Drugs for treatment of Heart Failure

Question 1

What are the 3 cardinal manifestations of heart failure?

Answer 1

Dyspnea (shortness of breath)
Fatigue
Fluid Retention

Question 2

In most conditions, heart failure is associated with decreased cardiac output. What are 4 examples where cardiac output is high, but metabolic demands are also high, resulting in heart failure?

Answer 2

Hyperthyroidism
Beri Beri
Anemia
Major AV shunts

Question 3

What are the 4 levels of heart failure?

Answer 3

• I – only at levels of exertion that would limit
normal individuals
• II – on ordinary exertion
• III – on less-than ordinary exertion
• IV – symptoms of heart failure at rest

Question 4

What is the major determinant of contraction force?

Answer 4

Sarcomere length during diastole

Question 5

What is the major determinant of sarcomere length?

Answer 5

End diastolic filling pressure (pre-load)

Question 6

What are preload and afterload relative to cardiac function?

Answer 6

Pre - Diastolic filling pressure

After - Arterial pressure (resistance heart pumps against)

Question 7

Cardiac myocyte depolarization results in _ (ion) influx into the cell. This influx causing a change in membrane potential, stimulating calcium influx through _ type calcium channels. This influx causes more calcium release from the sarcoplasmic reticulum via _ receptors

Answer 7

Sodium
L-type
Ryanodine receptors

Question 8

What happens to the Na/Ca exchanger during depolarization? How is calcium removed to the sarcoplasmic reticulum? How is the remaining calcium removed?

Answer 8

Briefly reverse, now calcium pumped into cell
SERCA, Calcium ATPase
Sarcolemmal Calcium ATPase

Question 9

What are 2 components of heart failure that may be present individually or in combination?

Answer 9

Systolic dysfunction: Weak contraction

Diastolic dysfunction: Incomplete relaxation (not enough filling)

Question 10

One of the earliest steps in heart failure is a reduction in cardiac output. What are 2 compensatory systems activated as a result of this reduction?

Answer 10

Sympathetic NS

Renin Angiotensin System

Question 11

What are the major forces that cause cardiac remodeling during heart failure?

Answer 11

Increased intravascular and ventricular volume, leading to increased diastolic and systolic wall stress

Question 12

What are 3 neurohumoral factors that act directly on the myocardium to promote unfavorable remodeling?

Answer 12

Sympathetic NS
Ang II
Aldosterone

Question 13

What happens to the baroreceptor reflex during heart failure? What is increased as a consequence (3)?

Answer 13

Reduced function (reads high pressures as normal)
Sympathetic NS, Renin-Ang system, vasopressin

Question 14

Cardiac hypertrophy occurs during heart failure. Why is a larger heart deleterious?

Answer 14

A bigger heart operates at a reduced ionotropic state

Question 15

How is the renin angiotensin system altered during heart failure? Why?

Answer 15

Increased renin release

Increased symp. NS shunts blood from glomeruli, stimulating renin release

Question 16

What are 3 systems at work to sustain arterial pressure, despite decreased cardiac output during heart failure?

Answer 16

Symp NS
Renin Ang System
Vasopressin

Question 17

What is the effect of increased venous pressure during heart failure?

Answer 17

Reduced capillary return, edema

Question 18

What is the difference between stage A/B and stage C/D of heart failure?

Answer 18

Stage A/B - At risk for heart failure

Stage C/D - Have heart failure

Question 19

How are stage A and stage B heart failures different? How do their treatments differ?

Answer 19

A - Risk, no symptoms (ACE inhib., Ang receptor Blockers)

B - Structural disease, no symptoms (ACE inhib., Ang receptor Blockers, beta blockers)

Question 20

What is stage C heart failure? How is it treated?

Answer 20

Structural disease with current / prior symptoms

Diuretics, ACE inhibs, beta blockers

Question 21

What is stage D heart failure? How is it treated?

Answer 21

Refractory heart failure

Requires extraordinary measures (transplant, mechanical support, etc)

Question 22

What are 3 drug classes that can be used to reduce afterload?

Answer 22

ACE inhib.
Ang Receptor blockers
Isosorbide dinitrate / hydralazine

Question 23

For diuresis during HF, what 2 types of diuretics are used?

