PHAR232 - Pharmacological tools in HF 1

Question 1

What are key things that SNS does on the cardiovascular system?

Answer 1

• Increase HR
• Vasoconstriction
• Increase contraction force
• Activate RAAS

Question 2

In RAAS, what is the major vasoconstrictors?

Answer 2

Angiotensin II
Aldosterone = increased H20 retention = Increase BP

Question 3

Heart failure

Question 4

What is forward heart failure?

Answer 4

Inability of heart to pump blood FORWARD to meet metabolic demands of body

Question 5

What is backward heart failure?

Answer 5

Cardiac pressure too high

Thick blood
(thick smoothie, causes straw issues)

Question 6

Heart failure pathophysiology revision

Answer 6

Question 7

Wha happens with a reduction in baroreceptor integrity on HR?

Answer 7

• Blunts PNS activity
• Increased constant HR
• Increased vascular tone
• Increased heart overload

Question 8

What are catecholamines?

Answer 8

NA and adrenaline

Question 9

How much higher is NA in CHF patients?

Answer 9

2-3x

Question 10

What is the number 1 vasoconstrictor ?

Answer 10

Angiotensin II
+ increases NA + aldosterone

Question 11

What does aldosterone do?

Answer 11

Holds H20 = increase BP

Question 12

Revision

Question 13

Is nitric oxide a vasodilator or vasoconstrictor?

Answer 13

Vasodilator

Question 14

What is the number 1 vasodilator in the cardiovascular system?

Answer 14

Nitric oxide
Purpose = decrease Ca++

Question 15

What is eccentric (elongated) myocardial hypertrophy due to?

Answer 15

Volume overload
- Insufficient muscle to contract around increased volume

Question 16

What is concentric (compact) myocardial hypertrophy de to?

Answer 16

Excessive muscle
- Compromises ventricular capacity
- Causes inefficient contraction

Question 17

What are 2 extremely key treatment interventions for HF?

Answer 17

• B1 adrenergic receptors e.g. beta blockers
• Angiotensin II type 1 receptor (AT1R) e.g. ACE inhibitors

Question 18

What is the rationale for b1 ad receptors?

Answer 18

Overexcitation of SNS accompanies by electated ciruclating catecholamines

Question 19

What does increased HR do to blood volume?

Answer 19

Reduces capacity to fill
= low BV

Question 20

B1 adrenergic receptors info - KNOW

Question 21

What is the goal for b1 adrenergic receptor blockers?

Answer 21

Block B1 receptors in heart
- REduce HR
- Optimise contraction force

Question 22

What are ischaemic heart diseases?

Answer 22

Angina
Coronary artery disease

Question 23

Problem with beta blockers in HF

Answer 23

Question 24

What does decreased HR do to end diastolic volume (EDV)?

Answer 24

Increases

Question 25

What are the only beta blocker drugs (3 key ones) with vasodilatory effects effective for HF?

Answer 25

Carvedilol Bisoprolol Metoprolol

Question 26

Can you be an agonist without causing a shape change?

Answer 26

No an agonist will always cause a shape change

Question 27

Special beta blockers

Answer 27

Use of beta blockers in heart failure

Question 28

Goal = improve myocyte Ca++ availability and utilisation - Improves LV remodelling - Improvement of ion channels - Improved heart sensitivity to SNS activation = improvement in overall heart function = Improved cardiac output (CO)

Answer 28

MUST KNOW THIS SLIDE!!!!!

Question 29

Adrenergic receptors as research targets

Answer 29

Question 30

Microscopic review of myocytes after NA exposure

Answer 30

Hypercontraction association with increased cAMP

Question 31

What does long term NA do to myocytes?

Answer 31

Excitotoxicity kills cells

Question 32

Catecholamines as growth factors

Question 33

What does PLC create?

Answer 33

IP3 = increase Ca++ DAG = activates PKC

Question 34

What is MAPK associated with?

Answer 34

growth

Question 35

What does CREB stand for?

Answer 35

CAMP Response Element Binding Protein

Question 36

What does CREB do?

Answer 36

Frasciliates transcription and supression of genes

Question 37

What does CREB do when it's become phosphorylated?

Answer 37

Dimerises Binds to cAMP response element on DNA Regulates RNA transcription Controls number and identity of proteins in cells

Question 38

Catecholamines as growth factors

Answer 38

Potential mechanisms underlying value of special beta blockers

Question 39

Where is angiotensin-converting enzyme found (ACE)

Answer 39

Lungs

Question 40

Role of ACE

Answer 40

ACE = increases bradykinin = increases NO release = increases prostaglandins Too much vasodilation = other enzymes creating ACE

Question 41

Blocking ACE = increased bradykinin

Answer 41

Angiotensin II and it's receptors

Question 42

What type of receptor is angiotensin II, type 1 receptor (AT1-Rs)

Answer 42

GPCR

Question 43

what does (AT1-Rs) stand for?

Answer 43

angiotensin II, type 1 receptor

Question 44

Quetions regarding AngII

Answer 44

review and understand why has B-arrestin -

Question 45

Abbreviation definitions

Question 46

What's hyperplasia?

Answer 46

- increase in the NUMBER of cells in a tissue or organ, = enlargement. = cell PROLIFERATION.

Question 47

What's hypertrophy?

Answer 47

- Increased Myocyte Growth - increase in the SIZE of EXISTING cells, but not the number of cells.