Ionotropic therapies/HF therapies

Question 1

___ is the original inotrope deriived from the foxglove plant

What is the mechanism of inotropy of this drug?

Answer 1

Digitalis (same thing as Digoxin) is the original inotrope deriived from the foxglove plant

Mechanism of action:

Inhibition of membrane Na/K ATPase >> increased intracellular Na+ >> reversal of Na/Ca exchanger (Na+ out, Ca2+ in) >> increased intracellular Ca2+ >> more calcium available for contraction >> greater force of contraction

Question 2

What are the non-inotropic effects of digoxin? (2)

Answer 2

Decreases sympathetic tone (increased carotid baroreceptor reflex) - lowers BP

Increased vagal tone - decreases AV conduction, atrial automaticity; prolongs absolute refractory period (so prolongs AP)

Question 3

What are the clinical indications of digoxin? (2)

Answer 3

Heart failure

A-fib/A-flutter

Question 4

Which groups of patients require inotrope therapy?(2)

Answer 4

Pts w/ acute decompensation of HFrEF

Folks w/ end stage HFrEF

Question 5

Describe the presentations of acute heart failure (3)

Answer 5

Wet and warm: fluid retention + normal perfusion

Wet and cold: fluid retention + worsening perfusion

Dry and cold: no volume excess + poor perfusion

**note that people with the wet and cold presentation (excessive fluid retention plus decreased perfusion) have the highest mortality**

Question 6

Review the pt case below. Why doesn’t Ms. H respond to the high dose IV diuretic?

Answer 6

Ms. H has a poor response to high dose IV diuretic because she has poor renal perfusion (there’s poor delivery to the kidneys, the drug probably won’t get there anyway so there’s no way she’s gonna be able to excrete excess sodium and water)

Question 7

What woud you give to acutely improve cardiac output in pts like Ms. H (case below)?

Answer 7

Recall that CO = HR x SV

Need to increase HR, or decrease afterload (SV), or increase contractility

Only option currently: catecholamines

*do NOT use digoxin*

Question 8

Name the sympathomimetics drugs you could use as inotropes

Answer 8

Dobutamine, dopamine (the other ones I, NE, E are less desirable as inotropes because they will increase HR and we don’t want to increase it any further)

PDE3 inhibitors (milrinone) (I think milrinone promotes the breakdown of cAMP such that there’s increased Ca2+ available for contractility)

Question 9

Describe the mechanism of action of dobutamine (and dopamine)

What is the MOA of milrinone?

Answer 9

Dobutamine binds to the beta 1 and beta 2 receptors >> activating AC >> increased cAMP >> PKA >> somehow promotes more Ca2+ for contractility

Milrinone prevents cAMP breakdown >> activation of PKA >> increased intracellular Ca2+ for contractility

Question 10

ICD’s are appropriate for pts with an EF of ___ or less

Answer 10

ICD’s are appropriate for pts with an EF of 35% or less

Question 11

If a pt with HFrEF also presents with LBBB, then ___ (treatment type) is recommended to improved HF symptoms AND decrease mortality

Answer 11

If HFrEF also presents with LBBB, then Bi-ventricular pacing (“BiV”) is recommended to improved HF symptoms AND decrease mortality

aka cardiac resynchronization therapy (they put in these little pacers or something into the coronary veins of both ventricles for more synchronous contractions)

Question 12

Since BiV pacing won’t be beneficial for a pt with HFrEF and a NORMAL ECG, what would you use to treat their condition? (improve dyssynchronous LV contractile pattern)

Answer 12

You would use an ICD (indicated for mortality benefit)

Question 13

What do you do for the pt who is dependent on inotrope infusion?

Answer 13

LVAD or heart transplant