warfarin metabolism e.g barbiturates, rifampicin phenytoin, St johns wort. will all decrease INR
give an example of a paraenteral anticoagulant
e.g heparins
they inhibit the action of coagulation factors
heparin produced naturally in mast cells and vascular endothelium and extracted for clinical age
