Heart Failure Treatment 2

Question 1

Cardiac glycosides drugs

Answer 1

Digoxin (Lanoxin, Lanoxicaps)

Question 2

Cardiac glycoside MOA

Answer 2

Inhibition of Na/K ATPase via preferential binding to the phosphorilated alpha subunits and inhibiting it

Question 3

Extracellular K does what

Answer 3

Promotes de-phosphorylation of the alpha subunits which decreases the effectiveness of cardiac glycosides

Question 4

How does contraction happen in cardiomyocytes?

Answer 4

Impulse leads to sodium entering through the fast sodium channels –> triggers an exchange of calcium and sodium which then leads to a huge amount o calcium to enter through L type channels
Calcium also comes from the sarcoplasma reticulum which leads to a ton oc Ca within the cell
This calcium then interacts with troponin or calmodulin which leads to phosphorylation of myosin light chain kinase which leads to interaction of actin and myosin which leads to contraction of the cells

Question 5

How does relaxation occur in cardiomyocytes?

Answer 5

Sodium leaves the cell and potassium enters (3:2) via Na/K ATPase and the calcium leaves the cells and then leftover Ca is stored sarcoplasm reticulum
This leads to no phosphorylation and actually have de-phosphorylation

Question 6

So where do cardiac glycosides come in on all of this?

Answer 6

They block the Na/K ATPase and other cells that let Ca out so this calcium is moved into the sarcoplasma reticulum and then less Ca has to come in to the cell which leads to a stronger contraction than before

Question 7

Cardiac glycoside main effect

Answer 7

+ Inotropic effect
Increased vagal tone and decreased sympathetic activity
Increased AV refractory period

Question 8

What does vagus activation do?

Answer 8

The heart slows down, which can be a good thing because it will rest during diastolic and during systolic it will contract with more force

Question 9

Increased AV =

Answer 9

It takes longer for impulses to travel through heart and this is good because the heart rate will be lower

Question 10

Ions and cardiac glycoside actions:

Answer 10

K+- promotes alpha subunit dephosphorylation in Na/K ATPase and decreased interation of cardiac glycosides with the pump
Hypercalcemia increases digoxin toxicity
Hypomagnesemia increases digoxin toxicity

Question 11

Hypokalemia

Answer 11

potentiates digoxin effects, as well as toxicity

Question 12

Hyperkalemia

Answer 12

Attenuates digoxin effects on the heart

Question 13

Digoxin’s therapeutic window

Answer 13

Very narrow

• Effective: 0.5-1.5
• Toxicity: ~1.5

Question 14

Digoxin special features

Answer 14

Unchanged in urine

- Can cause cardiac arrhythmias, anorexia, n/v, blurred vision and seizures

Question 15

Dobutamine

Answer 15

Beta agonists in systolic dysfunction and HF

Stimulates B1 and B2 and alpha 1 antagnoist and agonists so this neutrilizes

Question 16

Dobutamine Ultimately does what

Answer 16

Increase stroke volume via beta 1
slightly increases HR via beta 1
Modest decrease in peripheral resistance via beta 2

Question 17

Dobutamine AE

Answer 17

Tachycardia and arrhythmias

Tolerance may develop

Question 18

Epinephrine

Answer 18

Has beta and alpha activity but the beta is much more prevalent

Question 19

Epinephrine does what?

Answer 19

Increase strength of contractility
Increase AV node conductance
Increase HR
(No change in peripheral resistance

Question 20

Epinephrine has metabolic effects which

Answer 20

effects the lungs and airways as well as the eyes (via B2)

Question 21

Epinephrine AE

Answer 21

HTN
Headache
Anxiety/confusion
Angina

Question 22

Norepinephrine activity and does what?

Answer 22

Alpha and beta but more alpha

It causes vasoconstriction which increase peripheral resistance and may slightly increase or not change CO

Question 23

Dopamine Low Doses

Answer 23

Less 2 mcg/kg/min
D1 receptors in vasculature causing vasodilation
Presynaptic D2 receptors causes decrease NE release
Direct effect on renal tubular epithelial cell causing increase natriuresis

Question 24

Dopamine intermediate dose

Answer 24

2-5mcg/kg/min

Directly stimulate beta receptors in the heart and nerve terminal to increase cardiac contractility and NE release

Question 25

Dopamine High Dose

Answer 25

5-15 mcg/kg/min

Stimulates alpha 1 receptors in the vasculature to cause vasoconstriction

Question 26

Dopamine AE

Answer 26

Etopic beats, tachycardia, angina, HYPOtension, headache nausea

Question 27

Milrinone (Primacor)

Answer 27

Short term support advanced HF
Increases cardiac contractility and decreases peripheral resistance
Selectively inhibits PDE in the myocardium and vasculature so it doesn’t not inactivate cAMP

Question 28

B-agonist + Milirone

Answer 28

Increased effects

Question 29

B-antagonists + B-agonists

Answer 29

No effect

Question 30

B-antagonists + milrinone

Answer 30

Slightly increased effect

Question 31

Stimulation of B1 and B2 lead to

Answer 31

Increase adenylyl cyclase and increase cAMP

Question 32

Milrinone AE

Answer 32

Arrhythmia, hypotension, headache, thrombocytopenia

Question 33

Myocardial injury + continuous SNS activation

Answer 33

Contributes to progression of contractile dysfunction

Question 34

Prositive inotrope agents are predominantly used for

Answer 34

Acute HF (short term support of circulation

Question 35

Beta adrenergic antagonists do what

Answer 35

Block harmful effects of activated SNS

Used to treat mild-to-moderate HF

Question 36

Examples of Beta adrenergic antagonists in HF

Answer 36

Metoprolol (Toprol, Lopressor) and Carvedilol (coreg)

Question 37

Metoprolol activity

Answer 37

Selective beta 1 adrenoceptor antagonist

Question 38

Carvedilol activity

Answer 38

B1/2 and alpha 1 adrenergic receptor antagonists

+ Calcium channel blocking activity