Congestive Heart Failure (Exam III)

Question 1

What’s the 5 year mortality rate for heart failure?

Answer 1

50%

Question 2

What is the most common cause of heart failure?
What is the progression of this disease process?

Answer 2

Coronary Artery Disease

CAD → Angina → MI → Scarring/Remodeling → HF

Question 3

Differentiate systolic HF vs diastolic HF.

Answer 3

Systolic HF = reduced cardiac function (i.e. pumping)
Diastolic HF = reduced diastolic filling (usually hypertrophy)

Question 4

What happens to Ejection Fraction (EF) in systolic vs diastolic failure?

Answer 4

Systolic HF: ↓ EF ↓ CO
Diastolic HF: ↓ CO, normal EF.

Question 5

What is the rarest form of heart failure?

What 4 examples were given that can cause this heart failure?

Answer 5

“High-Output” Failure = normal CO, insufficient for bodily demands.

1. Hyperthyroidism
2. Beriberi disease
3. Anemia
4. Arteriovenous shunts.

Question 6

How is End-Diastolic Volume (EDV) calculated?

Answer 6

Passive Filling + Atrial Contraction + End-Systolic Volume (ESV) = EDV

Ex. 65ml + 25ml + 50ml = 140ml EDV

Question 7

How is stroke volume calculated?

Answer 7

EDV - ESV = SV

140ml - 60ml = 80ml

Question 8

What 3 examples were given in lecture for decreasing preload?

Answer 8

1. Na⁺ restriction
2. Diuretics
3. Venodilation (nitroglycerin, etc.)

Question 9

Describe the pathologic positive feedback mechanism of heart failure associated with excessive afterload.

Answer 9

↓ CO = ↑ NE/Epi → ↑ afterload = ↓ CO

rinse and repeat

Question 10

Which compensatory mechanism is the first to respond in a situation of decreased cardiac output (CO) ?

Answer 10

↑ Heart Rate

Question 11

Which 3 mechanisms influence stroke volume?

Which of these 3 negatively affects CO?

Answer 11

Preload, contractility, and afterload.

↑ afterload = ↓ CO

Question 12

Which pump is going to influx Ca⁺⁺ into the sarcoplasmic reticulum for storage?

Answer 12

SERCA (Sarcoplasmic Reticulum Ca⁺⁺ ATPase Pump)

Question 13

What molecule binds to and holds Ca⁺⁺ in the sarcoplasmic reticulum?

Answer 13

CalS (Ca⁺⁺ Sequestrin)

Question 14

In broad strokes, what is the process for Ca⁺⁺ to affect myocardial contractility?

Answer 14

1. “Trigger” Ca⁺⁺ enters cell via action potential.
2. Ca⁺⁺ binds to SR, releasing Ca⁺⁺ stores.
3. Ca⁺⁺ binds w/ myosin = contraction

Question 15

What 3 factors effect the amount of “trigger” Ca⁺⁺ that enters a sarcomere/myocardial cell?

Answer 15

1. Amount of L-Type Ca⁺⁺ channels
2. Duration of channel opening
3. SNS stimulation.

Question 16

How do β1 agonists affect trigger Ca⁺⁺ levels?

Answer 16

β-1 agonists ↑ time that Ca⁺⁺ L-channels are open = ↑ trigger Ca⁺ to enter the cell.

Question 17

What drug has been stipulated as being both pro-arrythmic and anti-arrythmic?

Answer 17

Digoxin

Question 18

What is the mechanism of action of digoxin?

Answer 18

1. Digoxin binds to and inhibits Na⁺K⁺ATPase Pump.
2. ↓ intracellular K⁺ = ↑ intracellular Na⁺
3. Na⁺/Ca⁺⁺ antiporter is reversed.
4. ↑ intracellular Ca⁺⁺

Question 19

Which drug is a cardiac glycoside?
What is this drug used for?
What is it derived from?
What is its therapeutic index

Answer 19

• Digoxin
• Only + oral inotrope
• Foxglove plant
• Narrow TI = 2

Question 20

What is the bioavailability of digoxin?
What is the T½ of digoxin?
What is the excretion of digoxin?

