Angina treatment

Question 1

Characteristic distribution of angina pain

Answer 1

chest, arm, jaw
brought on by exertion, cold or excitement
chemical factors that cause pain in skeletal muscle may be responsible (K, H, adenosine)

Question 2

Two types of treatment for angina (general)

Answer 2

reduce chest pain symptoms

prolong survival

Question 3

What is the coronary window?

Answer 3

during diastole, where the coronary arteries are filing.

The aortic pressure > ventricular pressure.

Question 4

3 things that shrink the coronary window

Answer 4

1. shortening diastole (increased HR)
2. increased ventricular end diastolic pressure (eg. progressive decline in ventricular emptying, aortic stenosis)
   If cannot eject properly, will have residual blood in ventricles: higher blue line.
3. reduced diastolic arterial pressure (eg. mitral or aortic valve incompentence, heart failure) ie. if backflow of blood into ventricles due to valve rather than into resistant small artery system.

Question 5

How do we match tissue demand (exercise) to blood flow

Answer 5

by altering flow at arteriolar level
This is achieved by metabolic control: muscle cell produces byproducts (eg. adenosine) which triggers relaxation of vascular smooth muscle cells

Question 6

• Neural vasoconstrictors
• Hormonal vasoconstrictors (3)
• Local vasoconstrictors

Answer 6

• sympathetic nerves
• adrenaline, angiotensin 2, vasopressin
• myogenic response, endothelin 1

Question 7

• 2 hormonal vasodilators

- Local vasodilators

Answer 7

• acetylcholine, atrial-natriuretic peptide (ANP)

- K, CO2, H+, decreased O2, adenosine, NO, bradykinin

Question 8

Coronary ischaemia is usually the result of which process?

Answer 8

atherosclerosis (which then causes angina)

Question 9

Sudden ischaemia is usually caused by which process?

Answer 9

Thrombosis (which then may result in cardiac infarction)

Question 10

Aside from coronary ischaemia, what can also cause angina?

What is this called?

Answer 10

coronary spasms

variant angina

Question 11

Following ischaemia, what happens in terms of calcium levels?

Answer 11

get cellular calcium overload.

may cause cell death and dysrhythmias

Question 12

3 Classes of angina

Answer 12

1. Variant Angina (vasospasm - is a supply ischaemia)
2. Chronic stable angina (fixed stenosis - is a demand ischaemia)
3. Unstable angina (thrombus - is a supply ischaemia)

Question 13

How do antianginal drugs work?

2 broad types

Answer 13

to decrease the metabolic demand of the heart

Organic nitrates, nicorandil and Ca antagonists are vasodilators (decrease preload or afterload)

Beta-blockers and ivabradine slow down the heart (decrease metabolic demand of muscle)

Question 14

Preload determined by

Answer 14

the venous pressure

venous return to the heart (end-diastolic pressure/volume)

Question 15

Afterload determined by

Answer 15

aortic or pulmonary artery pressures

Question 16

Action of beta-blockers

2 examples

Answer 16

• decrease cardiac oxygen consumption by SLOWING THE HEART
  [They are blocking ability of sympathetic NS via B1 adrenogenergic recetors to modulate activity of F-type Na channels]
• also have antidysrhythmic action

Eg. bisoprolol, atenolol

Question 17

Action of calcium antagonists

Answer 17

1. prevent opening of voltage-gated L-type calcium channel
   - therefore block Ca entry
   - (inhibits Ca entry upon muscle cell depolarisation)
2. vasodilator effect mainly on resistance vessels (reduces afterload)

Question 18

2 Types of calcium antagonists

Answer 18

1. Dihydropyridine derivatives eg. amplodipine and lercanidipine
2. Rate-limiting eg. verapamil, diltiazem.
   These allow less Ca to come in each time a muscle contracts, reducing workload.

Question 19

Why are calcium antagonists important in treatment of variant angina?

Answer 19

as they dilate the coronary vessels

Question 20

Which calcium antagonists can reduce and impair AV conduction and myocardial contractility

Answer 20

rate-limiting: verapamil/diltiazem

Question 21

Main drivers at different stages of myocardial depolarisation

Answer 21

(pi like)
upshoot driven by Na
plateau phase driven by calcium
repolarisation driven by K

Question 22

Describe SA node depolarisation (neuronal).

Answer 22

Phase 1: gradual drift increase in RMP due to increase Na as funny-type Na channels open (and decrease in K as K channels slowly close). This oscillating flux of Na into cell provides pacemaker potential.
Transient Ca channels help with the final push

Phase 2: moderately rapid depolarisation due to Ca entry via slow L channels

Phase 3: rapid repolarisation as elevated internal Ca stimulates opening of K channels, and get increase in K

Question 23

What keeps the SA node rate down?

Answer 23

parasympathetic NS

through AV node

Question 24

What calcium antagonist would you use in a patient with heart failure?

Answer 24

Dihydropyridine derivatives eg. amplodipine and lercanidipine

Question 25

If using a beta-blocker, which calcium antagonist type would you avoid using?

Answer 25

Rate-limiting: diltiazem or verapamil | also contraindicated in HF, bradycardia, AV block

Question 26

Side effects of calcium antagonists

Answer 26

headache, constipation, ankle oedema

Question 27

Antidysrhythmic using calcium antagonist

Answer 27

Verapamil - slows ventricular rate in rapid AF - prevents recurrence of supraventricular tachycardia - no effect on ventricular arrhythmias

Question 28

How does GTN spray work?

Answer 28

Glyceryl trinitrate is a vasodilator. IS metabolised to NO and relaxes smooth muscle - Acts on veins to decrease preload - In higher concentrations, can affect arteries and decrease afterload - dilates collateral coronary vessels decreasing cardiac workload. This is particularly useful in variant angina

Question 29

Organic nitrate not GTN

Answer 29

Isosorbide mononitrate

Question 30

How do endothelial cells regulate vascular tone?

Answer 30

if shearing stress to endothelial cell - causes NO production, which acts on soluble gyanylate cyclase enzyme in smooth muscle, which acts to convert GTP -> GMP to cause relaxation

Question 31

K Channel Activator

Answer 31

Nicorandil - combines activation of KATP channels with nitrovasodilator actions - arterial and venous dilator

Question 32

Give 4 conditions where you might use organic nitrates

Answer 32

1. stable angina (prevention with GTN, or isosorbide mononitrate long before exercise) 2. unstable angina (IV GTN) 3. acute heart failure (IV GTN) 4. chronic heart failure (isosorbide mononitrate with HYDRALAZINE in patients of African American origin)

Question 33

Action of Ivabradine

Answer 33

inhibits f-type channels in the heart | reduces cardiac pacemaker activity (inhibits heart rate)

Question 34

Action of Ranolazine

Answer 34

unique anti-anginal used as last resort