ANTI-PLATELETS AND ANTI-COAGULANTS Flashcards
THE cardiocascular system is a _______ ______ system, which regulates its own _____ and ________.
closed, hydraulic, pressure, function.
the first step of vessel damage is _______ to ______ the blood flow in the injured area
vasospasm, reduce
during the coagulation process the ______ aggregates is stabilized by a _________ which is then removed once the vessel is repeaired by process called _______
platelet, fibrin clot, fibrinolysis
Hemostasis VS Thrombosis
- hemostasis, the balance between pro-coagulant and anti-coagulant in the blood vessel, once the blood vessel is damaged there is the formation of a platelet-fibrin clot which is removed by fibrinolysis once the blood vessel is repaired.
- thrombosis, abnormal stimulation of platelet aggregation and blood coagulation following an injury, excessive clotting especially in areas of atherosclerosis, leads to MI/stroke, DTV, venous occlusion
anticoagulant drugs _______ _______ and prevent occurence of a _______
antiplatelet drugs _______ platelet ________.
Fibrilonytic drugs are used in _____________, to destroy the _______.
retard coagulation, thrombus, prevent, aggregation.
emergency, thrombus
platelet at rest are _____ shaped, if vessel injury and exposion of the _______ ______, collagen binds to _______ on the surface of the platelets activating them by release of _______ which increases ________ and promotes patelet aggregation.
disc, subendothelial matrix, GPIa receptor, mediators, expression of receptors on platelet surface.
Adhesion of platelets is also mediated by interaction of ________ and GP_____ receptor on platelet surface.
activated platelets have ______ shape with ______
generation of mediators like _____ which increase _______ expression and aggregation of platelets is stabilized by _______ matrix that _______ platelets togheter forming fibrin clot.
von Willebrand factor (vWF), 1b
spheric, pseudopodia
thromboxane, receptors, fibrinogen, crosslink
once platelet are activated ________ is produced which is then converted into COX-1 and from that _______ is synthetised.
arachidonic acid, thromboxane.
NAC OF ASPIRIN (ASA- ACETYLSALICYLIC ACID)
- NATURE. irreversible COX-1 inhibitor,
- ACTION, cox-1 generates TXA2 which is a platelet agonist so creates a positive feedback loop, once aspirin blocks cox-1 in the platelets they can’t replace it because they have no nucleus so TXA2 remains suppressed till a new cohort of platelets is produced (turnover of 10 days)
- C. at low doses 75mg has antiplatelet action, given daily in pt with risk of arterial thrombosis, at high doses 300mg/4h, inhibits also COX-2 which is usually produced in case of fever/pain/severe inflammation so has an antipyretic and anti-inflammatory effect.
S/E OF ASPIRIN
- GI upset and bleeding because inhibits also PGE2 made by COX-1 which is protective towards gastric mucosa
- rare Risk of Stroke
- risk dose-dependent given to patients at greater risk of thrombosis, not in population without risk factors
- lower s/e with lower dose 75mg
other antiplatelet drugs are ______.
ADP is secreted during platelet activation and binds to _____ receptors to _____ platelet response
ADP antagonist, G-protein, amplify
Clopidogrel is ADP antagonist at ______ receptor, it’s a ________ and has the same effect of ________.
Prasugrel is a ________ thienopyridine compound, has a faster _____ is effect is more ______ into inhibiting platelet aggregation
P2Y12, aspirin, third generation, onset of action, robust and uniform
Nature and pharmacokinetics OF TIGRELOR
- NATURE, reversible non-competitive P2Y12 receptor inhibitor
- pharmacokinetics, the level of inhibition is related to plasma levels of ticagrelor, given orally, half-life 12h, no prodrug, faster onset of action than clopidogrel
there are two pathways of the coagulation cascade the _____ and ______
they have a final _____ pathway, in which ______ is converted into thrombin, _______ into fibrin which then is crosslinked to create fibrin clot.
intrinsic, extrinsic, common, prothrombin, fibrinogen
there are two pathways of the coagulation cascade the _____ and ______
they have a final _____ pathway, in which ______ is converted into thrombin, _______ into fibrin which then is crosslinked to create fibrin clot.
intrinsic, extrinsic, common, prothrombin, fibrinogen
the intrinsic pathway is activated by ________
the extrinsic pathway is activated by ________
- formation of red thrombus due to abnormal vessel wall
- tissue injury
CLASSIFICATION OF ANTICOAGULANTS
- ORAL ANTICOAGULANT, indirect (warfarin) and direct action (DOACs like direct thrombin inhibitor and factor Xan inhibitor)
- parenteral anticoagulant, indirect( activity mediated by plasma cofactors, like Heparin or LMWH) and direct actions
NAC OF WARFARIN
- NATURE. vitamin K antagonist
- ACTION, inhibit activation of vitamin K and synthesis of clotting factors
- CONSEQUENCES, prevent thrombosis in high-risk patients (immobilized, h/o DVT, unstable angina/ prosthetic heart valves)
S/E AND LIMITATIONS OF WARFARIN
- LIMITATIONS, delayed onset of action because of time required to deplete the pool of clotting factors 3-5 days, lots of drug-drug interactions, risk of hemorrhage (liver disease, hyperthyroidism drugs that inhibit hepatic metabolism, inhibits platelet function, reduction of vit K), reduced warfarin effect ( with hypothyroidism, vit k, drugs that induce CP450)
- S/E, bleeding, fetal hemorrhage(contraindicated in pregnancy), drug interactions
DOACs
- inhibit directly activated coagulation proteases (thrombin/factor Xa)
- same effect as warfarin
- predictable dose, no food interactions, limited drug interactions, rapid onset and off-set action
Heparins are naturally occurring family of __________ found in mast cells and ______________. they bind and _______ the action of ________, which is an endogenous inhibitor of the coagulation cascade.
Heparin changes _____ of antithrombin III and accelerate its ________
polysaccharides, endothelium, accelerate, antithrombin 3, conformations, rate of action
HEPARIN is given ______, among side effects there are: risk of ______, osteopenia, hyperkalemia and ____________
parenterally, bleeding, heparin-induced thrombocytopenia
