38. `Heart Failure Treatment (Pharmacology) Flashcards
1
Q
What is heart failure characterised by? (5)
A
- progressive cardiac dysfunction
- dyspnoea
- tiredness
- neurohormonal disturbances
- sudden death
2
Q
Define heart failure.
A
Heart failure is a state in which the heart is unable to pump blood at the rate commensurate with the requirements of the tissues or can do so only from high pressures. It’s a SYNDROME not a disease.
3
Q
What are 2 types of heart failure?
A
- systolic heart failure
1. diastolic (or relaxation) heart failure
4
Q
What is systolic heart failure?
A
Decreased pumping function of the heart which results in fluid back up in the lungs and heart failure
5
Q
What is diastolic (or relaxation) heart failure?
A
- Involves a thickened and stiff heart muscle and as a result the heart doesn’t fill with blood properly
- This results in fluid backup in the lungs and heart failure
6
Q
What is the prevalence of chronic heart failure and what is the prognosis like?
A
- prevalence is 2-10% of population
- poor prognosis, with 5 year mortality of 50% and rising to 80% in a year for some patients
7
Q
What does chronic heart failure incidence increase with?
A
Increases with age (and if you’re male)
8
Q
What are the main risk factors for heart failure? (11)
A
- coronary artery disease
- hypertension
- valvular heart disease
- alcoholism
- infection (viral)
- diabetes
- congenital heart defects
- Other: obesity, age, smoking, high or low haematocrit level (RBC), obstructive sleep apnoea
- dyslipidaemia (abnormal lipid amount)
- history of MI or angina
- l.ventricular hypertrophy
9
Q
What do all the cardiac risk factors lead to eventually? What is the pathological progression for chronic heart failure?
A
- All risk factors lead to myocardial injury which leads to neurohormonal stimulation and myocardial toxicity
- Pathologic remodelling and low ejection fraction leads to symptoms (e.g. fatigue, dyspnoea, oedema)
- Pump failure due to symptoms leads to chronic heart failure and sometimes sudden death
10
Q
State Frank-Starling Law.
A
If the muscle of a healthy heart is stretched, it will contract at a greater force and pump out more blood. (i.e. bigger preload means stronger contraction which means more stroke volume)
11
Q
What happens to Frank-Starling Law in systolic dysfunction?
A
- this relationship is lost in failing or damaged heart
12
Q
Describe what happens to the heart in systolic dysfunction in terms of:
- circulatory volume
- force of contraction
- cardiac output
- RAAS system
A
- as circulatory volume increases, the heart dilates but force of contraction weakens and cardiac output drops
- decrease in cardiac output activates RAAS system (renin angiotensin aldosterone system)
- ongoing cycle of RAAS is activated, circulatory volume increases and cardiac performance (pump) deteriorates
13
Q
What occurs to the heart over time, as RAAS continues to be dilated when pumping ability decreases?
A
- the heart starts to dilate as volume of blood increases but pumping weakens
- cardiac myocytes undergo hypertrophy and fibrosis
- heart is further weakened
14
Q
What causes diastolic dysfunction heart failure or preserved ejection fraction heart failure?
A
Sustained hypertension
15
Q
What causes systolic dysfunction heart failure?
A
myocardial damage i.e. MI
16
Q
What happens to the body when it detect a fall in cardiac output?
A
- body registers it as loss in circulatory volume
- vasoconstrictor system activation (sympathetic system)
- slat and water retaining system activation (RAAS)
17
Q
What is the main mechanism which tries to compensate during heart failure?
A
Renin angiotensin aldosterone system (RAAS)
18
Q
What does ACE do?
A
Converts angiotensin 1 into angiotensin 2 which induces aldosterone secretion
19
Q
What does aldosterone secretion do in terms of:
- salt and water retention
- plasma volume
- preload
- cardiac workload
A
- increases salt and water retention
- increases plasma volume
- increases preload
-increases cardiac workload
which all lead to heart failure
20
Q
What does peripheral venoconstriction as a result of angiotensin 2 do to:
- afterload
- cardiac output
A
- increases afterload
- decreases cardiac output
which all lead to heart failure
21
Q
What does the RAAS system cause the release of?
A
- angiotensin 2
- aldosterone
22
Q
What is the end results of RAAS? (3)
A
- salt and water retention
- vasoconstriction
- hypertrophy of fibrosis of cardiac myocytes
23
Q
Activation of sympathetic system causes the release of noradrenaline and adrenaline, which cause what? (3)
A
- vasoconstriction
- stimulate renin release
- myocyte hypertrophy
24
Q
What two chemicals cause salt and water excretion and vasodilation?