Answer 23

Loop diruretics

Spironolactone

Question 24

For positive ionotropy, what 3 types of drugs are used?

Answer 24

Adrenergic agonists
cAMP phosphodiesterase inhibitors
Digitalis glycosides

Question 25

What are 3 drug classes that are known to reduce mortality when used alone?

Answer 25

* ACEI * ARB * beta-blockers

Question 26

What are the 2 major peptides upregulated by ACE inhibitors?

Answer 26

``` Ang I (Ang 1-7, opposes classical RAS actions) Bradykinin (potent vasodilator) ```

Question 27

What property of ace inhibitors allow them to reduce afterload, Increase stroke volume and cardiac output?

Answer 27

More potent dialators or arterial vessels vs. venous vessels

Question 28

Captopril, enalapril, ramipril, lisinopril, quinapril | and fosinipril are all examples of _

Answer 28

ACE inhibitors

Question 29

What is the first line treatment for heart failure / reduced LVEF? What is this usually administered with?

Answer 29

ACE inhibitors | Beta blockers

Question 30

Angiotensin receptors mainly block what receptor subtype? What subtype is largely unaffected and what is its effect? What peptide is directly increased by this class of drug?

Answer 30

AT1 AT2 - promotes vasodilation and naturesis Increases Ang II

Question 31

What are 3 angiotensin receptor blockers used in the treatment of heart failure?

Answer 31

Losartan Valsartan Candesartan

Question 32

Which has better survival in heart failure patients, ACE inhibitors or Angiotensin receptor blockers? What happen to survival when both are combined?

Answer 32

Comparable survival rates for both | No additive benefit when both are combined

Question 33

What is the preferred class of diuretics for treatment of heart failure? What class may be used in patients with hypertension?

Answer 33

Loop diuretics | THiazides in hypertensive patients

Question 34

What class of drug will provide the fastest relief of symptoms in patients with heart failure?

Answer 34

Diuretics

Question 35

How should diuretics be used in treatment of stage C heart failure?

Answer 35

Should be used in combination with another agent, shouldn't be used alone

Question 36

How do diuretics affect survival in heart failure patients?

Answer 36

No mortality benefit, address symptoms

Question 37

How are sympatomimetics used in the treatment of heart failure? Why?

Answer 37

Used only for short term | Increase mortality in patients

Question 38

What are 3 benefits of beta blockers in heart failure patients?

Answer 38

improve symptoms improve exercise tolerance increase LVEF

Question 39

What is the effect of phosphorylation of the ryanodine receptor? What drug class is blocks / reduces this phosphorylation?

Answer 39

Increased phospho. causes calcium leak from sarcoplasmic reticulum, decreased contractility Beta blockers

Question 40

What is the effect of beta blockers on cardiac remodeling?

Answer 40

Blocks remodeling

Question 41

What types of heart failure patients should get beta blockers? What is the exception?

Answer 41

All patients with HF due to LVEF | No beta blockers if contraindicated (reactive airway disease, bradycardia)

Question 42

What are 3 beta blockers used in heart disease and what are their receptor targets?

Answer 42

Bisoprolol Metoprolol - selective beta 1 block Carvedilol - blocks alpha 1, beta 1 and 2

Question 43

What is the effect of Metoprolol, carvedilol and bisoprolol on mortality?

Answer 43

All three reduce mortality

Question 44

What are the 3 cardiac glycosides used in the treatment of heart failure?

Answer 44

Digoxin Digitoxin Ouabain

Question 45

In addition of heart failure, what is another use for digoxin?

Answer 45

Arrythmias

Question 46

What is the mechanism of action of digoxin? What is its receptor target? What are 2 by products of improved contractility following digoxin treatment?

Answer 46

Increases contraction force by increasing intracell. calcium. Sodium/ potassium ATPase Reduced symp. NS activity, increased renal perfusion

Question 47

How does digoxin reduce the sodium gradient within the cell? What is the main channel affected? How does this affect calcium In the cell?

Answer 47

Reduces the gradient Blocks activity of the sodium calcium exchanger Increased calcium in cell, increase calcium uptake into sarcoplasmic reticulum, increase calcium release with depolarization, increased contractile force

