Clinical Pharmacology of Acute Coronary Syndrome

Question 1

What is included in ACS ?

Answer 1

Unstable angina
STEMI
NSTEMI

Question 2

What is the pathogenesis of ACS ?

Answer 2

Atheroscleorsis plaque rupture
Superimposed plaque aggregation and thrombosis
Vasospasm and vasoconstriction
Subtotal or transient total occlusion of vessel

Question 3

What is the goal of pharmacology ?

Answer 3

Increase myocardial O2 demand:
	- Thrombolysis 
	- Coronary vasodilation
Decrease myocardial oxygen demand
	- Decrease in HR
	- Decrease BP
        - Decreased preload or myocardial contractility

Question 4

What is the risk with pateints with STEMI ?

Answer 4

High likelihood of coronary thrombosis occluding the infacrt artery

Question 5

When is thrombolysis most effective ?

Answer 5

Within 2 hours of symptoms

Question 6

When can thrombolysis be given within 12hrs of onset of symptoms ?

Answer 6

If primary PCI cannot be delivered within 2hrs of the time when fibrinolysis could have been given

Question 7

What are the 2 categories of fibrinolytic ?

Answer 7

Fibrin-specific agents:
- Altepase
- Reteplase
- Tenecteplase
- All catalyse conversion of plasminogen to plasmin in the absence of fibrin
Non-fibrin-specific agents such as streptokinase catalyse systemic fibrinolysis

Question 8

What are the contraindications of thrombolysis ?

Answer 8

Prior intracranial haemorrhage (ICH)
Known structural cerebral vascular lesion
Known malignant intracranial neoplasm
Iscahemic stroke within 3 months
Suspected aortic dissection
Active bleeding or bleeding diathesis ( excluding menses)
Significant closed-head trauma or facial trauma within 3 months

Question 9

What are the benefits of thrombolysis ?

Answer 9

Prior intracranial haemorrhage (ICH)
Known structural cerebral vascular lesion
Known malignant intracranial neoplasm
Iscahemic stroke within 3 months
Suspected aortic dissection
Active bleeding or bleeding diathesis ( excluding menses)
Significant closed-head trauma or facial trauma within 3 months

Question 10

What is dual anti-platelet therapy ?

Answer 10

Aspirin 300mg immediately and then continuous at 75-150mg daily
If scheduled for PCI:
- Then prasugrel plus aspirin

Question 11

What is the treatment protocol if there is no evidence of STEMI ?

Answer 11

Aspirin
Ticagrelor/clopidogrel
Fondaparinux
IV nitrate 
Beta blockers 
Statins
Analgesia

Question 12

What dose of aspirin should be given ?

Answer 12

Low dose of 75-150mg

Question 13

What does aspirin inhibit ?

Answer 13

Platelet thromboxane A2 production

Question 14

What does thromboxane stimulate ?

Answer 14

Platelet aggregation and vasoconstriction

Question 15

What does aspirin do in acute MI ?

Answer 15

Reduce cardiovascular death, non-fatal MI and non-fatal stroke by nearly a third (absolute RR 3.8%, relative RR 30%)
in combination with thrombolysis reduce mortality by 42% and reinfarction by 52%

Question 16

What does aspirin do in unstable angina ?

Answer 16

Halves the rate of vascular events (cardiovascular death, non-fatal MI and non-fatal stroke) (absolute risk reduction 5.3%, relative RR 46%)

Question 17

How can aspirin be used in secondary prevention ?

Answer 17

Reduce reinfarction by 32%

Combined vascular events by 25%

Question 18

What do ticagrelor and clopidogrel inhibit ?

Answer 18

ADP receptor activated platelet aggregation
Specifically and irreversibly inhibits the P2Y12 ADP receptor which is important in aggregation of platelets and cross-linking by fibrin

Question 19

What is prasugrel ?

Answer 19

Member of the thienopyridine class of ADP receptors inhibitors, like ticagrelor 
Compared to clopidogrel prasugrel inhibits ADP–induced platelet aggregation more rapidly, more consistently

Question 20

What is Fondaparinux ?

Answer 20

A Selective Inhibitor of Factor Xa
Single chemical entity
Synthetic pentasaccaride
Highly selective for antithrombin 
Once-daily administration
No need for platelet monitoring

Question 21

What are B-blockers used for ?

Answer 21

In the treatment of acute MI

For secondary prevention in the survivors following an acute MI