Cardio renal L9

Question 1

how might angina feel to a patient

Answer 1

This describes the severe, suffocating chest pain that is characteristic of an attack of angina

Question 2

where is angina often refered to

Answer 2

s ‘referred’ to the left shoulder and upper arm and sometimes the teeth8.

Question 3

wen does blood perfuse the myocardium?

Answer 3

The coronary circulation thus is unusual, because during systole, the myocardium receives little blood (and so oxygen) supply, but blood does perfuse the myocardium during diastole.

Question 4

why does symapthetic stimulation predispose angina suffereds to pain?

Answer 4

1. Increases heart rate, reducing the proportion of the time the heart is in diastole and thus capable of being perfused.
2. Increases force of contraction (and thus oxygen demand).
3. Deceases cardiac efficiency (more oxygen used to perform the same mount of work).

Question 5

angina is normally primarily a result of…

Answer 5

Normally primarily as a result of occlusion of coronary arteries by fatty deposits and secondarily by subsequent pathological changes to the arteries

Question 6

T or F

Anything that predisposes the heart to work reduces its capacity for perfusion and can result in angina

Answer 6

T

Question 7

which is normal and which is angina?

Answer 7

Question 8

for people who suffer from angina - may there be no more capacity - aka the arterioles are already amximally dilarted?

Answer 8

yep - so when demand increases - the heart cannot supply

Question 9

During exercise there may be no additional capacity for dilatation and so the myocardium becomes ischaemic leading to …

Answer 9

During exercise there may be no additional capacity for dilatation and so the myocardium becomes ischaemic leading to the characteristic anginal pain

Question 10

People with ischaemic heart disease develop ….. what to help them cope?

Answer 10

People with ischaemic heart disease develop collateral blood vessels to help the myocardium to cope

Question 11

Individuals with ischaemic heart disease develop collateral blood vessels as a response to the poor perfusion. This phenomenon is known as ______.

Answer 11

Individuals with ischaemic heart disease develop collateral blood vessels as a response to the poor perfusion. This phenomenon is known as angiogenesis.

Question 12

give some classes of druges used to treat angina?

Answer 12

• Nitrovasodilators
• ß-adrenoceptor blockers
• Ca2+-channel blockers
• If-blocker
• Inhibition of the late Na+ current

*

Question 13

describe how nitrovasodilators can treat angina?

Answer 13

• include glyceryl trinitrate9, isosorbide mononitrate and amyl nitrite
• they are converted to NO in vascular smooth muscle cells
• cause venous dilitation - reducing central venous filling pressure - and preload
• also operate on the collaterals in chronic angina patients - mainly in ischaemic areas, not affecting dilitation in well perfused areas

Question 14

Glyceryl trinitrate- how is it administereed?

Answer 14

Glyceryl trinitrate is poorly absorbed from the stomach and so it is taken sublingually (where it is absorbed directly into the systemic circulation)

Question 15

nitrovasodilators:

They include glyceryl trinitrate, isosorbide mononitrate and amyl nitrite.

The first two of these are commonly used to treat ……

The third is a ….

Answer 15

They include glyceryl trinitrate9, isosorbide mononitrate and amyl nitrite. The first two of these are commonly used to treat angina, the former especially in acute attacks. The third is a non-therapeutic recreational drug

Question 16

describe coronary steal?

Answer 16

Other vasodilator drugs, such as dipyridamole (which stimulates adenosine receptors) open all vessels (not only in ischaemic, but also in well oxygenated tissues) and diverts the blood away from the ischaemic region. This phenomenon is known as ‘coronary steal’.

Question 17

describe how Beta blockers are used to treat angina

Answer 17

• ß-blockers like bisoprolol and atenolol (ß1 antagonists) reduce the effects of sympathetic stimulation that normally occur in the heart
• decrease BP - decreasing afterload
• Coronary blood vessels also have ß2 receptors (which normally cause vasodilatation) and also á1 receptors that produce vasoconstriction.
• Normally the á response is overwhelmed by the ß2 response, but non- specific ß-antagonists inhibit this, and unmask the á1-mediated constriction.
• In heart failure (which frequently occurs concurrently with angina) it is necessary to maintain sympathetic stimulation to produce an adequate cardiac output.
• Hence Beta blockers arent always great for heart failure - as sympathetic stimulation is required to maintain adequate CO

Question 18

describe how Ca2+-channel blockers are used to treat angina

Answer 18

• dihydropyridines - block Ca2+ entry to smooth muscle
• causes vasodilation
• decreasing BP
• decreasing afterload
  *

Question 19

most commonly used dihydropyridine for treating angina?

