Clinical Pharmacology of the Acute Coronary Syndrome

Question 1

What are the acute coronary syndromes?

Answer 1

Unstable angina
NSTEMI
STEMI (STEMI is a clinical emergency and can result in death at any time from presentation)

Question 2

What is needed to have an NSTEMI?

Answer 2

troponin rise
ECG changes

Question 3

What is needed to have a STEMI?

Answer 3

ST elevation
STEMI ongoing

Question 4

Stable angina?

Answer 4

ECG: normal
Troponin normal

Question 5

Unstable angina?

Answer 5

ECG: normal, inverted T waves or ST depression
Troponin normal

Question 6

NSTEMI?

Answer 6

ECG: Normal, Inverted T waves or ST depression
Troponins elevated

Question 7

STEMI?

Answer 7

ECG: Hyperacute T waves or ST elevation
Troponins elevated

Question 8

What are the goals of therapy?

Answer 8

Increase myocardial O2 supply
Coronary vasodilation
Correct hypoxaemia
Stop platelet aggregation
Stop progression to STEMI

Decrease myocardial oxygen demand
Reduce heart rate
Reduce blood pressure (afterload)
Reduce preload
Reduce contractility and wall stress

Overall, reduce the ischaemic insult

Question 9

Drugs for therapy?

Answer 9

Initial management
M - Morphine
O – Oxygen
N - Nitrates
A - Aspirin
C/T/P - Clopidogrel/Ticagrelor/Prasugrel
+ Fondaparinux (OASIS-6 trial)

Decrease myocardial oxygen demand
Bisoprolol (beta blocker)
Nitrates (not calcium channel blockers)
Ramipril (ace inhibitor)
Atorvastatin

Question 10

What are the three key antiplatelet agents?

Answer 10

Aspirin
Thromboxane-A2 inhibitor
Inhibit platelet activation and recruitment

Clopidogrel/Ticagrelor/Prasugrel
Inhibits ADP activation of P2Y12 receptor

Fondaparinux
Synthetic pentasaccharide
Binds to antithrombin III and potentiatesFactor Xa inhibition x300. Neutralization of Factor Xa decreases the conversion of prothrombin to thrombin, which subsequently decreases the conversion of fibrinogen to fibrin. Less clots.

Question 11

Goals of therapy?

Answer 11

Unblock the artery
Vasodilators don’t work
Stop platelet aggregation
Emergency angioplasty
If angioplasty not available -Thrombolysis

Question 12

How does thrombolysis work?

Answer 12

If an invasive procedure not available within 120minutes then a thrombolytic agent may be used

Recombinant tissue plasminogen activator (rtPA)
Works by converting plasminogen to plasmin (a natural fibrinolytic agent – clot buster)
Plasmin lyses clot by breaking down fibrinogen and fibrin within a clot

Question 12

What are non fibrin specific agents?

Answer 12

Catalyse systemic fibrinolysis

Streptokinase – Lower efficacy but lower bleeding risk

Recently utiliseddue to worldwide shortage of Alteplase/Tenecteplase.

Question 13

What are fibrin specific agents?

Answer 13

– all catalyse conversion of plasminogen to plasmin in absence of fibrin

Alteplase

Tenecteplase – Tenecteplase is a mutated form of alteplase with higher fibrin specificity and a longer half-life of elimination and is usually administered as a bolus infusion, whereas alteplase is usually administered as a 2-hour continuous infusion.

Question 14

Thrombolysis contraindicatoons?

Answer 14

Prior intracranial haemorrhage
Known intracranial lesion
Ischaemic stroke within 3 months
Suspected aortic dissection
Active bleeding
Significant closed head trauma (<3 months)

Question 15

Thrombolysis benefit?

Answer 15

23% reduction in mortality
39% reduction when used with Aspirin (ISIS-3 trial)

‘The Smokers Paradox’

Rescue PCI (Evidence states 2-24hrs post thrombolysis)
Invasive management is more effective – 7% reduced mortality in high risk cases
The ability to use haemodynamic support
Intra-aortic balloon pump
Impella device
Emergency surgery