Theme 3: Lecture 13 - Drug treatments for CVD 3 (ischaemic heart disease)

Question 1

Describe the mechanism of action where nitrates lead to relaxation of smooth muscle

Answer 1

• Nitrates (GNT) enter cell and are broken down into nitric oxide
• NO stimulate guanylyl cyclase to convert GTP into cGMP
• cGMP stimulate myosin light chain phosphatase to remove the phosphate group from phosphorylated myosin light chain to convert it into myosin light chain
• Myosin light chain leads to relaxation of smooth muscle
• (Phosphorylated myosin light chain leads to contraction of smooth muscle due to actin myosin cross bridges)

Question 2

What are nitrates

Answer 2

A class of drugs that, when acted on by mitochondrial enzymes, will break down to generate nitric oxide

Question 3

What causes NO to be released in endothelial cells

Answer 3

• Acetyl choline, Bradykinin and shear stress stimulate entry of Ca2+ into cell
• Ca2+ stimulates NOS (nitric oxide synthase) to produce NO from L-arg

Question 4

What is the end diastolic volume (preload) regulated by

Answer 4

sympathetic system and RAAS, (contractility of venules; RAAS (Na+ and H2O retention)

Question 5

What is heart rate regulated by

Answer 5

sympathetic system and Ca2+

Question 6

What is contractility regulated by

Answer 6

sympathetic system and Ca2+

Question 7

What is the total peripheral resistance regulated by

Answer 7

sympathetic system and RAAS

Question 8

Definition of stable angina

Answer 8

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

Question 9

What is drug treatment of ischaemic heart disease designed to do

Answer 9

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

Question 10

Give an example of a nitrate

Answer 10

Glyceryl trinitrate (GTN)

Question 11

Side effects of nitrates

Answer 11

• Postural hypotension
• Headache
• Dizziness
• Reflex tachycardia

Question 12

How do nitrates increase blood supply to the heart

Answer 12

Nitrates dilate some coronary arteries increasing blood supply to the heart

Question 13

How do nitrates decrease the heart’s workload

Answer 13

• Nitrates lead to an increase in cGMP
• This leads to a decrease in Ca2+
• Leading to venodilation
• Which decreases preload
• Which reduces the heart’s workload

Question 14

Why is reflex tachycardia a side effect of nitrates

Answer 14

• Baroreceptors detect low BP in the aortic arch and coronary artery
• Activation of the sympathetic nervous system to release noradrenaline to increase HR and BP

Question 15

What should you do if treatment with nitrates causes reflex tachycardia

Answer 15

should look to block effects of sympathetic nervous system using a beta blocker, such as bisoprolol.

Question 16

How do beta blockers decrease cardiac workload

Answer 16

• They decrease the frequency and force of contraction which decreases cardiac output
• Beta blockers also inhibit renin release from kidney and so inhibit RAAS.

Question 17

Name a beta blocker

Answer 17

Bisoprolol

Question 18

Side effects of beta blockers

Answer 18

• Bronchoconstriction
• Fatigue
• Contraindicated in patients with peripheral vascular disease

Question 19

What can mixtures of calcium channel blockers and beta blockers cause

Answer 19

• severe bradycardia

- MI

Question 20

How do calcium channel blockers decrease cardiac workload

Answer 20

• Decrease the frequency of contraction
• Decrease the force of contraction
• Increase dilation of arterioles
• All of which help to decrease cardiac workload

Question 21

Which classes of calcium channel blockers decrease the frequency and force of contraction

Answer 21

Phenylalkylamines and benzothiazepines

Question 22

Which class of calcium channel blockers increase dilation of arterioles

Answer 22

Dihydropyridines

Question 23

When are calcium channel blockers used to treat ischaemic heart disease

Answer 23

In asthmatics or other groups where beta blockers are contraindicated

Question 24

Name a dihydropyridine calcium channel blocker

Answer 24

amlodipine

Question 25

Name a phenylalkylamine calcium channel blocker

Answer 25

verapamil

Question 26

Name a benzothiazepine calcium channel blocker

Answer 26

Diltiazem

Question 27

How do calcium channel blockers decrease HR

Answer 27

• 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.

Question 28

How do calcium channel blockers decrease the force of contraction of ventricles

Answer 28

They also decrease the force of contraction of the ventricles by reducing calcium entry through L-type channels.

Question 29

What are the drugs/classes of drugs used to treat ischaemic heart disease

Answer 29

• Nitrates
• Beta blockers
• Calcium channel blockers
• Ivabradine
• Long acting nitrates (isosorbide mononitrate)
• Nicorandil
• Ranolazine

Question 30

What does ivabradine do

Answer 30

• Blocks the pacemaker current (Ih/f) in the nodal tissue of the heart.
• 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 directly alter the force of contraction of the heart

Question 31

Side effects of ivabradine

Answer 31

• Luminous phenomena (Ih) in retina
• Blurred vision
• Dizziness

Question 32

Name a long acting nitrate

Answer 32

isosorbide mononitrate

Question 33

What do long acting nitrates do

Answer 33

decrease preload

Question 34

What does Nicorandil do

Answer 34

It has a dual action:

• It works like nitrates
• And also opens K+ ATP channels. This causes coronary vessels to dilate leading to increase coronary blood flow and dilates arterioles leading to decreased afterload

Question 35

What does Ranolazine do

Answer 35

Blocks the late Na+ current in the heart that becomes overexpressed in pathological conditions