Inotropic Drugs-Limitations in Heart Failure

Question 1

NE effects

Answer 1

↑ sympathetic outflow → NE effects on β-receptors (1 and 2) and α2 receptors on the myocardium

*downregulate β-1

Question 2

NE Response on:
□  β1, β2, α1 → 
□  β1, β2, α1 →  
□  β1, β2  → 
□  β1, β2  → 
□  β1 →

Answer 2

□ β1, β2, α1 → cardiac myocyte response
□ β1, β2, α1 → positive inotropic response
□ β1, β2 → positive chronotropic response
□ β1, β2 → myocyte toxicity
□ β1 → myocyte apoptosis

• too much response can lead to myocyte death/increased arrhythmias

Question 3

Benefits of β-blockers

Answer 3

§ Prevent downregulation of B1 receptor
§ Prevent Apoptosis/Oxidative stress
§ Prevent hypertrophy/fibrosis
§ Prevent increased arrhythmia potential

• b-blockers as shield: upregulate b-1 and prevent negative effects
• reduce mortality and increase EF

Question 4

When should treatment with a beta blocker be started?

Answer 4

1. Tx with a diuretic so that patient has minimal evidence of fluid retention.
2. Tx with an ACE inhibitor for at least 2 weeks.
3. No recent use of IV vasodialators or positive inotropic agents
4. Systolic blood pressure > 90 mmHg
5. Heart rate > 60 beats/min (unless tx with a pacemaker)
6. Absence of end-organ failure

Question 5

Neprilysin inhibitors

example

Answer 5

Valsartan
Sacubitril
L8Q657

Question 6

How does Neprilysin inhibitors work?

Answer 6

when we get additional stretch of atria or ventricles → get release of B-type natriuretic peptide (pro BNP) → converted N-terminal BNP → cleaved to BNP (which has awesome effects)

• well Neprilysin is a dick that degrades BNP. So Neprilysin inhibitors are cock blockers

Question 7

Beneficial Effects of BNP

Answer 7

○ Vasodilator reduces afterload
○ Reduces sympathetic tone
○ Reduces aldosterone
○ Natriuresis, diuresis

Question 8

HFrEF vs HFpEF

what type of dysfunction?

Answer 8

o Heart failure with reduced ejection fraction = HFrEF
- Left ventricular systolic dysfunction = LVSD

o HF with preserved ejection fraction = HFpEF
o Preserved systolic function = PSF
- Diastolic dysfunction

Question 9

Main Mechanism of Digoxin

Answer 9

○ Blocks Na/K ATPase, get accumulation of Na on intracellular side
§ NCX then swaps Na for Ca
§ Increase force of contraction
§ That’s why digoxin is thought of as a weak inotrope

○ Other mechanism of digoxin:
§ Neurohormonal modulator via baroreceptors

Question 10

Secondary mech of Digoxin

Answer 10

Neurohormonal modulator via baroreceptors
□ Indiv. can lose sensitivity when heart is overstimulated, symp nervous system is always on and para doesn’t respond well

Dig may increase parasymp activity by increasing sensitivity and decreasing symp sensitivity
*remember: digoxin is a weak inotrope that increases F of contraction

Question 11

How is digoxin excreted?
Half life?
Does it have a large or narrow therapeutic window?

Answer 11

Renally
38 hours: takes ~7 days to get to steady state
Narrow

Question 12

Which drugs used in conjunction of Digoxin will double it’s [ ]?
(meaning if you are using any of these agents, you have to drop dig levels by 50%)

Answer 12

Quinidine, 
varapamil, 
amiodarone, draniderone, Propafenone, 
itraconazole, 
arythromycin, 
Erythromycin, 
clarithromycin,

Question 13

Digoxin toxicity:

Answer 13

hypokalemia
hypercalcemia
hypomagnesemia

Question 14

How do patients present with Digoxin toxicity? (symptoms)

Answer 14

Neurological: weakness, confusion
Visual: sensitivity to light, yellow halos around eyes, blurred vision
Cardiac: bradycardia, heartblock, arrhythmias
GI: nausea vomiting, ab pain
Electrolyte: hyperkalemia

*recall: hypokalemia
hypercalcemia
hypomagnesemia

Question 15

role of digoxin in patients with HFrEF

Answer 15

Digoxin can be beneficial in patients with HFrEF, unless contraindicated, to decrease hospitalizations for HF

Question 16

Diuretics

• list some
• what do they do

Answer 16

Bumetanide
Furosemide
Torsemide

→ reduced fluid volume

Question 17

Inotropes

• list some
• what do they do

Answer 17

Dobutamine
Milrinone

→ augment contractility

Question 18

Vasodilators

• list some
• what do they do

Answer 18

Nitroglycerin
Nitroprusside
Nesiritide

→ decrease preload and afterload

Question 19

What does it mean when a pt is in :

• subset I “warm and dry”
• subset II “warm and wet”
• subset III “cold and dry”
• subset IV “cold and wet”

Answer 19

- subset I "warm and dry"
     Normal
- subset II "warm and wet"
     Congestion
- subset III "cold and dry"
     Hypoperfusion 
- subset IV "cold and wet"
     Congestion and hypoperfusion

Question 20

How do you warm up? How do you dry out?

Answer 20

Warm up: use inotrope (dobutamine, milrinone)

Dry out: use diuresis

Question 21

Dobutamine

Answer 21

b-1 agonist to increase contractility,

slight peripheral vasodilation

Question 22

Milrinone

Answer 22

PDE inhibitor, augments myocyte Ca utilization, moderate peripheral vasodilation

• indication: cold and wet

Question 23

Inotropic agents like Dobutamine and milrinone are used specifically to treat patients with:?

Answer 23

1. To relieve symptoms and improve end-organ function
2. Patients with marginal systolic blood pressure (<90 mm Hg)
3. Patients with symptomatic hypotension despite adequate filling pressure
4. Unresponsive to, or intolerant of, intravenous vasodilators.

Question 24

Dopamine MOA

Answer 24

endogenous precursor of norepinephrine-
excerts its effects by directly stimulating adrenergic
receptors, as well as, release norepi from nerve
terminals

Question 25

Dopamine benefits:

Answer 25

RIP!!!
○ R - Renal
	§ Dopaminergic, may improve renal output
○ I - Inotrope
	§ Beta receptor 
○ P - Pressor
	§  Alpha receptor

Dopamine acts on different types of receptors

Question 26

Dopamine adverse effects:

Answer 26

Arrythmic
Angina
Increased HR
Increased MAP