CPR 8.05 Pharmacology of Heart Failure

Question 1

What are the general goals of treating heart failure?

Answer 1

Reduce Sx and slow progression. Manage acute episodes

Question 2

In what 2 general ways can we aim to treat heart failure?

Answer 2

1. Improve CO: increase reserve capacity, decrease preload and afterload, slow down remodeling.
2. Improve secondary symptoms: decrease edema and imprve breathing.

Question 3

Describe 3 factors that contribute to cardiac remodeling

Answer 3

1. Increased beta-1 recpetor activation
2. Increased ANG receptor activation
3. Increased aldosterone activity

Question 4

Which drug classes have been shown to help prevent remodeling and reduce mortality?

Answer 4

ACE-I’s, ARB’s, Beta blockers (Beta 1 selective ones such as metorpolol, bisoprolol, Nebivolol, Carvedilol which is also alpha 1 antagonist), and mineralcorticoid recpetor antagonists (Spironolactone and Eplerenone),

Question 5

What is the most common example of a loop diuretic used in the treatment of HF?

Answer 5

Furosemide

Question 6

What is the MOA, Indications, and Toxicities of Furosemide in its treatment of HF?

Answer 6

(1) MOA: Increased excretion of salt and water reduces preload, afterload, and pulmonary/peripheral edema.
(2) Indications: First line agent. Used in acute and chronic heart failure.
(3) Toxicity: Hypovolemia, Hypokalemia, Orthostatic hypotension.

Question 7

What is an alternative diuretic that could potentially be used in treating HF, albeit less efficacious?

Answer 7

Thiazide

Question 8

What two aldosterone antagonists are commonly used to treat HF?

Answer 8

Spironlactone and Eplerenone

Question 9

What is the MOA and Indications for Spironlactone and Eplerenone?

Answer 9

(1) MOA: Block aldosterone recpetors and thus increase salt and water excretion (though not to same extent as thiazides or loop diuretic).
(2) Indications: Reduce remodeling and mortalitiy. Used in combo with diuretics, ACE-I’s and ARB’s.

Question 10

What are some examples of ACE-I’s?

Answer 10

Benzapril, Captopril, Enalapril

Question 11

What are some examples of ARB’s?

Answer 11

Losartan, Valsartan,

Question 12

What oars the MOA and Indications for ACE-I’s and ARB’s?

Answer 12

1. MOA: Increase arterial and venous dilation, thus reduce preload and afterload. Reduce aldosterone secretion thereby decreasing salt and water retention. Reduce cardiac remodeling. Considered first line agents along with diuretics.
2. Indications: chronic heart failure; first line for left ventricular dysfunction with no edema (ACE-I without diuretic would be best choice here)

Question 13

What are some beta blockers used in HF?

Answer 13

Metoprolol, Bisoprolol, Nebivolol, Carvedilol

Question 14

What is the MOA for Beta blockers?

Answer 14

Block effects of high [NE] and thus block sympathetic activation. Up-regulate beta-receptors to increase cardiac reserve. Decrease HR. Reduce remodeling.

Question 15

Isorbide Dinitrate, Hydralazine, Bidil, and Sodium nitruprusside are in what class of HF drugs?

Answer 15

Vasodilators

Question 16

What are the MOA and indications for Isorbide denigrate?

Answer 16

(a) MOA: Venodilaor. Reduces preload and ventricular stretch.
(b) Indications: Acute and chronic heart failure.

Question 17

What are the MOA and indications for hydrazine?

Answer 17

(a) MOA: Arteriolar dilator. Decreases SVR.

(b) Indications: Acute decompensated heart failure.

Question 18

What are the MOA and indications for Bidil? (Isorbide Dinitrate/Hydralazine)

Answer 18

(a) MOA: Combine venial and arterial dilation.

(b) Indications: African Americans. Reduces mortality.

Question 19

What are the MOA and evidence on mortality for Sodium Nitroprusside?

Answer 19

(a) MOA: Combined venous and arterial dilation. Reduces preload and afterload.
(b) Mortality? Improved survival NOT documented.

Question 20

What is the cardiac glycoside frequently used in the treatment of HF?

Answer 20

Digoxin

Question 21

What is the MOA and Indication for Digoxin?

Answer 21

(a) MOA: Na+/K+ ATPase inhibition causes the Na+-Ca++ exchanger to be inhibitired in cardiac myocytes which leads to reduced Ca++ efflux. Increased Ca+ in SR procues moderate increased inotrpy.
(b) Indications: Used when diuretics and ACE-I’s fail to control sx.

Question 22

Describe the effectiveness and side effects of Digoxin

Answer 22

(c) Effectiveness: works in 50% of patients with systolic dysfunctions. Reduces hospitalizations, but doesn’t improve mortality and increases likelihood of sudden death (pro-arrhytmic)
(d) Side Effects: naussea, vomiting, diarrhea, cardiac arrhythmias. Increased likelihood of sudden death.

Question 23

Dobutamine is in what class of HF drugs?

Answer 23

Beta receptor agonist

Question 24

What are the MOA and indications for Dobutamine?

Answer 24

2. MOA: beta-1 slective agonist. Increases cardiac contractility and CO.
3. Indications: Acute decompensated heart failure, Cardiogenic shock, Intermittent therapy in chronic therapy to reduce Sx.

Question 25

Describe the side effects and pharmacokinetics of Dobutamine

Answer 25

3. Side effects: can induce tachyphylaxis beta-adrenergic receptors. Arrhythmias.
4. Pharmacokinetics: very short half lives, IV only.

Question 26

Dopamine is what type of HF drug?

Answer 26

It is a D-1 Receptor agonist (also kind of a beta agonist)

Question 27

What are the MOA and indications for Dopamine?

Answer 27

2. MOA: activates dopamine D1 receptors in kidney and increases renal blood flow. At higher concetnrations; activates beta and alpha-adrenergic receptors and increases CO and BP. (Dopamine is a precursor for NE)
3. Indications: Heart failure complicated by severe hypotension. Acute decompensated HF. Cardiogenic shock.

Question 28

Describe the toxicities and pharmacokinetics of Dopamine

Answer 28

4. Toxicities: arrhythmias.

5. Pharmacokinetics: very short half lives, IV only.

Question 29

What class of drug is Milrinone

Answer 29

Bipyridine

Question 30

Describe the MOA and indications for Milrinone

Answer 30

1. MOA: Pde3 inhibitor causes increased IC cAMP in heart and vascular smooth muscle. Results in increased vasodilation, lowered PVD, and increased cardiac contractility.
2. Indications: Used in acute decompensated heart failure.

Question 31

Describe the pharmacokinetics and Side effects of Milrinone

Answer 31

2. Pharmacokinetics: administered IV despite good oral bioavailability.
3. Side effects: arrhytmias, increased mortality with chronic use.