Treatment Of Congestive Heart Failure

Front 1

What is the MOA of Cardioglycosides?

Back 1

They increase the strength of cardiac contraction.

Front 2

What is the MOA of phosphodiesterase inhibitors?

Back 2

They increase the strength of cardiac contraction.

Front 3

What is the MOA of sympathomimetric agents?

Back 3

They increase the strength of cardiac contraction.

Front 4

What is the MOA of calcium sensitizers?

Back 4

They increase the strength of cardiac contraction.

Front 5

Describe the mechanism for drugs that increase the strength of cardiac contraction.

Back 5

Drugs with direct positive inotropic effects
These drugs have direct positive inotropic effects. They Increase in contractility --> ↑ CO --> improve perfusion of organs

Front 6

What are the goals of drugs that treat CHF?

Back 6

alleviate symptoms
improve quality of life
arrest cardiac remodeling
prevent sudden death

Front 7

What are the problems that occur with CHF?

Back 7

Reduced force of contraction
Decreased cardiac output
Increased TPR
Inadequate organ perfusion
Development of edema
Decreased exercise tolerance
Ischemic heart disease
Sudden death

Front 8

Name the drugs that are used to treat CHRONIC heart failure

Back 8

ACE inhibitors
Beta-blockers
ATII antagonists
aldosterone antagonists
Digoxin
Diuretics

Front 9

What are the drugs used to treat ACUTE heart failure?

Back 9

diuretics
PDE inhibitors
vasodilators

Front 10

The best of all the drugs for Acute heart failure is....

Back 10

PDE Inhibitor

Front 11

What drug is useful to treat BOTH Acute and Chronic Heart Failure?

Back 11

Diuretics

Front 12

What are the drugs classes that we can use to treat heart failure in general?

Back 12

1. Drugs increasing the strength of the cardiac muscle contraction

2. Diuretic agents

3. ACE inhibitors (reduce both preload and afterload)

4. Other vasodilators

5. beta-blockers

6. Antiarrhythmic agents occasionally are required to normalize cardiac rate and rhythm

Front 13

What do diuretic agents do?

Back 13

1. decrease extracellular fluid volume (decrease preload and congestion-edema)

2. antagonize aldosterone receptors

Front 14

Where are cardiac glycosides derived from and which plants?

Back 14

1. Strophanus - Ouabain
2. Digitalis lanata - Digoxin, Digitoxin

Front 15

What does Cardiac Glycosides do?

Back 15

1. increase force of myocardial contraction
2. alters electrophysiological properties

Front 16

What is the most common cardiac glycoside?

Back 16

Digoxin

Front 17

What is the MOA of cardiac glycosides? How do we get a stronger HB?

Back 17

-inhibit Na/K pump --> increase intracellular Na --> increases Na/Ca exchange --> increase intracellular Ca --> stimulus come along and we increase Ca release from sarcoplasma reticulum --> more calcium available overall --> heart beat stronger

Front 18

Besides increasing the strength of contraction, how do cardiac glycosides increase the electrophysiological effects?

Back 18

Indirect effects

-->increased parasympathetic tone

--> decreased SA/AV node automaticity

--> decreased AV node conduction velocity & increased refractory period

--> net effect: decrease HR & impair impulse transmission in AV node

Front 19

Can cardiac glycosides stop disease progression or prolong life?

Back 19

No, just improves quality of life

Front 20

When can cardiac glycosides also be effective? (what disease can it treat primarily and secondarily)

Back 20

CHF secondary to ischemic heart disease.

Front 21

Describe the bioavailability and dosing of digoxin.

Back 21

Since it has a long half-life (24-36 h): once daily dosing, it has a high bioavailability from oral dosing and therefore a large volume of distribution

Front 22

How is digoxin excreted? How is DIGITOXIN metabolized?

Back 22

digoxin is excreted in kidneys and digitoxin is metabolized in liver, active metabolites

Front 23

Can Digoxin or Digitoxin be toxic? How?

