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Flashcards in Cardiovascular Pharm II Deck (70):
1

What is heart failure associated with?

Decreased contractility

2

What does the decreased contractility in heart failure ultimately do

Tissues cant get enough O2 bc blood not pumping enough, this causing a sympathetic compensation

3

What things does the sympathetic system do to compensate for heart failure?

Increase arteriolar constriction (afterload)
Increase blood volume (preload)
Increase heart rate

4

Sympathetic compensation of heart failure: arteriolar constriction

Increases TPR-vascular resistance-increased afterload
-now heart has to constrict even harder against arterioles
-TX: want to decrease afterload so heart wont have to work as hard

5

Sympathetic compensation of heart failure: increased blood volume

-increased blood pressure
-this is a problem because the heart is already failing and now has to pump extra fluid around
-problem at the level of the veins
-preload increased (increased, end diastolic and increased venous return, all mean the same things)
-TX: want to decrease preload with diuretics or venodilate

6

Sympathetic compensation for Heart failure: increased HR

-leads to arrhythmia
-control this by decreasing HR
-do this with B1 blocker in low dose, because B1 blockers reduce HR AND contractility, and you do not want to decrease contractility in an already failing heart

7

Why do we use low does beta blocker in heart failure

Because it will Lower the heart rate without affecting contractility. If you give a higher does of B blocker, it could lower contractility, and we dont want that in an already failing heart

8

How does the heart compensate during failure?

-increased SANS activity
-myocardial hypertrophy
-increased RAAS

9

What do all of the compensatory actions of the heart during heart failure lead to

Cardiac remodeling
-fibrosis

10

What is the main target when trying to combat cardiac remodeling in cardiac failure

Aldosterone
-epi and NE are potential targets too, but aldosterone main one

11

If you something decreases remodeling, what else does it do

Increases survival

12

If something increases survival, what else does it do

Decreases remodeling

13

What is the main goal when treating someone with heart failure

Improve survival

14

Why is there an increase in heart failure today

Because more people are surviving heart attacks and are left with failing hearts instead of dying right away

15



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A Note Card- by Champ

16

What are the drugs used to treat CHF

1. RAAS inhibitors
2. B blockers
3. Diuretics
4. Inotripic drugs
5. Other vasodilators
6. If channel blocker

1-3 are the first line drugs, the others are back up

17

What are the type 3 drugs we use to treat CHF

1. RAAS inhibitor (ACEI or ARB, ACEI first)
2. B blocker (metoprolol)
3. Diuretics (loops and thiazides)

18

What is the very first drug usually given in CHF

ACEI

19

What is the second drug usuallygiven for CHF

Metoprolol

20

Why do we not give inotropic drug first for CHF?

Digoxin is very dangerous, and it’s the best option of them all. Don’t want to risk this with patients

21

What do diuretics do in CHF

Decrease fluid

22

What do ionotropic drugs do for CHF

Increase contractility

23

What is the only inotropic drug that is ok for chronic use

Digoxin

24

What are the two inotropic drugs that are for acute only when treating CHF?

B agonists
Phosphodiesterase inhibitors (inamrinone)

25

What are some other vasodilator that can be used for CHF treatment but are not first choice

-Neprilysin inhibitor (sacubitril)
-amlodipine (CCB)

26

What is considered first line therapy for CHF?

ACEI (and ARB but mostly ACEI)

27

Mechanism of ACEI in treating CHF

-inhibit the vasoconstriction effects of ANGII
-inhibit the retention of sodium and water by inhibiting aldosterone
-prevent aldosterone-mediated cardiac remodeling

28

Cardiovascular actions of ACEI in CHF

Preload is reduced
Afterload is reduced
Reduce the long term remodeling and therefore INCREASES SURVIVAL

29

What is the B blocker that is most commonly used for CHF

Metoprolol

30

Clinical use of metoprolol for CHF

-In combination with ACEI (+/- diuretics, +/- digoxin)
-decreasing mortality (INCREASED SURVIVIAL)
-decreased remodeling

31

Dosage of B blockers for CHF

Dosing is critical
-start with low dose and titration upwards
-high doses could be lethal
-if low does is not enough, you must supplement with another drug as opposed to increasing the dose

32

Other than decreasing HR, what other way can a low does B blocker be beneficial to a patient with CHF?

Blocks B1 on the kidneys, reducing renin
-decreases RAAS
-decreases aldosterone

33

MOA of diuretics in CHF

Reduce preload!!!
Good at lowering fluid

34

What diuretics are good at decreasing fluid for CHF?

Loops: furosemide
Thiazides: HCTZ

35

What do furosemide and HCTZ do for cardiac remodeling in CHF?

