9. Positive Inotropic Agents

Question 1

When might acute HF occur?

Answer 1

after MI

Question 2

Acute HF or chronic HF: peripheral edema

Answer 2

chronic

Question 3

Acute HF or chronic HF: weight gain

Answer 3

chronic

Question 4

Acute HF or chronic HF: cardiomegaly

Answer 4

chronic

Question 5

Acute HF or chronic HF: most severe symptoms

Answer 5

acute

Question 6

What are the positive inotropic agents?

Answer 6

• Digoxin
• Dopamine
• Dobutamine
• Phosphodiesterase inhibitors

Question 7

What is the MOA of digoxin?

Answer 7

inhibits Na/K ATPase which increases the availability of intracellular Ca

Question 8

What are the therapeutic effects of digoxin?

Answer 8

positive inotropic effect due to increased availability of cytostolic Ca during systole

Question 9

Therapeutic doses of digoxin do not increase HR. (T/F)

Answer 9

True

Question 10

Without HF, _________ signals dominate.

Answer 10

parasympathetic

Question 11

With HF, ________ signals dominate.

Answer 11

sympathetic

Question 12

Therapeutic doses of digoxin __ (↑/↓) SNS activity.

Answer 12

decrease ↓

Question 13

Therapeutic doses of digoxin __ (↑/↓) PNS activity.

Answer 13

increase ↑

Question 14

Digoxin decreases SNS activity by regulating what?

Answer 14

baroreceptor sensitivity

Question 15

How does digoxin increase PNS activity?

Answer 15

• direct stimulation of vagal nuclei in brain

- decreasing conduction velocity of the heart and prolongs refractory period of pacemaker cells

Question 16

Excessive doses of digoxin produce toxicity by altering _________ ____.

Answer 16

peripheral NS

Question 17

What are the toxic effects of excessive digoxin on the peripheral nervous system?

Answer 17

• ↑ SNS activity

- ↑ PNS activity: bradycardia and heart block

Question 18

How do excessive doses of digoxin affect the heart?

Answer 18

Arrhythmias: high intracellular Ca in pacemaker cells leads to ventricular tachycardia or fibrillation

Question 19

What is the antidote to digoxin?

Answer 19

digoxin immune therapy: Digibind

Question 20

Dopamine is the endogenous precursor to what?

Answer 20

norepinephrine

Question 21

Low doses of dopamine stimulate primarily ___ and ___ receptors.

Answer 21

D1 and D2

Question 22

What is the physiologic response to low doses of dopamine?

Answer 22

dilation of renal vessels: ↑ GFR = diuresis

Question 23

Positive inotropic effects of dopamine occur at doses of ________.

Answer 23

higher doses: 3-10 mcg/kg/min

Question 24

The positive inotropic effects of dopamine are mediated by what?

Answer 24

β1 receptors in the heart

Question 25

What occurs at doses of dopamine > 10 mcg/kg/min?

Answer 25

- increased TPR | - excessive increase in HR

Question 26

What adrenergic receptors does dobutamine stimulate?

Answer 26

β1, β2, α

Question 27

In the heart, the primary effect of dobutamine is due to stimulation of what receptor?

Answer 27

β1

Question 28

At lower doses of dobutamine, there is a minimal increase in HR. (T/F)

Answer 28

True

Question 29

In the vasculature, α agonism due to dobutamine is significant and causes ADRs. (T/F)

Answer 29

False: a weak α agonist effect is negated by vasodilation from β2 activation

Question 30

Dobutamine does not activate dopaminergic receptors at any dose. (T/F)

Answer 30

True

Question 31

What is the MOA of phosphodiesterase inhibitors?

Answer 31

inhibits phosphodiesterase type III: intracellular enzyme that breaks down cAMP

Question 32

Increased cAMP levels increase intracellular Ca. (T/F)

Answer 32

True

Question 33

What is the effect of increased cAMP on smooth muscle cells?

Answer 33

vasodilation

Question 34

Phosphodiesterase inhibitors are much more potent inotropes than adrenergic agents. (T/F)

Answer 34

False: weaker inotrope

Question 35

What are the inotropic phosphodiesterase inhibitor agents?

Answer 35

Milrinone

Question 36

What is the route of administration of milrinone?

Answer 36

IV

Question 37

What is the primary ADR of phosphodiesterase inhibitors?

Answer 37

arrhythmias

Question 38

What is the agent currently under investigation to be used as positive inotrope in HF?

Answer 38

Levosimendan

Question 39

What is the MOA of levosimendan?

Answer 39

sensitizes troponin-C in myofilaments to intracelular Ca

Question 40

How does levosimendan alter intracellular Ca levels?

Answer 40

it does not

Question 41

Acute or chronic HF? | Presents as anatomical abnormalities that develop gradually or following survival of cardiac event

Answer 41

Chronic HF

Question 42

Acute or chronic HF? | Adaptive mechanisms to improve cardiac performance

Answer 42

Chronic HF