A
- natriuretic peptide system (ANP and BNP) atrial and brain
- EDRF: endothelium derived relaxing factor
25
What is the final result of chronic heart failure? (3)
- failing heart that can't pump out sufficient blood to supply needs of the body
- progressive retention of salt and water which results in oedema and pulmonary oedema
- progressive myocyte death and fibrosis
26
What does heart failure treatment aim to do? (3)
1. improve symptoms
2. improve survival
3. improve symptoms AND survival
27
What medication aims to improve heart failure symptoms? (2)
1. diuretics
| 2. digoxin
28
What medication aims to improve heart failure survival? (2)
1. beta blockers
| 2. Ivabradine
29
What medication aims to improve heart failure symptoms and survival? (3)
1. ACEIs and ARBs
2. spironolactone
3. Valsartan-sacubitril
30
What does symptomatic treatment aim to do? (3)
1. inhibit detrimental neurohormonal adaptations.
2. enhance beneficial neurohormonal adaptations
3. enhance cardiac function
31
What are the most common diuretics used for treatment of chronic heart failure symptoms? (2)
1. furosemide
2. bumetanide
(symptomatic treatment)
32
What beta blockers are commonly used to block sympathetic system activation/detrimental hormonal changes in chronic heart failure? (3)
1. carvedilol
2. bisoprolol
3. metoprolol
(blocking detrimental hormonal changes)
33
What 2 groups of drugs are available to block the effects of angiotensin II?
1. ACEIs: ramipril
| 2. Angiotensin antagonists: Valsartan and Losartan (ARBs)
34
What does spironolactone do which aims to improve symptoms and survival?
- blocks effects of aldosterone
35
What converts angiotensinogen to angiotensin 1?
renin
36
What converts angiotensin 1 into angiotensin 2?
ACE
37
When angiotensin 2 is converted by non-ACE pathways into aldosterone, what effects does this cause? (4)
1. sympathetic activation
2. vasoconstriction
3. cell growth
4. Na/H2O retention
38
What does natriuretic peptide system do? (ANP/BNP)
- enhances beneficial hormonal changes
- potent vasodilators and natriuretic agents
- metabolised by neutral endopeptidases
39
What is the effect of Neprolysin on ANP/BNP natriuretic peptides? (2)
- prevents metabolism
| - enhances ANP/BNP actions
40
What is a drug that is a positive inotrope?
Digoxin
41
What do positive inotropes do?
- improve ability of the heart to pump and so improve cardiac status
42
What are common vasodilators which reduce preload and afterload which improve cardiac function? (2)
- isosorbide mono or di nitrate
| - hydralazine (arterial dilator)
43
Does mortality for chronic heart failure remain high with therapy?
Yes, despite risk reduction therapies, mortality rates remain very high (risk reduction with ACEIs and beta blockers only reduce mortality by 35%)
44
Which cancers have a better prognosis that heart failure? (4)
1. bladder
2. uterus
3. prostate
4. breast
45
Describe the function of the most commonly used loop diuretic, furosemide.
- removes excess salt and water
- induce profound diuresis (urination)
- inhibit Na-K-Cl transporter in the loop of henle
- work at very low glomerular rates
- prevent reabsorption of 20% filtered na and water
46
What are common loop diuretics which work on the loop of Henle? (3)
1. furosemide
2. bumetanide
3. ethacrynic acid
47
What diuretics work on proximal tubule of nephron? (3)
1. triamterene
2. amiloride
3. spironolactone
48
What diuretics work on distal tubule of nephron? (3)
1. thaizides
2. metolazone
3. indapamide
49
What can be done for diuretic resistant patients?
diuretics can be given with thazide diuretics to improve outcome (powerful combo)
50
What are adverse drug reactions to diuretics? (5) HYPOs
1. dehydration
2. gout
3. hypokalaemia, hyponatraemia
4. impaired glucose tolerance, diabetes
5. hypotension
51
What does a drug interaction between furosemide and aminoglycoside produce?
aural and renal toxicity
52
What does drug interaction between furosemide and lithium, NSAIDs and vancomycin produce?
renal toxicity
53
What does a drug interaction between furosemide and antihypertensives produce?
profound hypotension
54
Overall, furosemide should NOT be mixed with which drugs to avoid dangerous drug-drug interactions? (5)
1. NSAIDs
2. lithium
3. vancomycin
4. aminoglycoside
5. antihypertensives
55
Therefore what drugs reduce mortality from chronic heart failure? (4)
1. angiotensin blockade
2. beta blockers
3. aldosterone blockade
4. ANP/BNP enhancement
56
What is an alternative enzyme in heart tissue which can convert angiotensin 1 to angiotensin 2 without ACE?
chymase (it cannot be blocked by ACEIs)
57
Damage to which body structures does angiotensin 2 cause organ damage to? (4)
1. brain
2. blood vessels
3. kidneys
4. heart
58
What organ damaging effect does angiotensin 2 have on the brain and blood vessels? (4)
1. atherosclerosis
2. vasoconstriction
3. vascular hypertrophy
4. endothelial dysfunction
59
What organ damaging effect does angiotensin 2 have on the heart? (4)
1. l. ventricular hypertrophy
2. fibrosis
3. remodelling
4. apoptosis
60
What organ damaging effect does angiotensin 2 have on the kidneys? (4)
1. decrease in glomerular filtration rate
2. increase in proteinuria
3. increase in aldosterone release
4. glomerular sclerosis
61
What are the most commonly used ACEIs? (3)
1. ramipril
2. enalapril
3. lisinopril
62
What effect do ACEIs have?