Question 48

What is the effect of digoxin on cardiac baroreceptors? Why is this significant?

Answer 48

It resensitizes these receptors | It leads to decreased sympathetic and increased parasymp input to heart

Question 49

What is the receptor target of digoxin in the kidney? What is the significance?

Answer 49

It inhibits the sodium/potasium ATPase | Reduces sodium reabsorption in proximal tubule, leading to increase sodium in distal tubule, decreased renin release

Question 50

What are the glycosides approved for use clinically?

Answer 50

Only digoxin

Question 51

Digoxin is no longer a first line treatment for heart failure. What patients may be prescribed digoxin? (2)

Answer 51

Heart failure with atrial fibrillation | Patients refrctory to diuretcis, ACE inhib, ang inhib and beta blockers

Question 52

What is the major toxicity associated with digoxin? What use of digoxin predisposes a patient to toxicity? How can toxicity be countered?

Answer 52

Arrhythmias, cardiac block Long term use Digoxin immunotherapy

Question 53

What is the effect of digoxin on survival? What are risk associated with higher doses of digoxin?

Answer 53

No effect on survival | Increased risk of death from MI and arrhythmias

Question 54

What are the 2 examples of aldosterone antagonists provided? What 2 classes of drug must be prescribed with the?

Answer 54

Spironolactone and Eplerenone | 1) ACE inhib or ang receptor blocker and 2) diuretic

Question 55

What is the effect of aldosterone on the heart?

Answer 55

Negative cardiac remodeling effects

Question 56

What would be the effects of venodilators on heart function? (2)

Answer 56

Decrease filling pressure | Decrease intracardiac pressure

Question 57

Arteriodilator [increase/decrease] vascular resistance and [increase/decrease] renal perfusion which [promotes / prevents] diuresis

Answer 57

Decrease Increase Promotes

Question 58

Nitroglycerin, isosorbide dinitrate and isosorbide mononitrate. Among the preceding, which is Short acting? quick acting? Long acting?

Answer 58

Short acting - iso dinitrate Quick - Nitroglycerin Long - Iso mono-nitrate

Question 59

Isosorbide dinitrate preferentially works on [arteries / veins]. Its major action is to therefore decrease [preload / afterload]. It is usually used in concert with _

Answer 59

Veins Preload Hydralazine

Question 60

Hydralazine preferentially works on [arteries / veins]. Its major effect is to increase perfusion of _ [organ]. What is the drug that is a combo of isosorbide dinitrate and hydralazine?

Answer 60

Arteries Kidneys BiDil

Question 61

What is the major drug for use during decompensated heart failure? What are the 2 heart function related parameters it reduces?

Answer 61

IV Sodium Nitroprusside | Ventricular filling pressure, systemic vascular resistance

Question 62

To treat acute MI or quickly reduce ventricular filling pressure, what is the drug of choice? What type of vessel is it selective for?

Answer 62

IV notroglycerin | Venous capacitance vessels

Question 63

What are 3 parenteral positive ionotropic agents that can be used to treat refractory heart failure patients?

Answer 63

Dobutamine Dopamine Milrinone

Question 64

With regards to the heart and vasculature, what are the target receptors and effects of dopamine?

Answer 64

Beta adrenergic receptors (stimulation) - increased contractility Alpha adrenergic receptors (stimulation) - increases vascular pressure (good if patient has low BP)

Question 65

What is the receptor target for dobutamine? It is the drug of choice for what cardiac disorders?

Answer 65

Beta agonist | Systolic dysfunction and congestion

Question 66

What is the major effect of dobutamine, positive ionotropy or chronotropy? What are the 2 major side effects?

Answer 66

Positive ionotropy | Tachycardia and arrhythmias

Question 67

What are 2 cAMP phosphodiesterase inhibitors that can be used to treat advanced heart failure? What is the main ion affected? Where is this ion affected?

Answer 67

Inamrinone and Milrinone Calcium Increased cytoplasmic calcium

Question 68

Between Inamrinone and Milrinone , which has more favorable side effect profile, shorter half live, and more selective for PDE3?

Answer 68

Milrinone