Week 10- Antiplatelets

Question 1

what is haemostasis?

Answer 1

arrest of blood loss from damaged blood vessels

Question 2

what is is throbosis?

Answer 2

pathological formation of clot in vasculature in the

absence of bleeding (no loss of blood)

Question 3

what is haemostais promotion?

Answer 3

when you promote blood clotting, defects

Question 4

what is a platetlet?

Answer 4

cells that circulate in the blood and bind together when they recognise damaged blood vessels

Question 5

what is the role of platelets?

Answer 5

-for integrity of circulation
-essential for haemostasis, healing of vessels and
inflammation

Question 6

what are some properties of platelets?

Answer 6

 Adhesion following vascular damage
 Shape change
 Secretion of granule contents
 Biosynthesis of PAF and prostaglandins
 Aggregation
 Exposure of acidic phospholipid on surface

Question 7

what is the mechanism for platelet activation?

Answer 7

• they float in blood and activate when they recognise damage
• when their is endotheilal cell damage this leads to exposure of the basement layer (extracelluslar matrix)
• two components that can activate platelets of the extracellular matrix is the von williebrand factor and collagen
• tehir antigens for these components on the platetlets CS

Question 8

how does aggregation of platelets occur?

Answer 8

• platelet aggregation will lead to platelet activation
• exposure of collagen and von willebrand factor will bind to the receptors on the platelet and lead to activation
• platelet activation will lead to further platelet aggregation
• their are receptors that will bind to fibrin and fibrin will form links between the platelets causing aggregation and further activation
• platelet plug will form leading to blockage
• platelet contraction occurs due to changes

Question 9

what affects platelet aggregation negatively?

Answer 9

• nitric oxide
• prostacylin
• they are released into the blood and inhibit activation and aggregation

Question 10

how can we influence platelet aggregation NEGATIVELY ? through inhibitor

Answer 10

• by targeting ADP and thromboxane A2 as these normally help
• by inhibiting them binding/being release
• can block von williebran factor and collagen from bidning to recptors on platelet factor will prevent activation

Question 11

how can we influence platelet aggregation NEGATIVELY ? through stimulation

Answer 11

stimulate nitric acid and prostacyclic which are the inhibitors of aggregation/activation
-less ADP less activation

Question 12

what are some of the platelets activators?

Answer 12

• TxA2
• ADP
• Collagen
• fibrinogen

Question 13

what are some antiplatelet drugs and what do they do?

Answer 13

Decrease platelet aggregation and inhibit
thrombus formation in arterial circulation
-aspirin
- Thienopyridines – Clopidogrel (prasugrel, ticlopidine)
 Ticagrelor
 Glycoprotein IIb/IIIa inhibitors
 Eptifibatide
 Tirofiban
 Abciximab
 Dipyridamole

Question 14

what is the pharmacology of aspirin, how does it work in the body?

Answer 14

• IRREVERSIBLY inactivates cyclooxygenase (COX)
• important as COX1 is found in the platelets themselves and improtant for platelet aggregation and homestasis
• COX2 is important for platelet aggregation

Question 15

why are COX1+2 important?

Answer 15

cox 1 is responsible for the synthesis of Thromboxane A2 in the platelets when they are activated COX1 ACTIVITY IS ESSENTIAL for THE PRODUCTION OF IT and cox2 in endothelial cells formation PGI2 (prostacyclin) which is the inhibitor of platelets activation

Question 16

why is the role of aspirin weird?

Answer 16

it inhibits a promoter which is throboxane which normally promotes platelets aggregation and inhibits prostacyclin which is an inhibitor of aggregation

Question 17

how does aspirin effect COX1?

Answer 17

- IRREVERSIBLY inactivates COX 1 in platelets
 Reduces thromboxane A2 formation
 Reduces platelet aggregation

Question 18

how does aspirin effect COX2?

Answer 18

 IRREVERSIBLY inactivates COX 2
in endothelium
 Reduces prostacyclin formation
 Increases platelet aggregation

Question 19

why does aspirin work if it results in a net zero effects?

Answer 19

-Endothelial cells can synthesise new COX 2
Platelets cannot because no nuclei!
-over time endotheil cells will make more COX2 and make more prostacyclin which inhibits.
-Lower doses just inhibit platelets
Higher doses inhibit both

Question 20

what are Clopidrogel & Prasugrel?

Answer 20

-Thienopyridines - Pro-drugs Additive effects to aspirin, because
work on separate pathway
-Inhibit ADP-induced aggregation (ADP receptor antagonists)
 Antagonise the platelet P2Y12 receptor (purinergic receptor)

Question 21

what is ticagrelor?

Answer 21

 Nucleoside analogue – like adenosine
 Blocks P2Y12 ADP receptors on platelets
 Different binding site than ADP so allosteric inhibitor and blockage reversible and therefore acts faster and for shorter period
 PLATO trial – ticagrelor less mortality from all CV causes
than clopidogrel
 Side effects – more non-lethal bleeding – effects more
quickly reversible though

Question 22

what is Glycoprotein IIB/IIIA receptor

antagonists

Answer 22

 Inhibit all pathways of platelet activation because bind to glycoprotein
IIb/IIIa receptors, blocking fibrinogen binding so inhibiting
aggregation