drugs and stroke Flashcards
what is haemostasis?
balance between normal blood functioning and preventing blood loss
where is haemostasis most effective?
small blood vessels (arterioles), capillaries and venules
what is haemostasis a complex interaction between?
vasoconstriction
platelets
coagulation (clotting factors + inhibitors)fibrinolysis
name the two types of blood clotting and the substances involved in each
venous - clotting factors activated (inherited/acquired)
arterial - involves platelets
what is a thrombosis?
formation of a thrombus within the vessel
what can cause a thrombus?
pooling of blood in veins - DVT
damaged vessels - atheromatous plaques
describe the formation of a thrombus
fibrin framework - platelets and other blood cells become trapped
attached to vessel wall - leads to impeded blood flow and reduced profusion of tissue
what is the difference between a venous and arterial thrombosis?
venous - coagulation major factor
arterial - platelet aggregation major factor - coagulation also involved
what is an embolus?
fragment or whole thrombus which detaches from wall of blood vessel
what happens when an embolus occurs?
fragment or whole thrombus travels through blood vessels- blocks small vessels in pulmonary, cardiac, CNS circulation
what results from a embolus?
pulmonary embolism (PE) myocardial infarction (MI) stroke
what drugs are used to modify coagulation?
heparins (anticoagulants)
is heparin present in the body naturally?
yes - present in lungs, liver and mast cells
what impact does the molecular weight of the heparin have?
heparin - standard, unfractioned (natural form)
low MW heparin - more effective, less side effects
both activate anti-thrombin
name three low MW heparins
enoxaparin
dalteparin
tinemaparin
describe the action of heparin
-activates anti-thrombin (AT)-activated AT forms complexes with clotting factors: thrombin, factors Xa (+ FIXa/XIa) causing them to be inactivated-heparin increase rate of complex formation
what are some of the disadvantages to using heparin?
poorly absorbed orally - must be give IV or Sub-cut
risk of haemorrhage
what would be done if haemorrhage occurred in a patient using heparin?
mild: cease admin
severe: give protamine sulphate (forms complex with heparin - inactivating)
name a commonly used oral anticoagulant
warfarin
how does warfarin work?
-related to structure of vit. K-antagonises vit K role in formation of various clotting factors (II- prothrombin, VII and IX)-warfarin prevents conversion of these active factors-precursors to these factors are inactive in coagulation
what are the problems associated with warfarin?
slow onset - fully anti-coagulated after 3 daysactivity influenced by vit K - intake, absorption, gut flora
probs with antibiotics
many interactions - foods/drugsrisk of haemorrhage
what is the INR target for recurrent DVT?
3.0 (2.5-3.5)
when taking warfarin haemorrhage is at increased risk, what would you do to reverse the effect of warfarin?
mild: stop admin
severe: vit K, clotting factors, whole blood, fresh frozen plasma
can warfarin be used during pregnancy?
no - teratogen (must be avoided in early pregnancy and ideally throughout)
how can warfarin interact with other drugs?
enzyme induction - eg. carbamazepine
enzyme inhibition - eg. cimetidine
name four thrombin inhibitors
Rivaroxaban (Xarelto)
Dabigatran (Pradaxa)
bivalirudin
lepirudin
what is the target for Rivaroxaban?
inhibitor of Factor Xa
what is the target for Dabigatran?
thrombin inhibitor
what happens when platelets are activated?
the platelets form ‘legs’ which stick to other platelets
explain the process of platelet aggregation
vessel damaged collagen exposed platelets bind here and are activated increased synthesis of TxA2increased GPIIb/IIIa receptors expression on platelet platelets aggregate
which two substances are produced from an atheromatous plaque by the COX enzyme?
thromboxane A2 (TxA2)- promotes aggregation of platelets by reducing cAMP Prostacyclin (PGI2) - reduces platelet aggregation by increasing cAMP* a balance of both is important
name three targets for affecting platelet activation and aggregation
synthesis of thromboxane A2 cAMP levels in platelets Glycoprotein IIb/IIIa receptors on platelets
What is the action of Aspirin as an antiplatelet drug?
irreversibly blocks platelet COX enzyme - reducing TxA2 synthesis (platelets won’t clump together)
platelets have no nuclei so no new enzyme is synthesised (eg. aggregation reduced)
why is only a low dose of aspirin given as a antiplatelet drug?
low dose (75mg) used to avoid reducing enzyme in endothelium (PGI2)* aspirin alters balance of platelet TxA2 and endothelial PGI2
What is the action of Dipyridamole as an antiplatelet drug?
inhibits phosphodiesterase (PDE) enzyme - prevents breakdown of cAMP in platelets (eg. reduces platelet aggregation)blocks adenosine uptake into platelets, red cells and endothelial cells - inhibits TxA2 synthesis
What is the action of Clopidogrel as an antiplatelet drug?
inhibits glycoprotein IIb/IIIa receptor expression on platelets
inhibits ADP recetors - blocking activation of the glycoprotein IIb/IIIa pathway (this is the final common pathway for platelet aggregation/ important in cross linking platelets and fibrin)
what are thrombolytic agents used for?
dissolve pre-existing clot or thrombus - most effective in acute/emergency situation (within 6hrs of onset)
name four thrombolytic agents
alteplase
reteplase
urokinase
streptokinase
what are the dangers of using thrombolytic agents?
danger of haemorrhage - clotting factors used uprisk of emboli - fragment could split from thrombus
how are thrombolytic agents usually administered and why?
IV or intracoronary admin as fast acting
explain how alteplase works
inside thrombus fibrin strands bound to plasminogen
alteplase binds to this complex and converst inactive plasminogen to active plasmin
plasmin then digests fibrin - thrombus dissolves
