Cardiovascular pharmacology 2

Question 1

What are the endogenous mechanisms of positive inotropes?

Answer 1

• increase contractility
• sympathetic stimulation
• increase EDVV by increasing preload

Question 2

How can we create the effect of positive inotropes pharmacologically?

Answer 2

• mimic/enhance sympathetic activity

- increase intracellular calcium

Question 3

Which 3 drug groups are used to act as positive inotropes?

Answer 3

• PDE III inhibitors
• Sympathomimetics
• Cardiac glycosides

Question 4

What happens when phosphodiesterase is inhibited?

Answer 4

Increase in intracellular cAMP (as it usually degrades it)

This leads to increased contractility

Question 5

What effect will increased intracellular cAMP have in the cardiac myocyte?

Answer 5

• Activated protein kinase A
• This phosphorylates Ca channels, making them more likely to open
• Increased flow of Ca into cardiomyocyte + increased Ca induced Ca release
• Stronger contraction

Question 6

What are the two other predictable effects of increased intracellular cAMP?

Answer 6

• Vasodilation: because of activated myosin light chain kinase
• Tachycardia: faster Ca flow into cell = faster depolarisation

Question 7

Which PDE III inhibitor is used in practice, how is it administered?

Answer 7

Pimobendan

• Positive inotrope and vasodilator
• Oral or parenteral administration

Question 8

What is the only cardiac glycoside in use?

Answer 8

Digoxin

Question 9

What is the theory of the supposed positive inotropic effect of Digoxin?

Answer 9

• Inhibits the Na/K pump in cardiac myocytes which increases the intracellular Na
• Reduced Ca extrusion from the cell because there is a smaller gradient for Na to move into the cell
• Therefore more Ca moved into SR to be released during an action potential

Question 10

By inhibiting Na removal from the cell, what other effect do you predict cardiac glycosides to have in the heart?

Answer 10

Negative chronotropy - major action of these drugs

Question 11

What is the target of sympathomimetics?

Answer 11

β1 receptors on cardiac myocytes - agonist action will increase contractility

Question 12

What are the three types of negative inotropes?

Answer 12

• Sympathetic antagonists
• Cholinergics
• Calcium channel blockers

Question 13

A drug affecting perfusion will alter which 3 factors?

Answer 13

• CO
• Vascular diameter
• Circulating volume

Question 14

Drugs affecting arterial pressure will alter which 2 factors?

Answer 14

• CO

- TPR

Question 15

Why would we want to reduce preload?

Answer 15

Reduce congestion
Reduce oedema
Reduce work for the heart

Question 16

Why would we want to reduce afterload?

Answer 16

Forward HF
Vasodilation
Reduce congestion

Question 17

Why would we want to reduce systemic arterial pressure?

Answer 17

• Reduce afterload

- Organ failure will occur if there is chronic hypertension so this needs to be reduced

Question 18

What are the 4 direct vasodilators?

Answer 18

• Nitrates
• Ca channel blockers
• PDE III inhibitors
• Hydralazine

Question 19

Describe the effects of nitrates

Answer 19

• Cause peripheral vasodilation via nitric oxide action

- Leads to vasculature relaxation

Question 20

Which 2 nitrates are used in practice?

Answer 20

• Nitroprusside

- Nitroglycerine

Question 21

Ca channel blockers work as direct vasodilators, but are also in which other drug group?

Answer 21

Class IV antidysrhythmics

Question 22

Describe the action of PDE III inhibitors

Answer 22

Used for chronic heart failure.

• Inhibit the breakdown of cGMP
• This activated protein kinase G
• This activates myosin light chain phosphatase
• Dephosphorylates myosin light chain which causes relaxation

Question 23

Hydralazine acts as a …?

Answer 23

Arteriodilator

Question 24

What are the 2 indirect vasodilators and through what method do they act?

Answer 24

• Sympathetic NS
• RAAS
• Extrinsic mechanism

Question 25

Where do sympathetic antagonists act?

Answer 25

- non-specific | - can act at any point from the brainstem to peripheral receptors

Question 26

What are the 2 sympathetic antagonists used in practice?

Answer 26

- Prazosin | - Phenoxybenzamine

Question 27

What 2 bits of the RAAS cause vasoconstriction?

Answer 27

- Angiotensin II | - Stimulated ADH release

Question 28

What else does the RAAS do that influences blood pressure and preload?

Answer 28

At the kidney it retains water and sodium ions

Question 29

Which 3 conditions would benefit from RAAS blockade?

Answer 29

- Chronic heart failure - Hypertension - Chronic renal failure

Question 30

What is the role of ACE?

Answer 30

Converts Angiotensin I to Angiotensin II

Question 31

What do ACE inhibitors cause?

Answer 31

- Vasodilation - Reduced circulating volume - Thus, improved tissue perfusion - Reduced preload - Reduced systemic arterial pressure

Question 32

Where are ACE inhibitors activated?

Answer 32

Liver

Question 33

What are Aldosterone antagonists used for?

Answer 33

- Reduce retention of sodium and water, which also reduced K loss - Reduced cardiac remodelling which is associated with aldosterone

Question 34

What are the 2 aldosterone antagonists used in practice?

Answer 34

- Spironolactone | - Cardalis (Benazepril + spironolactone)

Question 35

What other method can be used to reduce preload?

Answer 35

Diuretics