43-44 Mech of HF and Drugs

Question 1

What are the three cardinal manifestations of HF?

Answer 1

dyspnea, fatigue, fluid retention

[not all patients have fluid overload and thats why they don’t call it congestive HF anymore]

Question 2

T-F– heart failure can occur when CO is high or low?

Answer 2

True

Question 3

What are the 4 causes mentioned of HF when CO is high?

Answer 3

hyperthyroidism
beriberi
anemia
major AV shunts

Question 4

Increased force of contraction is produced when?

Answer 4

increased sarcomere length during diastole- closely related to end diastolic filling pressure (pre-load)

Question 5

What is the inotropic state of the heart-

Answer 5

contractile state of the heart determined by its contractile properties and influence of autonomic nerves and circulating catecholamine which can also influence HR

Question 6

What protein pumps CA into the sarcoplasmic reticulum? out of the SR?

Answer 6

SERCA

RyR2

Question 7

What proteins pump CA out of the cell?

Answer 7

Ca ATPase

NCX polarized

Question 8

What pumps Ca into the myocyte during the depolarized state.

Answer 8

L-type Ca channel

Question 9

What happens to the NCX Na/Ca exchanger during depolarization ?

Answer 9

breifly reverses so Ca goes into the cell

Question 10

In heart failure what is systolic dysfunction? diastolic dysfunction?

Answer 10

1. abnormally weak contraction during systole
2. abnormal relaxation during diastole
   [remember they can be individual or in combination]

Question 11

T-F– energy delivery, production and storage and energy utilization are thought to be heavily involved in pathogenesis of failure?

Answer 11

False-not involved

Question 12

What are 5 signs and symptoms of HF?

Answer 12

1. numerous hemodynamic abnormalities
2. dysregulation of Ca homeostasis- impair contraction and relaxation
3. dysreg of contractile proteins and interferes with cross bridge recycling
4. densensitized b adrenergic pathway–> reduced Ca uptake in SR.
5. myocytes lost by cell death–>fibrosis

Question 13

Reduction in CO does what?

Answer 13

activates SNA and RAS and increases venous volume

Question 14

Increases in intravascular and ventricular volumes leads to what?

Answer 14

increased diastolic and systolic wall stress, leading to hypertrophic remodeling of the hear and impaired contraction

Question 15

Neurohumoral mediated increases in arterial and venous constriction increase what?

Answer 15

ventricular after load and preload respectively

Question 16

Neurohumoral activation (SNA, ANGII, and aldosterone) act directly on the myocardium to promote what?

Answer 16

Unfavorable remodeling via myocyte apoptosis and changes in gene expression and EM composition

Question 17

Reduced function of both arterial and venous baroreceptors leads to what?

Answer 17

increased activity of SNA, RAS, and vasopressin

Question 18

T-F–hypertrophied heart operates at a higher inotropic state?

Answer 18

False- lower

Question 19

What happens in renal function due to sympathetic- induced vasoconstriction ?

Answer 19

Shunts blood from glomeruli, stimulates renin, –>NA retention, increased blood volume, edema

Question 20

SNS RAS and vasopressin all react to sustain arterial pressure with low cardiac out put by what? good or bad?

Answer 20

1. increasing peripheral resistance

2. Not beneficial

Question 21

What is the first thing we must do in the pharmacological treatment of HF?

Answer 21

correct any reversible causative factors

[arrythmias, hypertension, valve defects, anemia, thyrotoxicosis etc.]

Question 22

AHA stage A and B include who? C and D?

Answer 22

at risk for heart failure

with heart failure

Question 23

What is stage A? Drugs usually used?

Answer 23

1. at risk but w/out structural heart disease or symptoms

2. ACEI or ARBS

Question 24

What is stage B? Drugs typically used?

Answer 24

1. Structural heart disease but without signs or symptoms

2. ACEI or ARB and Beta blockers

Question 25

What is stage C? What drugs typically used/

Answer 25

1. structural heart disease with prior or current symptoms | 2. diuretics, ACEI and beta blockers

Question 26

What is stage D HF? Tx?

Answer 26

1. refractory HF requiring specialized interventions 2. drugs from classes A,B,C, end of life care, and extraordinary measures (transplant, inotropes, mechanical support, experimentals)

Question 27

What drugs do we use for after load reduction?

Answer 27

ACEI, ARBs, isosorbide dinitrite or hydalazine

Question 28

What diuresis drugs do we use for HF?

Answer 28

loop diuretics and thiazides, spironolactone

Question 29

What drugs do we use for positive isotropy?

Answer 29

adrenergic agoinsts cAMP phosphodiesterase inhibitors digitalis glycosides

Question 30

What are the only drugs to date that have reduced mortality when used alone?

Answer 30

ACEI ARB beta blockers

Question 31

How do beta blockers effect renin?

Answer 31

block renin release

Question 32

What molecules do ACEI suppress?

