Pharmacology- clots Flashcards
what is haemostasis
arrest of blood loss from a damaged vessel
what is exposed when a vascular wall is damaged
collagen and tissue factor (thromboplastin)
what happens in primary haemostasis
platelet adhesion, activation and aggregation (by fibrinogen)
local vasoconstriction
what is the final step of haemostasis
activation of blood clotting and the formation of a stable clot by fibrin enmeshing platelets
what do activated platelets release
thromboxane A2 which causes mediator release (serotonin (5-HT) and adenosine diphosphate (ADP)) and vasoconstriction
what does ADP do
binds to platelet GPCR purine receptors causing;
- further platelet activation
- formation of soft plug
- initiate coagulation of blood and solid clot formation
what converts fibrinogen to fibrin in order to form a solid clot
thrombin
what is thrombosis
a haematological plug in the absence of bleeding
describe aterial thrombus
(white) mainly platelets in fibrin mesh
where do aterial embolis often lodge
in brain
what is the primary treatment of arterial thrombus
antiplatelet drugs (block aggregation and activation of platelets)
describe the components of a venous thrombus
(red) fibrin rich
where do venous embolis often lodge
in lung
what is the primary treatment of venous thrombus
anticoagulants
name six anticoagulants
warfarin, rivaroxiban, heparin, LMWH, dabigatran, fondaparinux
what is the role of vitamin K
mediates enzymes producing clotting factors II, VII, IX and X (precursors of active clotting factors e.g. thrombin= IIa)
what do all anticoagulants carry a risk of
haemorrhage
how does warfarin work
competes with vit k to bind, preventing production of active clotting factors and coagulation
how is warfarin administered
orally
what is the half life of warfarin and why is that important
usually 40 hours (variable)- if patient needs op
how is the overdosage of warfarin treated
with administration of Vit K
why does warfarin have a low therapeutic index
as hard to balance anticoagulant effect and haemorrhage. use complicated by delay to maximal effects and several medical and environmental influences
what can increase risk of haemorrhage with warfarin
liver disease (decreased clotting factors), high metabolic rate (increased clearance of clotting factors), drug interactions
what factors can lessen warfarin action
physiological state (pregnancy, hypothyroidism), vitamin K consumption, drug interactions
what is antithrombin III
an important inhibitor of coagulation which neutralise all clotting factors (a.k.a serine protease factors) in the coagulation cascade
what binds to antithrombin III to increase its affinity for clotting factors
heparin- greatly increases rate if inactivation
name two low molecular weight heparins
enoxaprin and dalteparin
how do LMWH’s work
inhibit factor Xa (not thrombin)
how is heparin administered
IV or SC
how are LMWHs administered
SC
why is heparin preferred in renal failure
as LMWH is eliminated via renal excretion
what are the adverse effects of heparin and LMWH
haemorrhage (and rarely…), osteoporosis, hypersensitivity reactions
how do orally active inhibitors work
inhibit thrombin or factor Xa
what is TXA2
thromboxane A2, is released from activated platelets
how does aspirin work
irreversibly blocks cycloxygenase in platelets, preventing TXA2 synthesis
what is the main adverse effect of
gastrointestinal bleeding and ulceration
what is clopidogrel and how/ when is it used
anti-platelet drug, orally, in patients with aspirin intolerance
what happens when clopidogrel and aspirin are combined
have a synergistic effect
what is tirofiban and how/ why is it administered
antiplatelet drug, IV, prevents MI in patients with high risk unstable angina
what is the role of the fibrinolytic cascade
opposes the coagulation cascade
when are fibrinolytics used
to reopen occluded arteries in acute MIs or stroke (less frequently venous thrombosis/ PE)
how are fibrinolytics administered
IV, and have beneficial effect with aspirin
what is streptokinase and why is it used
fibrinolytic drug, reduces mortality in MI
what are alteplase and duteplase
recombinant tissue plasminogen activators, fibrinolytic drugs
how are alteplase and duteplase administered and what is their main side effect
iv infusion, haemorrhage- controlled by tranexamic acid which inhibits plasminogen activation