Back 23

intestinal flora can cause variations in toxicity

Front 24

Comparing digoxin and digitoxin, digitoxin has a higher....

Back 24

1) protein binding
2) onset of action
3) half life

Front 25

What kind of digitalis toxicity is most common? Why?

Back 25

Potassium toxicity.

digitalis competes for K+ binding site on Na+/K+ ATPase. Therefore, it is contraindicated with K+ depleting diuretics or patients with hypo/hyperkalemia

hypokalemia: increased toxicity

hyperkalemia: decrease toxicity

Front 26

Drugs interacting with digoxin and other digitalis glycosides that can increase digitalis concentration are....

Back 26

Amiodarone
Erythromycin
Quinidine
Tetracycline
Verapamil

Front 27

Drugs interacting with digoxin and other digitalis glycosides that DECREASE LEVELS OF BLOOD POTASSIUM ARE...

Back 27

Corticosteroids
Thiazide diuretics
Loop diuretics

Front 28

How does Quinidine interact with Cardiac Glycosides?

Back 28

reduces the renal clearance of digoxin (competition for renal excretion) and displaces digitalis from tissue protein --> increases the toxicity of digoxin

Front 29

How does Verapamil, amiodaron, spironolakton interact with cardiac glycosides?

Back 29

displace digoxin from protein --> increase digoxin by 50-75 % (it may be necessary to reduce dose)

Front 30

What diseases are predisposing factors to digitalis toxicity?

Back 30

Hypothyroidism, hypoxia, renal failure, and myocarditis

Front 31

What are the vision effects of Digitalis?

Back 31

yellow-tinted vision or yellow corona-like spots

Front 32

Positive Inotropic agents are used in what situations due to their mechanisms and risks?

Back 32

ACUTE HF arising from the surgery or shocks (cardiogenic, septic)
SEVERE ACUTE DECOMPENSATION of chronic HF with signs of organ hypoperfusion

Front 33

What are phosphodiesterase inhibitors used for?

Back 33

primarily used for management of acute heart failure

Front 34

What effect does Phosphodiesterase inhibitors have overall on the CVS?

Back 34

1) increase rate of myocardial relaxation
2) decrease total peripheral resistance and afterload

Front 35

Describe the mechanism of action of phosphodiesterase inhibitors.

Back 35

Mechanism of action: inhibit phosphodiesterase --> increase cyclic AMP --> increase protein kinase --> increase contractility in the heart

But peripherally it can cause relaxation of smooth muscle

Front 36

name 2 phosphdiesterase inhibitors. Which once is more potent.

Back 36

Amrinone (Inocor) and Milrinone (Primacor)

Milrinone is a more potent phosphodiesterase inhibitor.

Front 37

how are aminrone and milrionone administered and are they effective on patients taking beta blockers?

Back 37

They are administrated IV and yes they are effective on those pts taking beta blockers

Front 38

What are the side effects of phosphodiesterase inhibitors? Because of these side effects, when do we prescribe them?

Back 38

1.sudden death secondary to ventricular arrhythmia
2. hypotension
3. Thrombocytopenia (Milronone does not effect platelets
4. Long term clinical trials associated with increased adverse effects and increased mortality

They are now only prescribed for acute cardiac decompensation in patients NON-RESPONSIVE to diuretics or digoxin

Front 39

Are Milrinone and Amrinone good long term? Why or Why not?

Back 39

NO!!!! Milrinone showed increased mortality and no beneficial effects.

Amrinone did not reduced the incidence of sudden cardiac death or prolong survival in patients with CHF !!!!!!

Front 40

What are Beta-adrenergic receptor antagonist treated for?

Back 40

standard therapy for treatment of CHF

Front 41

What are the advantages of beta-blockers over other drugs?

Back 41

reduce sudden death caused by other drugs and they are cheap

Front 42

What is Carvedilol? What are its effects?