NOTHING!
These only work to decrease fluid

36

What diuretics are good at reducing adolsterone in CHF?

Spironolactone and eplerenone

37

What is the primary use of spironolactone and eplerenone?

Decrease aldosterone to decrease remodeling to increase survival

They are not very good diuretics when it comes to decreasing fluid and decreasing preload

38

What is the difference in the diuretics: furosemide and HCTZ vs spironolactone and eplerenone?

Furosemide and HCTZ are good diuretics at decreasing fluid and therefore decreasing preload

spironolactone and eplerenone are good at decreasing aldosterone to decrease remodeling to increase survival! They are not good diuretics when it comes to decreased fluid

39

What is the neprilysin inhibitor used for CHF

Sacubitril

40

An enzyme that degrades atrial and brain natriuretic peptide, two blood pressure-lowering peptides that worl mainly by reducing blood volume

Neprilysin

41

What does sacubitril (a neprilysin inhibitor) do

-Inhibits neprilysin (increase ANP and BNP levels)
-increases levels of bradykinin

42

What is an ARNI

Sacubitril + Valsartan

Angiotensin II receptor blocker neprilysin inhibitor

43

How do you take sacubitril?

You take it in combination with valsartan, called ARNI together

44

Adverse effects of sacubitrol

Cough and angioedema, due to the increased bradykinin

45

What is ivabradine

If (funny) sodium channel blocker

46

What is the If channel responsible for

The automaticity of the SA node; these channels are unregulated in heart failure patients

47

How does ivabradine (If channel blocker) work

-Decreasing the diastolic depolarization slope in the SA node, decreasing heart rate without direct effects on contractility
-used for patients in sinus rhythm with resting HR >70bpm and also taking B blockers at their highest tolerable dose

48

Ivabradine is used with what other drug

B blockers

49

If sodium channel blockers on HR and contractility

Decreases HR and does nothing to contractility

50

Does ivabradine replace B blockers?

No
Use WITH B blockers

51

CCB for heart failure

Pretty much don’t use them much but it is a last resort option
-amlodipine
-provide no mortality benefit

52

Digitalis

-Derived from the plant digitalis (foxglove)
-increase contractility of heart (positive inotropic effect)
-digoxin

53

Therapeutic index of digoxin

<2
Very toxic

54

MOA of digoxin (inotropic drug)

Reversible binds to the Na+-K+ ATPase of cardiac cells

55

How does digoxin cause increased contractiltiy ?

-Digoxin binds and inhibits Na+-K+ ATPase
-increases intracellular Na+
-increased intracellular Na leads to a greater Ca++ incflux
-Ca++ stored in SR
-more Ca++ now released when heart contracts, causing stronger contractility

56

When is digoxin contraindicated?

In patients with hypokalemia

57

Why is digoxin contraindicated in patients with hypokalemia?

Digoxin binds to the same site as the K+ on the Na+-K+ ATPase, competing.
-hypokalemia leads to more digoxin being able to bind
-huge problem leading to digoxin toxicity

58

When do you use digoxin?

When you cant control heart failure with the first three choice drugs

59

What are the adverse effects of digoxin?

Severe arrhhhmias
Nausea, vomiting, confusion, and blurred vision (CNS EFFECTS!)

60

What drug is someone proanbably on if they complain of yellowish halos and blurred vision?

Digoxin

61

Factors predisposing to digitalis toxicity

Hypokalemia

62

What drugs should be avoided when taking digoxin

Diuretics, they can be potassium wasting and cause digoxin toxicity

63

What drugs are only used for acute settings of heart failure, such as in the hospital

B agonists
Phosphodiesterase inhibitors

64

B agonists and congestive heart failure

Positive inotropic effects, but used only short term due to tachypylaxis (rapid tolerance)

65

What is the B agonist we use for acutely for heart failure

Dobutamine
-actions on B1 receptors and enhances cardiac contractiltiy

66

Phosphodiesterase inhibitors and heart failure

-Only in hospital (acute)
-short term
-mortality with long term use

67

How does phosphodiesterase inhibitor work?

B receptors stimulation causes production of cAMP, which causes protein kinase A increase, which phosphorylation the Ca2+ channel to open it

Phosphodiesterase inhibitors stop the PDEIII from breaking down cAMP, so that it can open more Ca2+ channels

Only want to do this short term
Opposite of a B blocker

68

How does a B agonist increase contractility?

Increase of Ca++ into the cell, goes to SR, more Ca++ released for contraction

69

What is the phosphodiesterase inhibitor we use for heart failure

Inamrinone

70

What drug increases cAMP?

Phosphodiesterase inhibitor (inamrinone)