Antiplatelet agents

Question 1

what are platelets

Answer 1

1. cell fragments, 3um in diameter, formed from megakaryocytes
   - have no nucleus
2. process driven by hormone known as thrombopoietin

Question 2

what is platelet activation/aggregation

Answer 2

1. platelets activated by contact with collagen
2. release preformed vasoconstrictors
3. expression of active GPIIb/IIIa receptors on surface of platelet
4. fibrinogen cross links platelets via GPIIb/IIIa receptors
5. fibrinogen allows plug formation

Question 3

what is purport

Answer 3

pinpoint haemorrhages

Question 4

what are anti platelet agents

Answer 4

block platelet activation and aggregation and are good for treating arterial disease

Question 5

give an example of an anti platelet agent

Answer 5

aspirin

Question 6

give examples of ADP antagonists

Answer 6

clopidogrel, prasugrel, and ticagrelor

Question 7

what is cangrelor

Answer 7

1. P2Y12 antagonist
2. reversible
3. for iV injection
4. fast onset and fast offset due to short half life
   - normal platelet function restored after 1 hour

Question 8

give examples of GPIIb/IIIa antagonists

Answer 8

abciximab (non competitive mAB)

eptifibatide and tirofiban (receptor antagonists)

Question 9

what are class 1 GPIIb/IIIa antagonists

Answer 9

abciximab

• tightly bound agents
• long acting
• low plasma concentration
• IIb/IIIa inhibitor circulates bound to platelet receptor

Question 10

what are class II GPIIb/IIIa antagonists

Answer 10

tirofiban and eptifibatide

• short acting agents
• high plasma concentration
• highly reversible binding

Question 11

what does IV dosing give and what does oral dosing lead to

Answer 11

• IV dosing gives constant inhibition of ADP receptor

- oral leads to peaks and troughs and risk of not being protected

Question 12

give examples of anti platelets that increase cAMP

Answer 12

• dipyridamole, and epoprostenol

Question 13

why can’t platelets synthesise new proteins

Answer 13

they don’t have a nucleus

Question 14

explain why aspirin reduces platelet activation and aggregation

Answer 14

1. aspirin binds irreversibly to cOX 1
2. endothelial cells have a nucleus so can bypass the aspirin block by synthesising new COX1 and then synthesising PGI2 which causes vasodilation and increases cAMP to stop the activation and aggregation of platelets
3. platelets do not have a nucleus, so new platelets need to be formed to bypass the block of COX 1
4. aspirin also has a high first pass metabolism so platelets in the hepatic portal vein will see a high conc of aspirin, but most of the endothelial cells will not

Question 15

what physiological signalling pathways are responsible for enabling the heart to increase its workload to meet the needs of the body
Describe how cardiac workload is regulated

Answer 15

1. end diastolic volume (preload) regulated by sympathetic system, RAAS
   - contractility of venues , Na+ and h2o retention
2. heart rate
3. contractility
4. total peripheral resistance

Question 16

how can problems with heart valves lead to angina

Answer 16

1. stenosis- more difficult to open valves
   - so heart has to work more forcibly to open valve and this increases workload
   - this increased work if not matched by an increase in oxygen and nutrient supply will lead to angina
2. regurgitation- valves are leaky, so when the heart contracts, not all the blood in the ventricles will make it into systemic circulation
   - therefore, the heart has to work harder to maintain an appropriate cardiac output
   - this increased work if not matched by an increase in oxygen and nutrient supply will lead to angina

Question 17

how would you diagnose someone with stable angina

Answer 17

1. predictable pain brought on by exercise and relieved by rest
2. ST depression on an eCG
3. angiography to show physical state of coronary arteries