Acute Coronary Syndrome

Question 1

What is ACS?

Answer 1

acute coronary syndrome

Question 2

Give the definition of ACS

Answer 2

It describes a group of clinical conditions, all of which usually present with chest pain or discomfort resulting from myocardial ischeamia. The distinct categories of ACS are distinguished initially by the presence or absence of ST-segment elevation on a 12-lead ECG (electrocardiogram) and in those without ST-elevation, by the presence or absence of a raised blood troponin concentration suggesting myocardial injury.

Question 3

Give examples of different ACS

Answer 3

unstable angina, acute MI, STEMI, NSTEMI

Question 4

What is MI?

Answer 4

myocardial infarction

Question 5

What is STEMI?

Answer 5

ST-segment elevation myocardial infarction

Question 6

What is NSTEMI?

Answer 6

Non-ST segment elevation myocardial infarction

Question 7

What is ischaemia?

Answer 7

when a coronary artery is blocked or narrowed, blood flow to the heart muscle is reduced, leading to ischaemia (lack of oxygen).

Question 8

Give the definition for unstable angina

Answer 8

a form of chest pan caused by insufficient blood flow and oxygen supply to the coronary arteries. This can be caused by a thrombus forming on a ruptured atherosclerotic plaque.

Question 9

What is the pathophysiology of STEMI?

Answer 9

a complete occlusion of blood flow through the coronary artery to the myocardium. The rupture/erosion of an unstable plaque within the coronary artery exposes the thrombogenic material (lipids/fats) underneath the plaque. The circulating platelets then accumulate (platelet aggregation) at the site of injury and forms a thrombus. The thrombus fully occludes the coronary artery resulting in a reduction in oxygenated blood flow, causing an infarction to the myocardium.

Question 10

What is the pathophysiology of NSTEMI?

Answer 10

It is commonly caused by a disruption of a coronary artery atherosclerotic plaque, with myocardial ischaemia and injury often resulting from partial or intermittent occlusion. Stable plaque in arteries can lead stenosis or narrowing of the arteries. This involves an imbalance between the myocardial oxygen demand and supply which is due to a reduction in myocardial perfusion. Only detected by a rise of cardiac biomarkers (troponin) in the blood without the ST-elevation being noticed in the ECG.

Question 11

What is the difference between NSTEMI and STEMI?

Answer 11

A STEMI is a complete occlusion of a coronary artery due to the rupture of a plaque and an intracoronary thrombus has occurred. Whereas NSTEMI, is a partial occlusion of a coronary artery reducing blood flow to the myocardium.

Question 12

What is the definition for myocardial infarction?

Answer 12

occurs when blood flow decreases or stops in one of the coronary arteries of the heart

Question 13

What is MI also known as?

Answer 13

heart attack

Question 14

Give the definition of atherosclerosis

Answer 14

a condition that forms atheroma (a fatty plaque) which causes a gradual occlusion of the coronary arteries.

Question 15

What is pathophysiology of pain in ACS?

Answer 15

Without oxygen, glucose is still broken down into pyruvate, however there will be a reduced ATP. The cellular energy process becomes less efficient and produces lactic acid which releases H+ (hydrogen ions/protons) and lactate. H+ and lactate stimulates nociceptors which creates the pain response responsible in angina or MI.

Question 16

What is the pathophysiology of atheroma formation?

Answer 16

endothelial cell damage caused by smoking/diabetes and other high-risk factors. Circulating (low density lipoproteins) and WBC (white blood cells) infiltrate the tunica intima. WBC produces ‘free radical’ and oxidise LDL causing them to be engulfed by WBC. ‘Foam cells’ die and its contents become engulfed by other WBC and smooth muscles. Lipids and fragments of dead cells produce a lipid core which is covered by endothelial cells. Accumulation of calcium salts and more dead cells occur causing it to harden.

Question 17

What is the pathophysiology of thrombus formation?

Answer 17

Exposure of the thrombogenic material/damaged tissue triggers platelet adhesion and activation. COX-1 activates the thromboxane A2 pathway which causes the expression of fibrin receptors (GPIIb/IIIa) on the outside of the platelets. Fibrin strand attachment causes further platelets to attach and aggregation to occur. Activated platelets also releases ADP signallers to inactive platelets, activating fibrin receptors, causing more platelets aggregation and thrombus formation.

Question 18

Explain the pathophysiology of thromboxane A2 pathway

Answer 18

The cyclo-oxygenase 1 (COX-1) is a platelet enzyme that activates the thromboxane A2 pathway. Thromboxane A2 increases the expression of fibrin receptors (GPIIb/IIIa) that help platelets bind to fibrin. Thromboxane A2 has prothrombotic properties that stimulates platelet change, aggregation and secretion which promotes thrombus formation and thrombosis.