Back 42

Type of beta-blocker that has a combination effects (beta –Blocker and selective alpha 1 blocker- may also block Ca channels)

Front 43

What is the mechanism of action of beta blockers?

Back 43

The mechanism is still unclear

It antagonizes β-adrenergic receptors on cardiac myocytes --> counterbalances increased SNS activity in CHF

- prevents development of arrhythmias
- reduces cardiac remodeling
- prevents renin release

Front 44

How are beta-blockers administered? What drugs is it given in conjuction with?

Back 44

Its administered orally. Its given in conjuction with Ace inhibitors and Digoxin.

Front 45

What classes are beta-blockers most useful in?

Back 45

Class 2 and Class 3 pts with chronic systolic heart failure.

Front 46

What are the side effects of beta blockers?

Back 46

1. cardiac decompensation
2. bradycardia
3. hypoglycemia
4. cold extremeties
5. fluid retention
6. fatigue

Front 47

What are direct acting sympathomimetics?

Back 47

1. causes immediate increases in cardiac inotropy

2. goal: to increase cardiac output but not effect total peripheral resistance

3. used in treatment of acute life-threatening CHF

Front 48

What is the MOA of Norepinephrine/epinephrine?

Back 48

increase CO, increase TPR

Front 49

What is the MOA of Dopamine?

Back 49

1. activates prejunctional D2 dopamine receptors, inhibit NE release of sympathetic nerves, vasodilation

2. activates cardiac β1- adrenergic receptors, increase cardiac output

Front 50

What is MOA of Dobutamine?

Back 50

1. stimulates β1-adrenergic receptors

2. peripheral vasodilation with minimal HR effects

Front 51

When is Dopamine used?

Back 51

1. used in cardiogenic, traumatic or hypovolemic shock

2. used with furosemide in diuretic resistant patients (volume overload)

Front 52

What are the side effects of direct effect sympathomimetrics?

Back 52

- restlessness
- tremor
- headache
- cerebral hemorrhage
- cardiac arrhythmias
- used with caution in patients taking β-blockers
- can develop dobutamine tolerance

Front 53

What are sympathomimetric drugs commonly used for?

Back 53

ACUTE CHF!

Front 54

What are ACE inhibitors commonly used for?

Back 54

CHRONIC CHF

Front 55

Name a few Ace inhibitors

Back 55

Captopril and Enalopril the "pril" drugs

Front 56

Name a few Angiotensin 1 inhibitors.

Back 56

Lorsartan and Valsartan, the "artan" drugs

Front 57

What is the MOA of Ace inhibitors?

Back 57

inhibits angiotensin converting enzyme (ACE)
prevents conversion of ATI to ATII

Front 58

What is the MOA of AT1 receptor antagonists?

Back 58

selectively inhibits ATI receptor activation

Front 59

What are the overall effects of BOTH Ace Inhibitors and AT1 receptor antagonists?

Back 59

decreased preload
decreased afterload
decreased cardiac remodeling
decreased SNS effects

Front 60

What drugs are useful in increasing LONG TIERM survival from CHF?

Back 60

Ace Inhibitors/At1 receptor antagonist drugs

Front 61

What are Ace Inhibitors useful for slowing down?

Back 61

slows progression of left ventricular dysfunction in CHF

Front 62

How are AT1 receptor antagonist different than Ace Inhibitors in terms of Effectiveness? Are AT2 still active? What do they control? How do you increase the effectiveness of AT1 inhibitors?

Back 62

- more effective then ACE inhibitors
- AT2 receptors still active: vasodilation, antiproliferative effects
- used in conjunction with ACE inhibitors for increased effectiveness

Front 63

What are the side effects of Ace Inhibitors and AT1 receptor antagonists?

Back 63

ACE inhibitors
- cough
- angioneurotic edema
- hypotension
- hyperkalemia

ACE inhibitors and ATI receptor antagonists are both teratogenic so pregnant women shouldn't take them.

