Drugs for Antithrombotics & Anticoagulants Flashcards

Question

Hemostasis:

Answer 1

cessation of blood loss from a damaged vessel

Answer 2

formation of a blood clot

Answer 3

also called hemostatic plug, is formed by aggregation of platelets and stabilized by fibrin

Answer 4

a pathologic process in which a platelet aggregate and/or fibrin blot occludes a blood vessel

Answer 5

Normal physiological process of terminating blood loss from a vascular wall Involves: - platelet activation - coagulation cascade --> thrombin formation - clot resolution

Answer 6

1. Rupture of fibrous cap 2. Exposure of lipid core (Tissue Factor: procoagulant) 3. Platelet adherence & activation 4. Thromboxane A2 release 5. Membrane glycoprotein IIb/IIIa receptor activation to bind fibrinogen 6. Complex platelet linkage - Process above continues with further fibrin incorporation and inclusion of red blood cells within clot - End result is partial or total occlusion of vessel (coronary artery)

Answer 7

- Atherosclerosis (build up of cholesterol) may partially obstruct flow in artery - Eventually the plaque damages the endothelium - thrombus forms - Blood flow is blocked by the atherosclerosis & the thrombus - If thrombus ruptures - emboli lodge in capillary & block flow

Answer 8

blood clot attached to a blood vessel - may obstruct flow - harmful - pieces may break off which then "plug" capillaries

Answer 9

portion of thrombus that breaks away - clot floating in the blood - if "mobilized" will get stuck in capillaries - damage depends on where it lodges (heart, brain, lung)

Answer 10

on arterial & venous sides of circulation - but venous & arterial clots are different - arterial (platelet rich); venous (RBC rich)

Answer 11

- damage ENDOTHELIAL layer stimulates thrombus formation - atherosclerosis damage endothelial layer of arteries - physical damage caused by: -- balloon angioplasty -- stenting

Answer 12

- emboli lodge in cerebral capillary -- acute ischemic stroke

Answer 13

- emboli lodge in coronary artery -- acute MI

Answer 14

- involves RBC & LESS platelets -- so antiplatelet drugs are NOT as effective in veins - more related to "stagnant flow" in veins &/or atria - problem post surgery, long term bed rest or just sitting (long plane rides) - clot form & if dislodge (emboli) - flow to capillaries in the lungs -- known as pulmonary embolism - 2 major sites where venous clots form: -- lower leg veins - deep vein thrombosis (DVT) -- right atria (if atria not contracting properly)

Answer 15

1. Formation of platelet plug 2. Formation of clot 3. Breakdown of clot - if no longer needed

Answer 16

Platelet adhesion is first step in platelet plug formation: binding to exposed collagen for or von willebrand factor. Granule release In healthy vasculature, platelets are maintained in an inactive state by nitric oxide and prostacyclin (PCI2) released by endothelial cells and ADPase which degrades ADP

Answer 17

Signaling pathways involved in the regulation of platelet activation. Regulation of platelet activation occurs via the interaction of numerous effector molecules with receptors present in the plasma membranes of platelets. Several important receptors are the glycoproteins GPIb-GPIX-GPV and GPIIb-GPIIIa as described above. Numerous G-protein coupled receptors (GPCRs) are also involved in platelet functions. Five different GPCRs, their respective ligands, and brief representations of their signal transduction pathways are shown. The prostacyclin receptor is IP. The represented thrombin receptor is protease-activated receptor-1 (PAR-1). PAR-1 is knoiwn to activate both Gq- and G12/13-type heterotrimeric G-proteins. The platelet serotonin receptor is 5HT2A. The thromboxane (TXA2) receptor is TP. The platelet ADP receptor is P2Y12. Although complex, the complete signaling pathways are not shown for simplicity. Rho represents a typical member of the Rho family of monomeric G-proteins. The β and γ subunits of the Gi-type heterotrimeric G-protein associated with the ADP receptor can activate the kinase, PI3K while the α subunit simultaneously inhibits the activation of adenylate cyclase. NOS is nitric oxide synthase. Basically: -receptor binding -granule release -amplification -mediated/mediates other components of the blot clot process

Answer 18

Other NSAIDS (reversible inhibitors of COX-1) have not been shown to have anti-thrombotic efficancy and may even interfere with low-dose aspirin regimes

Answer 19

- Aspirin irreversibly blocks COX - Platelets lack a nucleus – can’t make new COX - Vascular endothelial cells have a nucleus - Vascular endothelial cells have ability to continually remake COX and hence maintain prostacyclin production

Answer 20

- Fibrinogen converted to fibrin by thrombin - Activation involves protease cleavage of fibrinogen to release fibrinopeptides that fit into pre-formed holes in other fibrin monomers to form a fibrin gel - Fibrin monomers are initially bound non-covalently - Activation of factor XIII by thrombin results in activation of this enzyme that catalyzes interchain covalent cross links

Answer 21

International Normalized Ratio (INR) - Ratio of the patient's (with Warfarin) pro-thrombin time to that of a control subject (with no Warfarin) - Pro-thrombin time is a measurement (in sec's) of the EXTRINSIC pathway - Target INR is 2.0-3.0 - INR <2 may lead to thrombotic complications - INR >3 may lead to bleeding

Answer 22

- these drugs do NOT distinguish b/t fibrin of a beneficial hemostatic plug & unwanted thrombi - will decrease thrombi, but may cause bleeding in an unknown lesion (ex: peptic ulcer)

Answer 23

breaks down clot Plasminogen activators: - tPA - uPA are syn. in endothelial cells, released in conditions of blood stasis

Answer 24

- tPA plays predominant role in intravascular fibrinolysis - tPA is released from endothelial cells in response to stimuli such as stasis - tPA activity increases 300-fold in presence of fibrin - tPA is rapidly cleared or inhibited by plasminogen activator inhibitor (PAI-1 and/or PAI-2) - Plasmin is inhibited by alpha-2-antiplasmin (occurs when plasmin not bound to fibrin)