Drug treatments for ischaemic heart disease

Question 1

Define ischaemic heart disease

Answer 1

Narrowing of the lumen of the coronary arteries resulting in an imbalance between the supply of oxygen (and other essential nutrients) and the myocardial demand resulting in myocardial ischaemia and chest pain

Question 2

What is the main problem of ischaemic heart disease?

Answer 2

The imbalance of oxygen supply and demand

Question 3

Name an Endothelium-derived relaxing factor

Answer 3

Nitric oxide

Question 4

Define stable angina

Answer 4

A predictable pattern of pain during exercise that is relieved by rest

Question 5

What is the function of the drug treatment used in stable angina?

Answer 5

Drug treatment designed to decrease work done by the heart and/or increase blood supply and treat risk factors.

Question 6

Name the drug treatment used in stable angina

Answer 6

Nitrates

Question 7

What is the main effect of nitrates?

Answer 7

Decrease preload by dilating the veins
They will however dilate some coronary arteries and regulated some blood supply to the heart
Have a minor effect on arterioles to increase afterload

Question 8

What are the side effects of nitrates?

Answer 8

Postural hypotension
Reflex tachycardia
Headache
Dizziness

Question 9

What is reflex tachycardia and what can be used to prevent it?

Answer 9

Reflex tachycardia due to activation of sympathetic nervous system. If treatment causes reflex tachycardia, then should look to block effects of sympathetic nervous system using a beta blocker, such as bisopolol.

Question 10

Why is reflex tachycardia an issue after giving someone nitrates?

Answer 10

The purpose of the nitrate is for the ischemic heart disease
Do not want to increase heart rate/ blood pressure

Question 11

Which receptor do beta blockers inhibit?

Answer 11

Beta 1 receptors

Question 12

What do beta blockers do?

Answer 12

Reduce frequency
Reduce force of contraction
Reduce cardiac output
Also inhibit renin release from kidney
Also inhibit RAAS
Reduce the calcium coming from L type channels

Question 13

State the side effects of beta blockers

Answer 13

Bronchoconstriction
Fatigue
Contraindicated in patients with peripheral vascular disease

Question 14

What do CA2+ channel antagonists do?

Answer 14

Decrease frequency
Decrease force of contraction
Increased dilation of arterioles
These all lead to a decrease in cardiac workload

Question 15

Describe how calcium channel blockers reduce force of contraction and reduce heart rate

Answer 15

CCBs can reduce heart beat by blocking L-type channels in the SA and AV-nodes. This will slow the rate of depolarisation and therefore reduce the rate of action potential generation. They also decrease the force of contraction of the ventricles by reducing calcium entry through L-type channels.

Question 16

What does Ivabradine do?

Answer 16

Blocks the pacemaker current (Ih/f) in the nodal tissue of the heart.

Question 17

What are the side effects of ivabradine?

Answer 17

Luminous phenomena (Ih) in retina
Blurred vision
dizziness

Question 18

Describe how ivabradine causes a decrease in cardiac rate?

Answer 18

Ivabradine will reduce Na+ entry through If channels and so slow the rate of depolarisation of the SA node cells and reduce firing frequency and therefore heart rate. It will not alter the force of contraction of the heart

Question 19

Name some alternatives to nitrates, beta blockers and calcium channel blockers for ischemic heart disease/angina

Answer 19

Long acting nitrates (isosorbide mononitrate) - Decrease preload
Nicorandil - Decreases afterload- Increases NO causing venous dilatation, opens K+ ATP channels in smooth muscle causing hyperpolarization of the muscle.
Ranolazine - Reduces work done by the heart
Trimetazidine - rebalances energy metabolism in the cell- heart muscle cells use glucose instead of fatty acids

Question 20

Describe the action of treatment to reduce hypercholesterolaemia 2o Prevention

Answer 20

Drugs designed to either inhibit uptake from GI tract or reduce production in liver.
Frontline treatment are the STATINS e.g. simvastatin, atorvastatin

Question 21

Describe the action of statins

Answer 21

Statins decrease the production of cholesterol in the liver by inhibiting the HMG CoA enzyme. This stimulates the liver cells to express LDL receptors and allows the liver cells to scavenge LDL cholesterol from the plasma. This reduces plasma LDL cholesterol levels.

Question 22

List some secondary prevention of hypercholesterolaemia and its effects

Answer 22

Aspirin - Antiplatelet agents (aspirin/clopidpgrel)
ACE inhibitors (e.g. ramipril) - Decrease the workload on the heart
ARBs (losartan) - Decrease the workload on the heart

Question 23

List the treatment for unstable angina, NSTEMI and STEMI

Answer 23

As for stable angina + antiplatelet

Aspirin; aspirin + clopidogrel (prasugrel, ticagrelor)

Question 24

Describe the mechanism of action of some key antiplatelet agents

Answer 24

Platelet activation occurs when the endothelial cells become damaged. This releases ADP which acts on P2Y12 receptors to stimulate the platelet to express GPIIb/IIIa receptors. Fibrinogen binds to these receptors to cross link different platelets. Activation of COX also helps platelet activation through the production of Thromboxane A2. Aspirin inhibits COX irreversibly.. Clopidogrel and Prasugrel are ADP antagonists and block P2Y12 receptors.

Question 25

Describe the treatment for a myocardial infarction

Answer 25

• Pain Relief - Diamorphine u-opioid receptors
  Decreases pain, anxiety, sympathetic drive, vasodilates
• Oxygen
• Aspirin/GTN
• Clot busting drugs - Tenecteplase, alteplase, streptokinase improve tissue perfusion. Stimulates the conversion plasminogen to plasmin, which breaks down fibrin
• Beta blockers - Decrease cardiac workload, prevents arrhythmias E.g. metoprolol/bisoprolol-short acting
• ACE inhibitors - Decrease cardiac workload, prevents remodelling development of heart failure E.g. Ramipril
• Anticoagulant - In case of long term bed rest, prevents thrombus formation E.g. warfarin

Question 26

What is a pro-drug?

Answer 26

A drug which becomes active only in the body

Increases the drugs bioavailability

Question 27

Describe the action of digoxin

Answer 27

Digoxin binds to the Na+/K+ ATPase and inhibits its action. This will increase levels of Na+ ions inside the heart muscle cells. This increase will in turn inhibit the Na+/Ca2+ exchanger which will lead to a build up of Ca2+ inside the muscle cell and a stronger contraction

Question 28

Describe the action of Amiodarone

Answer 28

K+ channel blocker that increases the refractory period of ventricular myocytes and can terminate arrhythmias

Question 29

What is Amiodarone used for?

Answer 29

Treatment of dysrhythmias

Question 30

What is the cause of the symptoms of a heart attack?

Answer 30

Activation of the sympathetic nervous system and this increases noradrenaline/adrenaline

Question 31

What is digoxin used to treat?

Answer 31

Heart failure

Question 32

Why does digoxin have a narrow therapeutic index?

Answer 32

Blocks the sodium potassium pump which is vital to life