ANTI-PLATELETS AND ANTI-COAGULANTS

Question 1

THE cardiocascular system is a _______ ______ system, which regulates its own _____ and ________.

Answer 1

closed, hydraulic, pressure, function.

Question 2

the first step of vessel damage is _______ to ______ the blood flow in the injured area

Answer 2

vasospasm, reduce

Question 3

during the coagulation process the ______ aggregates is stabilized by a _________ which is then removed once the vessel is repeaired by process called _______

Answer 3

platelet, fibrin clot, fibrinolysis

Question 4

Hemostasis VS Thrombosis

Answer 4

• 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

Question 5

anticoagulant drugs _______ _______ and prevent occurence of a _______

antiplatelet drugs _______ platelet ________.

Fibrilonytic drugs are used in _____________, to destroy the _______.

Answer 5

retard coagulation, thrombus, prevent, aggregation.

emergency, thrombus

Question 6

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.

Answer 6

disc, subendothelial matrix, GPIa receptor, mediators, expression of receptors on platelet surface.

Question 7

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.

Answer 7

von Willebrand factor (vWF), 1b

spheric, pseudopodia

thromboxane, receptors, fibrinogen, crosslink

Question 8

once platelet are activated ________ is produced which is then converted into COX-1 and from that _______ is synthetised.

Answer 8

arachidonic acid, thromboxane.

Question 9

NAC OF ASPIRIN (ASA- ACETYLSALICYLIC ACID)

Answer 9

• 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.

Question 10

S/E OF ASPIRIN

Answer 10

• 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

Question 11

other antiplatelet drugs are ______.

ADP is secreted during platelet activation and binds to _____ receptors to _____ platelet response

Answer 11

ADP antagonist, G-protein, amplify

Question 12

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

Answer 12

P2Y12, aspirin, third generation, onset of action, robust and uniform

Question 13

Nature and pharmacokinetics OF TIGRELOR

Answer 13

• 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

Question 14

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.

Answer 14

intrinsic, extrinsic, common, prothrombin, fibrinogen

Question 14

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.

Answer 14

intrinsic, extrinsic, common, prothrombin, fibrinogen

Question 15

the intrinsic pathway is activated by ________

the extrinsic pathway is activated by ________

Answer 15

• formation of red thrombus due to abnormal vessel wall
• tissue injury

Question 16

CLASSIFICATION OF ANTICOAGULANTS

Answer 16

• 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

Question 17

NAC OF WARFARIN

Answer 17

• 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)

Question 18

S/E AND LIMITATIONS OF WARFARIN

Answer 18

• 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

Question 19

DOACs

Answer 19

• 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

Question 20

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 ________

Answer 20

polysaccharides, endothelium, accelerate, antithrombin 3, conformations, rate of action

Question 21

HEPARIN is given ______, among side effects there are: risk of ______, osteopenia, hyperkalemia and ____________

Answer 21

parenterally, bleeding, heparin-induced thrombocytopenia