LV dysfunction and heart failure 2

Question 1

When is RAAS and the SNS stimulated?

Answer 1

When cardiac output drops, either due to:
blood loss
heart failure

Question 2

Whats the renin-angiotensin-aldosterone system?

Answer 2

Angiotensinogen->RENIN-> Angiotensin 1-> ACE-> Angiotensin 2-> salt retention thru aldosterone release & vasoconstriction
angiotensin 2 is synergistic with the SNS- promotes the release of noradrenaline from nerve endings

Question 3

What does the sympathetic nervous system do?

Answer 3

Releases noradrenaline-> vasoconstriction (leading to peripheral resistance) and increased cardiac output
also synergistic with RAAS- promotes the release of renin

Question 4

How do changes in RAAS and the SNS benefit us when we lose blood?

Answer 4

tachycardia- increased CO
positive inotropic effect- increased CO
vasoconstriction- increased blood pressure- maintain flow
sodium and water retention- increased circulatory volume

Question 5

How do changes in RAAS and the SNS make it worse when we have heart failure?

Answer 5

Tachycardia- increased workload and oxygen demand
positive inotropic effect- “ “
vasoconstriction- increase afterload
sodium and water retention- increased preload and oedema
chronic adrenergic stimulation- myocyte toxicity and arrhythmia

Question 6

What are the main types of treatment for heart failure?

Answer 6

Diuretics
vasodilators 
aldosterone antagonists 
ACE inhibitors 
ARB- angiotensin 2 receptor blocker 
beta blocker- interferes with SNS and thus noradrenaline production

Question 7

What effects do ACE inhibitors have and when are they used? Examples of ACE inhibitors

Answer 7

Reduce mortality significantly 
-hypertension
-heart failure
-diabetic nephropathy
ramipril, enalapril, perindopril, trandolapril

Question 8

What are ACE inhibitors adverse effects?

Answer 8

Related to angiotensin 2-
hypotension 
acute renal failure 
hyperkalemia 
teratogenic effects in pregnant women
related to kinins-    
cough- dry and persistent
rash
anaphylactic reactions

Question 9

Why do ACE inhibitors increase kinin levels?

Answer 9

ACE catalyzes the conversion of bradykinin to inactive peptides
inhibiting ACE means you potentiate the effects of bradykinin

Question 10

What effects do beta blockers have and when are they used? Examples of beta blockers

Answer 10

reduce mortality (carvedilol, bisoprolol and metaprolol)
can also improve the chances of developing HF or having an event & being hospitalized
angina
heart failure
arrhythmias
hypertension
propanolol, atenolol, nadolol

Question 11

How are beta blockers selective?

Answer 11

Either beta 1 selective or non selective (both beta 1 and 2)
increase the dose of the drug- becomes non selective
selectivity is relative rather than absolute

Question 12

Why is the term cardioselective beta 1 incorrect?

Answer 12

up to 40% of the receptors in the heart are beta 2 receptors

thus cardioselective technically means beta 1 and 2

Question 13

What are beta blockers main adverse effects?

Answer 13

central NS effects:
fatigue, headache, sleep disturbance, nightmares, depression
vascular effects:
bradycardia, hypotension, cold peripheries, erectile dysfunction, worsening of asthma or COPD, PVD-claudication or Raynauds

Question 14

How can beta blockers cause heart failure?

Answer 14

When the heart is failing- SNS is doing its best to stimulate the heart and keep it going- if you use a standard dose of beta blocker (IN ACUTE HEART FAILURE)-> blocks these effects and causes a drop is pressure which is bad
can kill people with acute heart failure
thus it is only used in chronic heart failure and in very small doses

Question 15

How does sacubitril and valsartan affect heart failure?

Answer 15

Combination therapy- known as entresto
sacubitril= neprilysin inhibitor- potentiate the effects of cardiac natriuretic peptides
valsartan= angiotensin 2 inhibitor- ARB

Question 16

What effect does digoxin have on heart failure patients?

Answer 16

Doesnt effect mortality- wont make you live longer

less likely to be hospitalised

Question 17

What is ivabradine? How does it effect heart failure?

Answer 17

Blocks the funny current (part of cardiac action potential) in the sinus node
thus it slows down heart rate by decreasing sinus node firing
used in angina and HF
has no benefit in terms of CVD
significant benefit in terms of death from heart failure
significant benefit in terms of hospitalization due to HF

Question 18

What is acute heart failure?

Answer 18

heart failure that occurs suddenly and often without warning, unlike chronic heart failure
could be due to a heart attack, or a ruptured valve etc

Question 19

What drugs need to be given to a person with serious pulmonary oedema?

Answer 19

oxygen
diamorphine- relaxing cerebral effects and is a vasodilator
nitrates- vasodilation
loop diuretics- work quickly, acute effect= vasodilation, followed by diuresis

Question 20

When and why would we give someone an inotrope?

Answer 20

When a person has acute heart failure due to a known cause- ruptured valve etc
tide the person over if they were going to die imminently (wouldn’t last for surgery)
2 types:
-adrenergic agonists- catecholamine type drugs
-PDE 3 inhibitors- PDE causes the breakdown of cAMP- block the breakdown- potentiate the effect of cAMP- stimulates the CNS

Question 21

Examples of adrenergic agonists

Answer 21

Inoconstrictors- 
noradrenaline, adrenaline and dopamine 
(ino- work on beta 1 receptors) (constrictors- work on beta alpha 1 receptors)
Inodilators-
dobutamine, dopexamine, isoproterenol
(dilators- work on beta 2 receptors)

Question 22

Why are PDE3 inhibitors only administered for a couple of days?

Answer 22

Long term use- associated with increased mortality

die more frequently on this drug if used long term

Question 23

What are the typical drugs a heart failure patient would be on

Answer 23

Beta-blocker- low dose gradually building uo
ACE inhibitors- low dose gradually building up
spironolactone- aldosterone antagonist
diuretic- furosemide etc
if patient still has symptoms- fast heart rate etc- administer ivabradine and digoxin