Answer 19

Amlodipine

Question 20

why do dihydropyridines work on vascular smooth muscle in preference to cardiac Ca2+ channels?

Answer 20

The answer lies in the low resting potential (-50 to -60 mV) of vascular smooth muscle.

This means that more channels remain inactivated than in cardiac muscle (with a resting potential of -80 to -90 mV) and dihydropyridines bind to the inactivated form of the channel.

Question 21

how are funny current blockers used to treat angina?

Answer 21

• eg: ivabradine
• blocking If reduces pacemaker activity
• slows heart rate
• improves perfusion of the myocardium
• helps people with stable angina
• It is normally only used when ß-blockers or Ca2+-channel blockers are inappropriate - eg heart failure

Question 22

what is stable angina?

best drug ?

Answer 22

angina due to exercise

these patients often have avery high heart rates

ivabradine may be appropriate

Question 23

where in the heart is ivabradine selective to>

Answer 23

Because of the location of the HCN channels upon which ivabradine acts, its effects are selective to the sinus node and ivabradine has no effect on intra- cardiac conduction, myocardial contractility or ventricular repolarisation

Question 24

describe how Inhibition of the late Na+ current can help in the treatment of angina

Answer 24

• drug eg: ranolazine
• inhibits the late phase of the Na current in cardiac myocytes
• in ischaemic myocardium - late Na current leads to climbing calcium levels (thorhg NaCa exchanger)
• leads to impaired relaxation
• poor cardio perfusion
• Blocking late INa means Ca2+ overload and diastolic wall stress are reduced, leading to improved coronary blood flow.

Question 25

Answer 25

Question 26

is reperfusion injury applicable to hte heart after ischaemia?

Answer 26

yes

Question 27

describe ischaemic preconditioning

Answer 27

It is now known that several short periods of ischaemia (e.g. three 5 minute occlusions of the blood supply separated by 5 minutes reperfusion) increase the ability of the heart to withstand longer periods of ischaemia - this is called ‘ischaemic preconditioning’ and it provides an inherent ability of the myocardium to protect itself from ischaemic damage.

Question 28

describe nicorandil:

what does it do?

whens it used?

Answer 28

Similar protection can be stimulated (it seems) by use of the K_ATP-opening drug, nicorandil, which can be used in angina.

Question 29

T or F

The exact mechanisms involved in ischaemic preconditioning are poorly understood

Answer 29

T

Question 30

describe how the mitochondrial permeability transition pore (MPTP) is involved in ischaemia reperfusion injury

Answer 30

1. MPTP (large non selcetive pore) opens in mitochrondrial membrane (was closed during ischaemia - opens during reperfusion)
2. pore is opened by high mitochondrial [Ca2+], oxidative stress, ATP depletion and mitochondrial depolarisation, which are all present during reperfusion
3. uncoupling of the respiratory chain, ultimately resulting in ATP depletion and generation of reactive oxygen species (ROS)
4. leadsto necrosis and matrix swelling = apoptosis

5.

Question 31

Answer 31

Question 32

in ischaemic preconditioning, what triggers teh end effector pathways for protection?

Answer 32

A mitochondrial ATP-sensitive potassium channel (mitoKATP) seems to trigger as the end-effector of ischaemic preconditioning and protection.

Question 33

2 methods we can Revascularisation of the coronary arteries

Answer 33

Revascularisation can be achieved by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)

Advances in angioplasty have increased the success rate of this technique and there has been a year-on-year rise in the use of PCI

Question 34

is CABG on the fall?

Answer 34

yesss. stents are favourable now

Question 35

describe the new stents - what probelsm ahve tey overcome?

Answer 35

new stents prevent recoil of the artery wall

inhibit the development of neointimal proliferation

hey are coated with a polymer within which are embedded antiproliferative drugs. These leach out into the wall of the vessel over the first few weeks after the placement of the stent and have a significant effect in reducing the incidence of restenosis

These drugs (such as sirolimus and paclitaxel) leach out into the wall of the vessel over the first few weeks after the placement and reduce the incidence of restenosis

Question 36

fat

Answer 36

mamba