Antiplatelet, Anticoagulants And Thrombolysis Flashcards
Why does the inhibition last for 7-10 days?
Hydrolysed in the liver to?
ADRs?
Why may they lack efficacy in some people?
Indications?
Platelets are non-nucleated and therefore will not form more TXA2.
Salicylic acid
Haemorrhagic stroke
Peptic ulcer
COX-1 polymorphisms
Secondary preventions of stroke, TIA, ACS, MI stable angina and peripheral vascular disease.
Post PCI and stent to reduce ischaemic complicaitons.
Name 3 ADP receptor antagonists.
Which ones are irreversible inhibitors?
MOA.
Why should loading dose be used with clopidogrel?
Which ones are pro-drugs and which one is an active drug?
Clopidogrel
Prasugrel
Ticagrelor
CPT
CP
Inhibit P2Y12 receptor - inhibiting activation of GPIIa/IIIb
Because it has a slow onset of action otherwise.
CP = pro T= active
Name three GPIIa/IIIb inhibitors.
Why does abciximab have the greatest chance of bleeding associated with it?
Route of admin?
Why does abciximab also have a longer predicted action relative to its short half life?
Abciximab
Tirofiban
Eptifibatide
Because it binds irreversibly (leading to a more than 80% reduction in platelet binding)
IVI bolus
Because of slow dissociation
Pyramidole mechanism of action x2.
ADRs.
Why headaches?
Uses.
Inhibits PDE - increased cAMP and cGMP levels -> reducing intracellular calcium -> inhibition GPIIb/IIIa receptor expression.
Inhibits cellular reuptake of adenosine -> increased plasma adenosine -> inhibits platelet aggregation via A2 receptors.
Flushing
Headaches
Hypersensitivity
Vasodilator effect also.
Secondary prevention of ischaemic stroke and TIAs
Adjunct to oral anticoagulants for TE prophylaxis following valve replacement.
Which factors are independant to the extrinsic and intrinsic pathway?
Which factors start the intrinsic and extrinsic pathways?
8 9 11 12
3 7
12 and 7 respectively
Heparin.
Give two places it is endogenously produced.
Give some factors inactivated by heparin-ATIII complex.
Why do they show poor GI absorption?
Difference in route of admin compared to LMWHs.
Which have a slower onset of action?
What is used to monitor?
Comment on bioavailability.
Mast cells and endothelium vascular
IXa Xa XIa XIIa and thrombin
Large and negatively charged molecules.
LMWHs - SC
Heparin - IV
LMWH
PTT
Bioavailability 90% LMWHs - heparin - unpredictable.
Name 5 LMWHS.
Why less likely to cause thrombocytopenia?
Dalteparin Enoxaparin Tinzaparin Reviparin Bempiparin
Only Xa inactivated.
LMWH use.
Why used in pregnancy?
Another use for heparins.
ADRs.
DVT PE and AF - before warfarin
Do not cross the placenta.
ACS - reducing recurrence or extension of CA thrombosis post MI and NSTEMI
Bruising Bleeding (intracranial, epistaxis) HIT Osteoporosis (UFH risk up) Hypersensitivity Hyperaldosteronism
What is used for perioperative prophylaxis of VTE?
Pathophysiology behind HIT.
LMWHs for a few days.
Antibodies formed against heparin-PAF4 complex - on platelet surface - induction of platelet activation occur due to cross linking of FcepsilonII receptors
Pro-thrombotic even though platelets are depleted because platelet activation is occurring.
How does protamine sulfate work?
Compare effect on LMWH and fondaparinux.
Where might it be used clinically?
Highly cationic therefore forms a stable ion pair with heparin causing it to dissociate away from ATIII.
LMWH - less effect
No effect - fondaparinux
Antidote following surgeries where large doses of it may be required.
MOA fondaparinux.
Upside compared to UFH?
Name 3 direct Xa inhibitors.
Name 2 direct thrombin inhibitors.
Collectively known as?
Why can direct thrombin inhibitors be used in HIT?
Binds to ATIII to selectively inhibit Xa
Less monitoring needed
Apixaban
Rivaroxaban
Edoxaban
Argatroban
Dabigatran
DOACs or NOACs
Do not bind to platelet factor 4.
Warfarin.
MOA.
What is factor II?
What type of isomerism?
Why is there a delay in the onset of action?
Protein binding?
Inhibits vitamin K epoxide reductase means there is not enough vitamin K hydroquinone form for gamma glutamyl carboxylase to use to carboxylate glutamic acid residues on cfs II VII IX and X meaning they are not activated.
Prothrombin
Enantiomers - racemic mixture.
Circulating active clotting factors present for several days - must be replaced by their inactived forms.
Highly protein bound.
Uses of warfarin.
Give some variables that should be considered when giving warfarin.
Why is PT used as opposed to APPT?
Give three antidotes.
DVT prophylaxis and treatment PE prophylaxis and treatment Atrial fibrilation with high risk of stroke Protein C and S deficiency After Orthopaedic surgery
CYP2C0
Vit K intake
Coagulation proteins
Because factor VII is the most sensitive to vitamin K deficiency.
Vitamin K1
Prothrombin complex
Fresh frozen plasma
Why is warfarin not contraindicated in breast feeding mothers?
Why are cephalosporins a DDI?
Why should you avoid drink?
What should INR be in DVT PE and AF treatment?
Recurrent DVT or PE
Mechanical prosthetic valves
What does an INR in normal people of above three significantly increase the risk of?
Since babies are naturally Vit K deficient - they are prescribed Vit K
Reduce vitamins K production by gut microbiota
Inhibition of CYP 2C9.
- 5+/- 0.5
- 5 +/- 0.5
Sub-dural haemorrage
Give some fibrinolytic agents.
If bleeding is induced by these what can be administered?
Two drawbacks to streptokinase?
Streptokinase Urokinase Alteplase Reteplase Tenecteplase
Tranexamic acid
Antigenic
Less clot selective and therefore more likely to cause bleeds.