Front 64

What are the goals of Vasodilators?

Back 64

Goal: reduce TPR without causing large decrease in BP

Front 65

What are the effects of Vasodilators?

Back 65

reduce preload
reduce afterload
relieves symptoms
increase exercise tolerance

Front 66

What are the drugs that are NO Donors? When are they used?

Back 66

Nitroglycerin and Isosorbide dinitriate/hydralazine.

They are used in ACUTE CHF.

Front 67

Describe the properties of Nitroglycerin.

Back 67

orally active
also administered I.V. for peripheral vasodilation
quick onset for acute relief

Front 68

Describe the properties of Isosorbide/dinitrate/hydralazine

Back 68

1. chronic administration for long-term symptom relief
2. administered I.V (like Nitroglyercin)

Front 69

What are Nesiritide properties.

Back 69

1. recombinant brain-natriuretic peptide (BNP)
2. BNP is secreted from ventricular myocytes in response to stretch

Front 70

What are the effects of Nesiritide?

Back 70

1. vasodilator: increases cGMP in SMCs
2. decrease afterload/preload
3. inhibits cardiac remodeling
suppresses aldosterone secretion

Front 71

How is Nesiritide administrated?

Back 71

administered IV for acute decompensated CHF

Front 72

What are the adverse effects of Nesiritide?

Back 72

hypotension, renal failure

Front 73

What are Diuretics primarly use for? Can you use it in emergency situations? How?

Back 73

1. primarily used in patients with acute CHF with volume overload

2. IV infusion causes immediate and predictable diuresis for immediate relief -> can use in emergency situation

Front 74

What is the goal of Diuretics?

Back 74

Goal: reduce preload/afterload

Front 75

What are the potential adverse effects of Diuretics?

Back 75

overdosing can result in excessive reduction in preload, overreduction in stroke volume

Front 76

What are the two most common Diuretics?

Back 76

thiazide and loop diuretics (i.e. Furosemide) commonly used as adjunct therapies in CHF

Front 77

What does Aldosterone do? How does it increase in levels? What are its effects?

Back 77

1. elevated AngII levels increase production of aldosterone in the adrenal cortex (~20X increase)

2. aldosterone activates mineralocorticoid receptors in renal epithelial cells in kidney

3. aldosterone promotes
- Na+ retention, Mg2+ and K+ loss
- increased SNS activity
- decreased PSNS activity
- myocardial/vascular fibrosis

Front 78

What are the uses of Aldosterone Antagonists?

Back 78

Goal: inhibit aldosterone negative effects in CHF

Front 79

Name examples of Aldosterone Antagonists.

Back 79

spironolactone
eplerenone

the "one" drugs

Front 80

What are the effects of Aldosterone antagonists? What can they be used with? What kind of patients can I use this drug with?

Back 80

1. reduce mortality in patients with moderate to severe CHF

2. only use in patients with normal renal function and K+ levels

3. use with K+ sparing diuretic

Front 81

What are the side effects of Aldosterone Antagonists?

Back 81

hyperkalemia
agranulocytosis
anaphylaxis
hepatoxicity
renal failure

Front 82

What are specific side effects of Spironolactone

Back 82

gynecomastia, sexual dysfunction

Front 83

What are specific side effects of Eplerenone

Back 83

arrhythmia, myocardial infarct/ischemia

Front 84

What kind of drug is Levosimendan?

Back 84

Calcium Sensitizer

Front 85

When do you treat a pt with Leveosimendan? What are the major effects?

Back 85

Indication: i.v. for treatment acute decompensations of CHF


Major effects – sensitizing troponin C to calcium and vasodilatation (also some antiischemic effects)


No major proarrhythmogenic effects


Increased contractility without worsening Ca2+ metabolism and increased O2 demands

Front 86

What are the major adverse reactions with Calcium sensitizers? Why are they not used widely today?

Back 86

Adverse reactions: hypotension, headache
↑ costs !!! so not widely used.