- competitively block ACE (angiotensin converting enzyme)
- prevent conversion of angiotensin 1 into angiotensin 2
- reduce preload and afterload on heart
63
What beneficial effect do ACEIs have on post MI patients and heart failure patients?
1. reduce mortality
2. reduce morbidity
3. reduce onset of heart failure (in post MI patients)
64
What are adverse drug reactions to ACEIs? (6)
1. first dose hypotension
2. cough
3. angioedema
4. renal impairment
5. renal failure
6. hyperkalaemia
65
What does a drug interaction of ACEI with NSAIDs cause?
acute renal failure
66
What does a drug interaction of AEI with pottasium supplements and potassium sparing diuretics cause?
hyperkalaemia
67
Overall, what drugs should NOT be used with ACEIs? (3)
1. NSAIDs
2. potassium supplements
3. potassium sparing diuretics
68
What do ARBs block?
block the angiotensin 2, AT1 receptor
69
When are ARBs give to patient?
- only when patient intolerant to ACEIs
| - they are not as effective as ACEIs
70
What are two angiotensin 2 receptors?
1. AT1
| 2. AT2
71
What does activation of AT1 receptor do? (5)
1. vasoconstriction
2. vascular proliferation
3. aldosterone secretion
4. cardiac myocyte proliferation
5. increased sympathetic tone
72
What does activation of AT2 receptor do? (3)
1. vasodilation
2. antiproliferation
3. apoptosis
73
Why is AT1 receptor blocked?
- more selective and specific blockade of angiotensin 1 at At1 receptor rather than non-specific blockade by ACEIs for example
74
What is Valsartan- Sacubitril (ARNI)?
- combined valsartan and ARB and neprilysin
- ARB blocks AT1 receptor
- Neprilysin stops breakdown of ANP and BNP by neutral endopeptidases
75
What type of drug is spironolactone?
- Aldosterone antagonist
- K sparing diuretic
- inhibits actions of aldosterone
76
On which part of the nephron does spironolactone act on?
distal tubule
77
What is spironolactone used in combination with?
with loop diuretics and ACEIs
78
What is spironolactone useful for treating?
resistant oedema
79
What are 3 most commonly used beta blockers?
1. Carvedilol
2. Bisoprolol
3. Metoprolol
80
When should beta blockers be used?
- only in STABLE patients and not during an acute presentation stage
- they block actions of sympathetic system and may cause severe deterioration of chronic heart failure
- specialist use only since can be hazardous
81
What is Ivabradine an inhibitor of?
- specific inhibitor of the I current in sinoatrial (SA) node
- no action on other channels in the heart or vascular system
82
Does Ivabradine modify myocardial contractility?
- it doesn't modify heart contractility or intracardiac conduction even in impaired systolic function
83
When is it recommended to give patients Ivabradine?
- stable chronic patients who are receiving stabdard therapy including beta blockers at max. tolerated dose
- patients in sinus rhythm with heart rate at 70bpm or greater at rest
84
What sort of drug is Digoxin?
positive inotrope
85
What is the mechanism of digoxin?
- increases availability of calcium in the myocyte
| - no effect on mortality
86
Why does digoxin have to be administered carefully?
has a narrow therapeutic index
87
What are adverse side effects of digoxin? (3)
1. arrhythmias
2. nausea
3. confusion
88
What anticoagulant can be used to treat chronic heart failure?
Warfarin
89
Why is Warfarin used in patients with heart failure?
- dilated ventricle gives rise to thrombus formation and thromb-embolic events
- Warfarin prevents these events from causing problems
90
What is the therapeutic regime for treating chronic heart failure? (9)
1. furosemide +/- thiazide
2. furosemide +pulsated metolazone
3. ACEI
4. ARB
5. ARNI; angiotensin receptor neprilysin inhibitor
6. beta blocker +/- Ivabradine
7. MRA spironolactone
8. digoxin
9. warfarin
91
What are symptomatic reliefs seen in heart failure patients after therapy administered? (3)
1. dyspnoea
2. tiredness
3. lethargy
92
What clinical relief is seen in heart failure patients after therapy administered? (3)
1. peripheral oedema
2. ascites
3. weight
93
What should be monitored in a heart failure patient? (3)
1. symptoms and clinical signs
2. weight
3. patient education
