10 Haemostasis and thrombosis Flashcards
(52 cards)
10.01 IRREVERSIBLE COX-1 INHIBITOR
Aspirin - actions
antiplatelet (also analgesic and anti-inflammatory)
10.01 IRREVERSIBLE COX-1 INHIBITOR
Aspirin - MOA
irreversibly inactivates cyclo-oxygenase (COX)-1
alters balance between thromboxane A2 (TXA2) and prostacyclin (PGI2) in the platelet/vascular endothelium axis
10.01 IRREVERSIBLE COX-1 INHIBITOR
Aspirin - abs/distrib/elim
given orally in small doses
excretion in urine, increased if urine is alkalinised
10.01 IRREVERSIBLE COX-1 INHIBITOR
Aspirin - clinical use
acute treatment of ACS and stroke
secondary prevention of arterial thrombosis after cardiovascular and cerebrovascular events, including after arterial stents
prevention of pre-eclampsia in pregnancy
10.01 IRREVERSIBLE COX-1 INHIBITOR
Aspirin - adverse effects
GI bleeding because the cytoprotective action of PGs (namely ↓acid secretion, ↑mucus and bicarbonate) is decreased
bronchospasm in some individuals
toxic doses cause respiratory alkalosis followed by acidosis
10.01 IRREVERSIBLE COX-1 INHIBITOR
Aspirin - special points
interactions: effects increased by anticoagulants and thrombolytic drugs
10.02 ADENOSINE (P2Y12) ANTAGONISTS
Clopidogrel, prasugrel, ticagrelor - actions
prevent platelet activation
10.02 ADENOSINE (P2Y12) ANTAGONISTS
Clopidogrel, prasugrel, ticagrelor - MOA
clopidogrel and prasugrel irreversibly inhibit the binding of ADP to the purine receptor on platelets, thus inhibiting ADP-mediated platelet activation and interfering with GPIIb/IIIa-mediated platelet aggregation
ticagrelor is a reversible, non-competitive inhibitor of the P2Y12 receptor
10.02 ADENOSINE (P2Y12) ANTAGONISTS
Clopidogrel, prasugrel, ticagrelor - abs/distrib/elim
given orally, loading dose first then once daily
metabolised to an active compound
irreversible actions of clopidogrel and prasugrel mean the effects last several days until platelets are replaced
10.02 ADENOSINE (P2Y12) ANTAGONISTS
Clopidogrel, prasugrel, ticagrelor - clinical use
to prevent/treat MI and other vascular disorders
often given with aspirin
10.02 ADENOSINE (P2Y12) ANTAGONISTS
Clopidogrel, prasugrel, ticagrelor - adverse effects
bleeding, GIT discomfort, rashes, rarely neutropenia
ticagrelor can cause dyspnoea
10.03 GPIIb/IIIa RECEPTOR ANTAGONISTS
Abciximab, tirofiban, eptifibatide - actions
inhibit platelet activation
10.03 GPIIb/IIIa RECEPTOR ANTAGONISTS
Abciximab, tirofiban, eptifibatide - MOA
abciximab is a monoclonal antibody Fab fragment against the platelet GPIIb/IIIa receptor
it binds and inactivates the receptor to prevent the binding of fibrinogen, thus inhibiting platelet aggregation
tirofiban is a synthetic non-peptide and eptifibatide is a cyclic peptide based on the Arg-Gly-Asp (‘RGD’) sequence that is common to ligands for the GPIIb/IIIa receptors
10.03 GPIIb/IIIa RECEPTOR ANTAGONISTS
Abciximab, tirofiban, eptifibatide - abs/distrib/elim
given by IV injection
half-life 10-30 min
10.03 GPIIIb/IIIa RECEPTOR ANTAGONISTS
Abciximab, tirofiban, eptifibatide - clinical use
used in patients with ACS or undergoing coronary intervention to unblock artery
prevents restenosis and reinfarction
10.03 GPIIIb/IIIa RECEPTOR ANTAGONISTS
Abciximab, tirofiban, eptifibatide - adverse effects
bleeding
thrombocytopaenia
10.04 OTHER ANTIPLATELET DRUGS
Dipyridamole
causes vasodilation and inhibits platelet aggregation
prevents platelet adenosine uptake and cyclic GMP phosphodiesterase action
used in some patients with aspirin for secondary prevention of ischaemic stroke and TIAs (if clopidogrel not tolerated or contraindicated)
10.04 OTHER ANTIPLATELET DRUGS
Epoprostenol
agonist at prostanoid IP receptors
causes vasodilation and inhibits platelet aggregation
added to blood entering the haemodialysis circuit to prevent thrombosis, especially for patients in whom heparin is contraindicated
10.05 PLASMINOGEN ACTIVATORS
Alteplase, duteplase, reteplase, streptokinase - actions and MOA
enzymically activate plasminogen to give plasmin, which digests fibrin and fibrinogen, lysing the clot
10.05 PLASMINOGEN ACTIVATORS
Alteplase, duteplase, reteplase, streptokinase - abs/distrib/elim
given by IV injection or infusion
short half-life (except for reteplase)
10.05 PLASMINOGEN ACTIVATORS
Alteplase, duteplase, reteplase, streptokinase - clinical use
MI, acute ischaemic stroke and other arterial thrombosis
ideally given as soon as possible after the onset of thrombosis
occasionally used in severe cases of DVT and PE
10.05 PLASMINOGEN ACTIVATORS
Alteplase, duteplase, reteplase, streptokinase - adverse effects
bleeding (most important), reperfusion dysrhythmias, nausea and vomiting, hypersensitivity reactions
10.05 PLASMINOGEN ACTIVATORS
Alteplase, duteplase, reteplase, streptokinase - special points
streptokinase is a plasminogen-activating protein extracted from cultures of streptococci
alteplase and duteplase are single- and double-chain recombinant tissue plasminogen activators (tPA)
more active on the fibrin-bound plasminogen than on the plasma plasminogen (‘clot selective’)
action blocked by antibodies which appear about 4 days after initial dose - use of either agents should not be repeated after this time has elapsed
10.06 PLASMINOGEN INHIBITOR
Tranexamic acid - actions and MOA
inhibits plasminogen activation and thus prevents fibrinolysis