Answer 32

Ang II, Ang III, and aldosterone

Question 33

What do ACEIs prevent degradation of?

Answer 33

bradykinin [potent vasodilator]

Question 34

Are ACEIs more potent arterial or venous dilators?

Answer 34

Arterial- effects after load and CO

Question 35

ACEI are often first line therapy and should be prescribed to all patients with what?

Answer 35

reduced LVEF | [often used in combination with beta-blocker]

Question 36

T-F-- survival benefit in patients with mild-moderate and moderate-severe HF in patients taking enalapril compared to isosorbide dinitrite/hydralizine?

Answer 36

True

Question 37

T-F--ACEI prevent progression of HF in patients after MI?

Answer 37

True

Question 38

T-F--ARBs allow for residual AT2 receptor stimulation by AngII and AngIII to promote vasoconstriction and diuresis?

Answer 38

False- vasodilation and natriuresis

Question 39

Is there incremental benefit of combining ARBs and ACEIs?

Answer 39

No

Question 40

T-F-- in HF the kidney retains Na and water allowing the heart to operate at higher EDV to maintain LV stroke volume? what does this lead to?

Answer 40

True- increase end diastolic filling pressure leading to ventricular remodeling, pulmonary venous congestion and edema

Question 41

Because patients with HF operate on a plateau phase on the starling curve, pre-load reduction can occur without what?

Answer 41

decreases in cardiac output

Question 42

How do diuretics improve symptoms of congestive hear t failure?

Answer 42

moving patients to lower cardiac filling pressures along the same ventricular function curve

Question 43

When might thiazides be preferred over loop diuretics in HF?

Answer 43

in hypertensive patients

Question 44

T-F--diuretics produce symptomatic benefits more rapidly than any other drug for heart failure?

Answer 44

Yes- hrs or days vs weeks to months for ACEIs and Bblockers

Question 45

When should diuretics not be used alone?

Answer 45

in patients with stage C heart failure

Question 46

Do diuretics have a strong mortality benefit in heart failure?

Answer 46

No

Question 47

Is heart failure characterized by sympathetic hypo activation?

Answer 47

No hyperactivity

Question 48

Do beta blockers benefit inotropic performance?

Answer 48

No they impair it, but they improve symptoms, exercise tolerance, and increase LVEF in HF over months

Question 49

Improvement of abnormal Ca2+ handling may occur with beta antagonists how?

Answer 49

possibly by preventing hyperphosphorylation of the Ryanodine receptor which causes diastolic leak of Ca2+ from SR

Question 50

Beta blockers should be given to all patients with HF due to reduced LVEF unless what?

Answer 50

they are contraindicated (bradycardia or reactive airway disease)

Question 51

Has carvedilol been associated with a significantly reduced mortality compared with metoprolol?

Answer 51

Yes

Question 52

How does digoxin increase the force of cardiac contraction ? What does this do to renal perfusion?

Answer 52

1. increasing intracellular free Ca2+ | 2. up CO--> decr SNA and increases renal perfusion

Question 53

Where do cardiac glycoside binding occur?

Answer 53

Na/K ATPase

Question 54

What are dioxins two main effects in non-cardiac tissues?

Answer 54

1. sensitizes cardiac barorecepotrs --> decr. sympathetics and increase para 2. Inhibit Na/K pump in kidney--> reduces renin release

Question 55

Is digoxin a first line therapy?

Answer 55

NO NO NO!! maybe with patients in atrial fibrillation, or those with persistent symptoms despite therapy with diuretics, ACEI and beta blocker

Question 56

Can digoxin toxicity be treated ?

Answer 56

yes with digoxin immunotherapy

Question 57

Does digoxin show a strong effect of increased survival in HF?

Answer 57

No- actually increased risk of death due to arrythmias or MI

Question 58

can aldosterone exert adverse effects on the heart independently and in addition to deleterious effects produced by AngII?

Answer 58

YEs

Question 59

Addition of aldosterone antagonist should be considered when in HF?

Answer 59

moderately severe HF with left ventricular dysfunction after MI- need to use concomitant diuretic therapy

Question 60

Do arteriodilators decrease systemic vascular resistance and increases renal perfusion/diuresis?

Answer 60

Yes

Question 61

Is isosorbide dinitrite usually used in combination with something?

Answer 61

Yes- hydralazine-- because it is not as effective as an arteriodilator

Question 62

Can hydrazine reduce renal vascular resistance and increase renal blood flow?

Answer 62

yes

Question 63

How is sodium nitroprusside and nitroglycerin given in HF?

Answer 63

usually acute setting by IV [parenteral]

Question 64

Are inotropic agents used long term?

Answer 64

No- acute use only

Question 65

Does dobutamine activate dopamine receptors?

Answer 65

No

Question 66

Do cAMP phosphodiesterase inhibitors stimulate just venous dilation?

Answer 66

No- both arterial and venous