Acute Coronary Syndrome and Acute Myocardial Infarction Therapy

Question 1

What is the basic spectrum of acute coronary syndromes?

Answer 1

Unstable angina
Non-ST elevation MI
ST elevation MI
Sudden cardiac death

Question 2

What is the goal of pharmacotherapy in acute coronary syndrome?

Answer 2

Increase myocardial oxygen supply through coronary vasodilation
Decrease myocardial oxygen demand through decreasing HR, BP and preload/contractility

Question 3

What is there a risk of in patients with STEMI?

Answer 3

High likelihood fo coronary thrombus occluding the infarcted artery

Question 4

Angiographic evidence of a coronary thrombus formation is seen in what percentage of patients with STEMI?

Answer 4

More than 90%

Question 5

What is a STEMI usually the result of?

Answer 5

Coronary artery occlusion due to the formation of thrombus overlying an atheromatous plaque

Question 6

When is thrombolysis indicated?

Answer 6

If there can be no access to the cath lab within 2 ours

Question 7

What are the thrombolytic agents available today? How do they work?

Answer 7

Serine proteases that work by converting plasminogen to plasmin
Plasmin lyses the clot by breaking down the fibrin and fibrinogen contained within it

Question 8

Fibrinolytics are divided into two categories, what are these? Give an example of each

Answer 8

Fibrin specific agents e.g. alteplase, reteplase, tenecteplase
Produce limited plasminogen conversion in the absence of fibrin

Non-fibrin specific agents e.g. streptokinase
Catalyse systemic fibrinolysis

Question 9

Why can antibody-generating agents not be used more than once?

Answer 9

They will cause an anaphylactic response on subsequent exposure

Question 10

What are the contraindications to thrombolysis?

Answer 10

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

Question 11

What are the benefits of thrombolysis?

Answer 11

Timely thrombolysis associated with 23% reduction in mortality, or 39% reduction when used with aspirin
Immediate reduction in death rate shown to continue throughout life, morbidity and mortality are significantly reduced over time

Question 12

What is the dose of aspirin used in treatment of MI?

Answer 12

300mg loading dose then 75-150mg daily

Question 13

How can aspirin be used to treat MI?

Answer 13

Formation of platelet aggregates is important in the pathogenesis of MI
Thromboxane stimulates platelet aggregation and vasoconstriction
Aspirin is a potent inhibitor of platelet thromboxane production

Question 14

What effect can the regular daily use of aspirin have on mortality in acute MI?

Answer 14

Can reduce mortality by 23%

In combination with thrombolysis it can reduce mortality by 42% and reinfarction by 52%

Question 15

What effect can the regular daily use of aspirin have in unstable angina?

Answer 15

Reduce MI and death by 50%

Question 16

What effect can the regular daily use of aspirin have in secondary prevention?

Answer 16

Reduce re-infarction by 32% and combined vascular events by 25%

Question 17

What is the standard dose of clopidogrel used in treatment of MI?

Answer 17

300mg loading dose then 75mg once daily

Question 18

How does clopidogrel work?

Answer 18

Inhibits ADP receptor-activated platelet aggregation
Specifically and irreversibly inhibits the P2Y12 ADP receptor which inhibits platelet aggregation by blocking activation of the GP IIb/IIIa pathway

Question 19

What is the IIb/IIIa complex a receptor for?

Answer 19

Fibrinogen, fibronectin and vWF

Question 20

What is the activation of IIb/IIIa complex the final common pathway for?

Answer 20

Platelet aggregation and the cross-linking of platelets by fibrin

Question 21

What drug is clopidogrel used in combination with?

Answer 21

Aspirin

Question 22

What is the relative risk reduction when clopidogrel is used in combination with aspirin?

Answer 22

21%

Question 23

What percentage of the population will demonstrate resistance to clopidogrel?

Answer 23

14% due to low CYP 2C19 levels

Question 24

What class of drug is prasugrel?

Answer 24

Member of the thienopyridine class of ADP receptor inhibitors

Question 25

What is the difference between prasugrel and clopidogrel?

Answer 25

Prasugrel inhibits ADP-induced platelet aggregation more rapidly and more consistently, and doesn't rely on metabolism in the liver

Question 26

What are the products of low molecular weight heparin?

Answer 26

Enoxaparin Dalteparin Tinzeparin Fondaparinux

Question 27

Why is fondaparinux recommended?

Answer 27

Single chemical entity Highly selective for its target Once daily administration No need for platelet monitoring

Question 28

What is glycoprotein IIb/IIIa?

Answer 28

Integrin complex found on platelets | Receptor for fibrinogen aids in platelet activation

Question 29

What does platelet aggregation by ADP lead to in platelet glycoprotein IIb/IIIa receptors?

Answer 29

Conformational change that induces binding to fibrinogen

Question 30

What do drugs such as abciximab and tirofiqan reduce at 30 days of treatment?

Answer 30

Composite end point of death, re-infarction and need for urgent revascularisation by 46% at 30 days, and by 20% at 6 months

Question 31

Give an example of a glycoprotein IIb/IIIa receptor inhibitor

Answer 31

Abciximab | Tirofiban

Question 32

What is the major adverse effect of glycoprotein IIb/IIIa receptor inhibitors?

Answer 32

Bleeding Major bleeding in 1.4% of patients Minor bleeding in 10.5% Blood transfusion required to terminate bleeding and improve bleeding-related anaemia in 4% of all patients

Question 33

What is the reduction in mortality following an MI produced by IV atenolol or metoprolol?

Answer 33

10-15%

Question 34

Oral beta blockade started weeks or months post-MI can reduce cardiac death and second MI by what?

Answer 34

Reduce cardiac death by 22% | Reduce second MI by 26%

Question 35

What are the common complications following an MI?

Answer 35

``` Arrhythmia Cardiogenic shock Myocardial rupture Valve dysfunction Papillary muscle dysfunction/rupture Acute ventricular septal defect ```

Question 36

What are the long-term complications of MI?

Answer 36

Higher risk of bleeding due to anti-platelet medication Increased risk of further MI/death Cardiac failure

Question 37

What is necessary before discharging a patient from hospital following an MI?

Answer 37

Check that they are on the correct medications Address risk factors Cardiac rehabilitation Follow up plans

Question 38

Why are anti-platelets needed in patients who have a coronary stent?

Answer 38

Takes some time for the stent to become endothelialised (embedded into coronary artery wall) During this time the metal stent is exposed to the blood and can cause thrombosis and block off the stent, unless patient is on anti platelet therapy

Question 39

What is the typical medical treatment protocol of acute coronary syndrome if there is no evidence of STEMI?

Answer 39

Aspirin 300mg loading dose then 75mg once daily Clopidogrel 300mg loading dose then 75mg once daily Fondaparinux 2.5mg once daily subcutaneous or LMWH Intravenous nitrate Analgesia Beta blockers 2.5mg once daily ACEI 1.25mg twice daily ``` Other medications; Prasugrel Ticagrelor Glycoprotein IIb/IIIa receptor blockers Statins ```

Question 40

What can be used in management of ACS to reduce the risk from NSTEMI?

Answer 40

``` PCI or CABG Aspirin Clopidogrel, prasugrel, ticagrelor, ticlopidine or cilostazol LMWH Fondaparinux Glycoprotein IIb/IIIa receptor blockers Beta blockers ```