AMI- Therapy

Question 1

What is included in the spectrum of ACS?

Answer 1

• Unstable angina
• NSTEMI
• STEMI
• Sudden cardiac death

Question 2

What is the common pathogenesis of ACS?

Answer 2

• Atherosclerotic plaque rupture or erosion
• Superimposed platelet aggregation and thrombosis
• Vasospasm and vasoconstriction
• Subtotal or transient total occlusion of vessel

Question 3

What is the goal of pharmacotherapy?

Answer 3

• Increase myocardial oxygen supply

- Decrease myocardial oxygen demand

Question 4

How is myocardial oxygen supply increased through pharmacotherapy?

Answer 4

Coronary vasodilation

Question 5

How is myocardial oxygen demand decreased through pharmacotherapy?

Answer 5

• Decrease in heart rate
• Decrease in blood pressure
• Decrease preload or myocardial contractility

Question 6

Patients with a STEMI have a high likelihood of what?

Answer 6

A coronary thrombus occluding the infarct artery

Question 7

What do STEMIs usually occur as result of/

Answer 7

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

Question 8

When is thrombolysis indicated?

Answer 8

If PCI is not available within 2 hours

Question 9

What are the thrombolytic agents available today?

Answer 9

Serine proteases

Question 10

How do the serine proteases work?

Answer 10

• Convert plasminogen to the natural fibrinolytic agent plasmin
• Plasmin lyses clot by breaking down the fibrinogen and fibrin contained in a clot

Question 11

What are the 2 categories of fibrinolytics?

Answer 11

• Fibrin specific agents

- Non-fibrin specific agents

Question 12

What do all fibrin specific agents do?

Answer 12

Catalyse conversion of plasminogen to plasmin in the absence of fibrin

Question 13

Give 3 examples of fibrin specific agents.

Answer 13

• Alteplase
• Reteplase
• Tenecteplase

Question 14

What are the contraindications for thrombolysis?

Answer 14

• Prior intracranial bleeding
• Known structural cerebral vascular lesion
• Known malignant intracranial neoplasm
• Ischaemic 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 15

What are the benefits of timely thrombolysis?

Answer 15

• 23% reduction in mortality

- 39% when used with aspirin

Question 16

If there is no evidence of a STEMI, what protocol should be followed?

Answer 16

ACS medical treatment protocol

Question 17

What is the ACS medical treatment protocol?

Answer 17

• Aspirin
• Tigagrelor/clopidogrel
• Fondaparinux/ LMW heparin
• IV nitrate
• Analgesia
• B-blockers

Question 18

Other than ACS medical treatment protocol, what other medications should patients be put on?

Answer 18

• Prasugrel
• Statins
• Glycoprotein IIb IIIa receptor blockers

Question 19

What is the management to reduce risk from NSTEMI?

Answer 19

• PCI or CABG
• Aspirin
• Clopidogrel, prasugrel, ticagrelor, ticlopidine or cilostazol
• LMW heparin
• Fondaparinux
• GIIb/IIIa receptor blockers
• Statins
• B blockers

Question 20

What is aspirin?

Answer 20

Antiplatelet agent

Question 21

What type of aspirin is used in ACS?

Answer 21

Low dose aspirin 75-150mg

Question 22

Why is aspirin used in ACS?

Answer 22

• The formation of platelet aggregates are important in the pathogenesis of angina, unstable angina and acute MI
• Aspirin is a potent inhibitor of platelet thromboxane A2 production
• Thromboxane stimulates platelet aggregation and vasoconstriction

Question 23

What is the benefit of regular daily us of aspirin in acute MI?

Answer 23

• Reduce mortality by 23%

- In combination with thrombolysis, reduce mortality by 42% and reinfarction by 52%

Question 24

What is the benefit of regular daily use of aspirin in unstable angina?

Answer 24

Reduce MI and death by 50%

Question 25

What is the benefit of regular daily use of aspirin as secondary prevention?

Answer 25

Reduce reinfarction by 32% and combined vascular events by 25%

Question 26

What is clopidogrel?

Answer 26

Pro drug

Question 27

What does clopidogrel do?

Answer 27

- Inhibits 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 28

What does blockade of the P2Y12 ADP receptor result in?

Answer 28

-Inhibtion of platelet aggregation by blocking activation of the GP IIb/IIIa pathway.

Question 29

What is the IIb/IIIa complex?

Answer 29

- A receptor for fibrinogen, fibronectin and von WF - Activation of this receptor is the 'final common pathway' for platelet aggregation and cross-linking of platelets by fibrin

Question 30

What are clopidogrel/ticagrelor always used in combination with?

Answer 30

Aspirin

Question 31

What is the relative reduction when clopidogrel/ticagrelor are used in combination with aspirin?

Answer 31

21%

Question 32

What is important to not with the combination use of aspirin and clopidogrel/ticagrelor?

Answer 32

- Lower incidence rate of GI bleeding however GI bleeding remain very common - Possible interaction with PPI with a reduction in effect

Question 33

Why do some people have resistance to clopidogrel?

Answer 33

- Clopidogrel is active by Cyp2C19 | - 14% of the population have low Cyp2C19 levels and demonstrate resistance to clopidogrel

Question 34

What is prasugrel?

Answer 34

Member of the thienopyridine class of ADP receptor inhibitors, like clopidogrel

Question 35

How does prasugrel compare to clopidogrel?

Answer 35

Prasugrel inihibits ADP-induced platelet aggregation more rapidly and more consistently

Question 36

Give examples of 4 different LMWH products.

Answer 36

- Enoxapirin - Dalteparin - Tinzparin - Fondaparinux

Question 37

What is fondaparinux?

Answer 37

A selective inhibitor of factor Xa

Question 38

What are the properties of fondaparinux?

Answer 38

- Single chemical entity - Synthetic pentasaccaride - Highly selective for antithrombin - Once-daily administration - No need for platelet monitoring

Question 39

What is GPIIb/IIIa?

Answer 39

- An integrin complex found on platelets | - Receptor for fibrinogen aids in platelet activation

Question 40

What does platelet activation by ADP lead to?

Answer 40

A conformational change in platelet GPIIb/IIa receptor that induced binding to fibrinogen

Question 41

Give 2 examples of drugs that target the GPIIb/IIIa receptor.

Answer 41

- Tirofban | - Abciximab

Question 42

How do IV GPIIb/IIIa inhibitors block platelet aggregation?

Answer 42

Inihibit fibrinogen binding to a conformationally activated form of the GPIIb/IIIa receptor on 2 adjacent platelets

Question 43

What is the major adverse effect of anti-thrombotic drugs?

Answer 43

Bleeding

Question 44

Why are B-blockers used post MI?

Answer 44

- In the treatment of acute MI | - For secondary prevention in the survivors of an acute MI

Question 45

Give 2 examples of B-blockers used post MI.

Answer 45

- Atenolol | - Metoprolol

Question 46

How do B-blockers work/

Answer 46

-Competitively inhibit the myocardial effects or circulating catecholamines and reduce myocardial oxygen consumption by lowering hear rate, blood pressure and myocardial contractility

Question 47

Who is at risk of cardiogenic shock?

Answer 47

- Age>70 - Heart rate>110bpm - Systolic BP<120mmHg

Question 48

Who should B-blockers not be given to?

Answer 48

- Patients at risk of cardiogenic shock | - Patients with symptoms possibly related to coronary vasospasm or cocaine use