3.1 HF Pharmacology 1

Question 1

• What is the definition of HF?
• What are the two types and what is the mechanistic problems?
• What are the symptoms of both?

Answer 1

• HFis the inability to pump sufficient blood. It is hte end-stage of various cardiac/circulatory diseases.
• Two types:
  
  • ​Systolic failure (HFrEF) is an inability to pump blood (reduced EF)
  • Diastolic failure (HFpEF) is an inability of the heart to relax and fill with blood (preserved EF)
• Symptoms are related to collection of interstitial fluid– dyspnea, fatigue, and fluid retention

Question 2

Explain systolic vs. dystolic dysfunction.

Answer 2

• Systolic dysfunction is due to over-dilation over the ventricles. It is defined as an EF of < 40-50% though it can go as low as 10-20%
• Diastolic failure results from hypertrophe and stiffness in the ventricles. The EF remains high but output is limited.
• The two can co-exist, if hypertrophed ventricles dilate over time.

Question 3

What are the symptoms of left sided VS right sided HF?

Answer 3

L side failure = inability to pump blood coming from the lungs into systemic circulation

R side failure = inability to pump de-oxygenated blood out of the vena cava and into the lungs

Note on isolated right side failure:

• R HF may be secondary to chronic pulmonary problems
• Distended veins
• Ascites and fluid weight gain

Question 4

What are three ways the body compensates for heart failure?

Answer 4

1. Increased SNS activity
2. Activation of Renin-Angiotensin-Aldosterone system
3. Myocardial hypertrophy

Question 5

Review the mechanisms of Left Sided systolic HF

Question 6

What can we do to affect RAS in treating L sided systolic HF?

Answer 6

ACE-I’s, ARBs, or aldosterone antagonists

Question 7

What drugs can we use to target vasoconstriction in treating L sided systolic HF?

Answer 7

Vasodilator,s Thiazide diuretics, Beta blockers

Question 8

How do we target RAS in treating L sided HF?

Answer 8

ACE-I’s, ARBs, and aldosterone antagonists

Question 9

How can we directly target cardiac output (CO) in treating L sided systolic HF?

Answer 9

Inotropes

Question 10

What are target systems (and goals) for treating L sided HF and what are the associated drugs?

(excluding natriuretic peptide system)

Answer 10

Question 11

What is the purpose of the natriuretic peptide system?

How does it work?

How can we artificially promote it?

Answer 11

The NPS is “nature’s diuretic” and “nature’s vasodilator.” It counterbalances the RAS.

1. When circulating volume is too great, the heart becomes stretched and ANP and BNP are released to counter.
2. In the kidney ANP/BNP increase the wasting of sodium (followed by water). Aldosterone secretion decreases.
3. ANP/BNP increase vasodilation and reduce endothelial permeability.
4. Angiotensin II directly activates release of ANP/BNP to counter itself.

The amounts of NPS can be promoted by the inhibition of neprilysin, the enzyme that breaks down ANP/BNP. NPS effects can also be potentiated with Sacubitril/Valsartan + an ARB.