Answer 20

• 65-80%
• T_1/2= 36-40 hours
• 2/3 excreted unchanged by kidneys

Question 21

What are the electrical effects of digoxin?
What does toxic dosing of digoxin cause?
What is the “digitalis effect” on an EKG?

Answer 21

• ↑ PR interval, ↓ QT interval
• Tachycardia, fibrillation, cardiac arrest
• Downward “swoop” on ST segment

Question 22

How does hyperkalemia affect digoxin?

How does this compare with hypercalcemia and hypomagnesemia?

Answer 22

↑ K⁺ competes with digoxin and decreases effect.

↑ Ca⁺⁺ and ↓ Mg⁺⁺ = arrhythmias

Question 23

What does phosphodiesterase-3 inactivate?

Knowing this, what would a PDE-3 inhibitor do to these?

Answer 23

cAMP and cGMP

PDE-3 Inhibition = ↑ cAMP & ↑ cGMP

Question 24

Which PDE-3 Inhibitor is a bipyridine?

How does this drug produce myocardial contraction and smooth muscle relaxation?

Answer 24

Milrinone

PDE-3 Inhibition:
1. ↑ cAMP = myocyte contraction
2. ↑ cGMP = smooth muscle relaxation

Question 25

What should be known about the pharmacokinetics of milrinone (i.e. route of administration, T½, and site of excretion) ?

Answer 25

* Parenteral (IV) only * T½ = 2-3 hours * Urinary excretion

Question 26

Why might a phosphodiesterase inhibitor be preferred over digoxin?

Answer 26

No inhibition of the Na⁺ K⁺ ATPase pump.

Question 27

Which β agent is the most utilized drug for acute HF?

Answer 27

Dobutamine

Question 28

Which drug class reduces preload, edema, and cardiac size? How does this class accomplish this? Is the process of reduction of cardiac size a rapid one?

Answer 28

* Diuretics * Reduction of salt and H₂O retention * Cardiac remodeling is a very gradual process.

Question 29

Which two drugs might be good choices to reduce compensatory responses to decreased cardiac output (i.e. HF)?

Answer 29

ACE Inhibitors (Captopril) & ARBs (Losartan)

Question 30

How do all vasodilators, to one degree or another, treat heart failure?

Answer 30

Reduction of preload & afterload

Question 31

How do nitroprusside, hydralazine, and nitrates produce vasodilation?

Answer 31

Release of NO from drug or endothelium

Question 32

How do verapamil, diltiazem, and nicardipine produce vasodilation?

Answer 32

Ca⁺⁺ influx reduction

Question 33

How do minoxidil and diazoxide produce vasodilation?

Answer 33

↑ pK⁺ to hyperpolarize smooth muscle membrane.

Question 34

How does Fenoldepam produce vasodilation?

Answer 34

Activation of dopamine receptors

Question 35

How do β-blockers treat HF? Which β-blockers are preferred for HF? Should β-blockers be used in severe HF?

Answer 35

* Reduction of CO = less O₂ demand * β-1 selective and/or vasodilatory (nebivolol) * No

Question 36

How do Ca⁺⁺ Sensitizers work?

Answer 36

↑ inotropy + vasodilate * Stabilize Ca⁺⁺ bound conformation * Open K⁺ channels (hyperpolarize cell)

Question 37

Which drugs should be avoided in HF? What is the exception?

Answer 37

* NSAIDs (**except aspirin**) * Thiazolidinediones (Rosiglitazone & Pioglitazone) * Metformin (causes lactic acidosis) * Non-selective β-blockers for severe HF

Question 38

What are the stages of heart failure?

Answer 38

* Stage A - High risk, no symptoms * Stage B - Structural disease, no symptoms * Stage C - Structural disease, symptoms * Stage D - Refractory symptoms

Question 39

What is the best treatment for Stage A heart failure?

Answer 39

Risk-factor reduction and education

Question 40

If someone were to be treated for acute heart failure and be hyponatremic, would you use diuretics?

Answer 40

* No, could lower Na⁺ too much. * Conivaptan (ADH inhibitor) instead.