Pharmacological Management of Heart Failure

Question 1

Compensatory Hypertrophy vs Cardiac Failure

Answer 1

Compensatory Hypertrophy keeps an increased LV diastolic volume with no increased wall stress. Cardiac failure has a greatly increased LV diastolic volume (increased radius) and increased wall stress for both systole and diastole.

Question 2

Most Prevalent Primary cause of HF

Answer 2

Coronary Artery Disease (CAD) 60% of cases.

Question 3

New York Heart Association Classifications of Cardiac Function Status

Answer 3

• Class I No limitations, no symptoms with ordinary activities
•   Class II Slight limitations; symptoms with ordinary activities
•   Class III marked limitations: symptoms with < ordinary activities
•   Class IV Symptoms of cardiac insufficiency at rest

Question 4

(T or F) Heart Failure has an increased amount of Parasympathetic Stimulation.

Answer 4

False. Increased Sympathetic stimulation. Leads to pathological remodeling.

Question 5

ACE Inhibitors and ARBs Target?

Answer 5

Heart, Kidneys and Blood Vessels

Question 6

Vasodilators

Answer 6

•  Perhaps the most important category of
drugs used in the treatment of heart failure
•  Nitrates
•  ACE-inhibitors
•  ARB’s (angiotensin receptor blockers)

Question 7

RAAS Definition

Answer 7

Renin-Angiotensin-Aldosterone System. Angiotensinogen -> Angiotensin II which causes the production of aldosterone from the zona glomerulosa in the adrenal cortex.

Question 8

Ang II stimulation pathway

Answer 8

Angiotensin II binds the AT-1 receptor. Activation causes stimulation of MAPK and ERK 1/2. This leads to stimulation of TGF-Beta, AP-1 , collagen 1 and fibronectin. Also causes changes in the actin filament dynamics. This leads to vasoconstriction, hypertrophy, fibrosis and apoptosis. END RESULT OF GROWTH AND REMODELING!

Question 9

Main Ang II Functions

Answer 9

Vasoconstriction, Activate SNS, Elevate aldosterone

Question 10

Differences between ACE-I’s?

Answer 10

Half-Life and Potency

Question 11

Pro-drug ACE-I

Answer 11

Enalapril (oral) to enalaprilat (IV only). (cleaves ethyl group)

Question 12

Combinational Therapy Vasodilator Treatment? Population?

Answer 12

BiDil- Isosorbide dinitrate (ISDN) and hydralazine (HDZ). Used in african american population.

Question 13

1st Gen Beta-Blocker

Answer 13

Nonselective! (block Beta 1 and 2 receptors)

Propanolol

Question 14

Dominant Beta receptor of the heart? of the vasculature and pulmonary system?

Answer 14

Heart- B1

Vasculature and pulmonary- B2

Question 15

2nd Gen Beta-Blocker

Answer 15

Selective blockade of β1- or β2-AR

Metoprolol, atenolol, betaxolol (all β1-AR selective)

Question 16

3rd Gen Beta-Blocker

Answer 16

Selective or nonselective β-blockade plus ancillary property which produces a favorable pharmacological effect
Carvedilol (α-AR blockade, anti-oxidant properties, guanine-nucleotide modulatable binding, “tight” receptor binding)

Question 17

Two Beta Blockers for Treating Heart Failure

Answer 17

Metoprolol (Toprol-XL) and Carvedilol (Coreg). Both have extended release, QD tablets

Question 18

Length of time before B-Blockers begin to work?

Answer 18

On average, 3 to 6 months but can be as long as 6 to 9 months. Also, a portion of patients never are able to reach sufficient doses during titration.