Question 19

What is the 1st line drug treatment used for STEMI and NSTEMI? include route and dosage

Answer 19

Aspirin 300mg with route of chewed or dispersed in water.

Question 20

What does GTN mean?

Answer 20

Glyceryl trinitrate

Question 21

What is the pharmacodynamics of GTN?

Answer 21

nitroglycerin causes venodilation (dilation of the veins) which reduces central venous pressure which in turn reduces the amount of blood returning to the heart. This reduces pre-load which in turn reduces the force of contraction. Vasodilation of coronary arteries is where blood flow to the heart muscle is increased together with more oxygen. This reduces lactic acid production this reduces pain. Vasodilation of larger arteries reduces the amount of work needed to pump blood in the body.

Question 22

What is the pharmacodynamics of aspirin?

Answer 22

Aspirin irreversible inhibits COX-1 in platelets from activating the thromboxane A2 (TXA2) pathway. By reducing TXA2 production, aspirin decreases platelet activation and aggregation. The inhibition of TXA2 prevents the expression of fibrin receptors (GBIIb/IIIa) on the surface of the platelet, preventing further platelets to attach/aggregation. Therefore, prevents the formation of thrombus.

Question 23

What is the medical term for beta-blockers?

Answer 23

beta-adrenergic receptor blockers

Question 24

Give examples of beta blockers

Answer 24

bisoprolol, atenolol, propranolol

Question 25

What is the pharmacodynamics of beta-blockers?

Answer 25

They bind to and block beta-1 receptors on the heart (AV and SA node and the myocardium) which reduces its responsiveness to sympathetic activity. The heart then decreases its activity in response. By blocking the receptors, it keeps the heart rate and contractility low and so reduces the workload of the heart so that the oxygen demand can be met. In kidneys, beta blockers cause a reduction of renin release and reduces circulation of angiotensin II. Beta blockers reduces hypertension by lowering cardiac output by blocking beta-1 receptors.

Question 26

What is the pharmacodynamics of statins?

Answer 26

It causes breakdown of the mevalonate in the liver/hepatocytes by blocking HMG-CoA Reductase. It causes a reduction in the production of LDL cholesterol, therefore, triggers an increase in LDL receptors in the liver cell to pull more LDL from the blood stream to the liver. This also slows down the atheroma formation on the vascular wall which reduces the chance of rupture and thrombus formation, thus reducing the risk for ACS.

Question 27

What is the pharmacokinetics of GTN in terms of absorption and metabolism?

Answer 27

A - it is absorbed as a sublingual spray or taken as a tablet under the tongue where it is quickly absorbed through the mucous membrane into the bloodstream. It can also be absorbed through the skin as a transdermal patch for more sustained effect. M - it is metabolised quickly in the liver, and has a very short-life of around 5 minutes before it is converted to glyceryl dinitrate. If swallowed, it becomes ineffective because of first-pass metabolism.

Question 28

Give the rationale of sublingual route of GTN administration

Answer 28

When GTN goes through first pass metabolism, it will be almost completely metabolised. This means that it is made inactive following first pass metabolism. Sublingual administration allows it to have its action before metabolism.

Question 29

What is the pharmacokinetics of aspirin? use ADME

Answer 29

A - it is a dispersible/chewed tablet which will be absorbed quickly in the gut. M - it will make its ways to the liver quickly to be metabolised. As it is a pro-drug, it needs to be go through first pass metabolism to become active.

Question 30

Give rationale for the recommended dosage of aspirin for ACS

Answer 30

a higher dose of 300mg will have higher bioavailability for the antiplatelet effect

Question 31

Give examples of non-pharmacological management for ACS. Include rationale

Answer 31

1. Improve nutrition - improving diet and recommending a Mediterranean style dit and avoiding saturated fats is recommended to aid in reducing lo density lipoproteins in the blood. 2. Stop smoking - to prevent further damage to and build of atherosclerotic plaque in the coronary artery which helps lower heart rate and blood pressure. 3. Regular exercise - exercise strengthens the heart muscle which increases its efficiency and ability to pump blood. It also reduces cardiovascular risk factors such as high BP, high cholesterol and obesity which contributes to further ACS event. 4. Losing weight - obesity increases the workload on the heart, therefore maintaining weight is essential to reduce the risk of ACS.

Question 32

Give some examples of risk factors for ACS

Answer 32

- high BP - high cholesterol - smoking - diabetes - obesity - sedentary lifestyle - unhealthy diet - age, family history, gender, race/ethnicity