L7- Heart failure

Question 1

What are the adverse consequences of heart failure?

Answer 1

• Impaired cardiac output leads to activation of renin-angiotensin system
• This leads to sodium retention
• This causes reduced diuresis
• This leads to high venous pressure
• Causes oedema

Question 2

What are the 3 main causes?

Answer 2

1. High resistance to cardiac output (afterload) due to aortic stenosis or arterial hypertension so less blood ejected per heartbeat.
2. Heart valves not closing properly leads to less blood being available to eject per beat
3. Heart muscle disease e.g cardiomyopathy leads to less blood ejected per heartbeat

Question 3

What are the principles of treatment of heart failure?

Answer 3

• Relieve underlying condition (replace valve, etc)
• Relieve aggravating conditions (e.g. anaemia)
• Reduce central venous pressure (preload) to reduce
oedema
• Increase cardiac output (positive inotropes) to
reduce skeletal muscle fatigue
• Reduce resistance to cardiac output (vasodilatation)
to reduce skeletal and cardiac muscle fatigue

Question 4

What are the drug treatments for heart failure?

Answer 4

• Positive ionotropes
• Drugs that reduce central venous pressure (preload)
• Drugs that reduce afterload
• Drugs that reduce afterload and preload
• Angiotensin II receptor blockers
• B1 antagonists

Question 5

What are positive ionotropic drugs?

Answer 5

Cardioglycosides
B1 agonists
Phosphodiesterase inhibitors

All increase intracellular Ca2+ concentration which stimulates force of heart muscle contraction

Question 6

How do cardioglycosides work?

Answer 6

Inhibition of Na/K ATPase causes increased intracellular Na.

This inhibits Na/Ca exchange allowing more Ca to be trapped inside the cell. (reduces Ca escape doesnt prevent it)

Question 7

How do B1 agonists work?

Answer 7

Activate cardiac B1 receptors
Activate adenylyl cyclase which increases synthesis of intracellular cAMP
cAMP inhibits inactivation of the slow inward current causing an increase in intracellular Ca

Question 8

How do PDE inhibitors work?

Answer 8

Inhibit metabolism of cAMP and cAMP inhibits inactivation of the slow inward current
Causes an increase in intracellular calcium
e.g Milrinone, Enoximone

Question 9

What does the Frank-Starling curve show?

Answer 9

The more the heart is stretched (the greater the LVEDP) the stronger the contraction (the greater the CO)

Question 10

What are drugs that reduce central venous pressure (preload)?

Answer 10

Venodilators

Diuretics

Question 11

How do venodilators work?

Answer 11

They dilate the central veins and reduce venous pressure. This may reduce oedema. e.g Nitroprusside and glyceryl trinitrate.

However vein dilation may reduce LVEDP causing decrease in CO so only used with positive ionotropic drugs.

Question 12

How do diuretics work?

Answer 12

Decrease blood volume so blood pressure is reduced.

e.g. ferosemide and spironactolone

Question 13

What are the drugs that reduce afterload and how do they work?

Answer 13

Arteriolar dialators cause a reduction in muscle fatigue.
Cause direct arteriolar dilatation which is mediated by an increase in cGMP and a fall in Ca2+

e.g hydralazine

Question 14

What are the drugs that decrease both preload and afterload?

Answer 14

Reduce oedema and muscle fatigue
e.g. Prazosin is an A1 adrenoceptor antagonist that blocks vaso/venoconstrictor effects of adrenaline and noradrenaline

e.g. Captopril, Ramipril, Enalapril block ACE enzyme so there is less AT2 which is a vaso/venoconstrictor, also decreases blood volume

Question 15

How do AT2 receptor blockers work and what are they?

Answer 15

Losartan, Valsartan, Candesartan
Less activation of receptors by AT2 so less constriction and lower blood volume
No cough like with ACE inhibitors