L5- Angina

Question 1

What are the factors affecting the hearts energy status and viability?

Answer 1

1. Coronary artery blood flow
2. Sympathetic nerves (+/- heart rate)
3. Peripheral arterioles (provide vascular resistance known as afterload against which the ventricles pump blood)
4. Central venous pressure (preload sets resting ventricular pressure and ionotropic state)

Question 2

What increases the energy supply to the heart?

Answer 2

Increased coronary blood flow

Question 3

What decreases the energy demand of the heart and why?

Answer 3

Reduced afterload or preload

Negative ionotropy

Question 4

What is angina pectoris?

Answer 4

It is a symptom of ischaemic heart disease where chest pain occurs due to reduced blood flow to the heart via the coronary arteries.

Question 5

What causes angina pectoris?

Answer 5

Due to the effects of reduced coronary flow

Insufficient supply of glucose, O2 and other nutrients

Insufficient removal of metabolic products e.g adenosine (ATP metabolism product) accumulation due to failure of washout
Cause activation of local nerves to generate chest pain

Question 6

What is the significance of theophylline?

Answer 6

It was used to antagonise the action of adenosine to relieve chest pain. But also causes increases in heart rate and contractility so was stopped.

Question 7

What are the 3 types of angina?

Answer 7

1. Stable- Fixed partial block of coronary artery (atheroma), exercise causes pain and rest alleviates it.
2. Unstable- When the atheroma fissures and forms a thrombus which may fully block the coronary artery. Associated with acute MI.
3. Inappropriate coronary vasospasm (rare)- coronary arteries appear normal but spontaneously go into spasm.

Question 8

What is the symptomatic treatment of an acute angina attack?

Answer 8

Sublingual GTN which relieves symptoms via venodilation which reduces central venous pressure (preload)

This reduces the left ventricular diastolic tension and reduces ionotropy and oxygen demand.

Question 9

What are the clinical features of stable angina?

Answer 9

Coronary supply meets demand at rest.
Coronary response to exercise (and increase in ventricular work) is is vasodilation.
But an atheroma cannot dilate so the diameter of the vessel (where the atheroma is) remains the same in rest and exercise.

Question 10

Why is coronary dilation not a mechanism for treating stable angina?

Answer 10

Atheroma cannot dilate
Dilating other parts of the diseased artery will not increase blood flow as it is the atheroma that causes the limitation

Question 11

How is stable angina diagnosed?

Answer 11

Exercise induced chest pain

ST segment elevation in the ECG during exercise which reverses slowly at rest

Question 12

What are the drugs used for prophylaxis in stable angina?

Answer 12

1. Long acting nitrates
2. Calcium antagonists
3. Beta blockers
4. Ivabradine
5. Trimetazidine

Question 13

How are long acting nitrates used for prophylaxis?

Answer 13

Selective reduction of preload by acting on capacitance vessels (veins)
Also act on arterioles but it is a small effect, overcome by sympathetic nerves
Tolerance develops quickly but is overcome by intermittent dosing

Question 14

What are the long acting nitrates?

Answer 14

Erythrityl tetranitrate
Isosorbide dinitrate
Pentaerythritol tetranitrate

Question 15

What is the molecular and cellular mechanism of nitrates?

Answer 15

De-nitrated in blood stream to produce NO
NO diffuses into smooth muscle and initiates a cascade involving GMP
End result is smooth muscle relaxation

Question 16

What are the calcium antagonist drugs?

Answer 16

Verapamil, Diltiazem, Amlodipine, Nifedipine

Question 17

How do calcium antagonist drugs achieve prophylaxis?

Answer 17

Produce selective reduction of afterload (act on arterioles)
Verapamil and diltiazem may also have negative ionotropic effects
Both effects reduce ventricular work

Question 18

What is the molecular mechanism of calcium antagonists?

Answer 18

All block Ca2+ entry into cells by blocking L type calcium channels.
Block via slow inward current and cell contraction
In vessels= vasodilation (all)
In heart= negative ionotropy (verapamil and dilitiazem)

Question 19

How do beta blockers achieve prophylaxis?

Answer 19

Non-selective beta or selective beta-1 adrenoceptor agonists have negative chonotropic (SAN) and ionotropic (ventricular muscle) effects.
Reduce cardiac energy consumption to reduce chest pain.

Question 20

How does Ivabradine achieve prophylaxis?

Answer 20

Relatively selective for slowing SA node rate

It blocks the funny current (If) which slows down the heart rate

Question 21

How does Trimetazidine achieve prophylaxis?

Answer 21

Emerging drug
Main form of ATP synthesis in the heart is fatty acid oxidation
The drug blocks the production of fatty acids so ATP production switches to glycolysis which reduces O2 demand.

Question 22

What are the drugs used in unstable angina?

Answer 22

Nitrates, calcium channel blockers and beta blockers indirectly reduce pain
Aspirin is used as an antithrombotic

Question 23

How is variant angina treated?

Answer 23

Only form of angina that can be treated using vasodilation due to the angina being caused by a spasm in the artery (otherwise the artery is healthy)