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Medical Pharmacology Exam 3 > Drugs for treatment of Heart Failure > Flashcards

Drugs for treatment of Heart Failure Flashcards

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USMLE® Step 1 flashcards
1
Q

What are the 3 cardinal manifestations of heart failure?

A

Dyspnea (shortness of breath)
Fatigue
Fluid Retention

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2
Q

In most conditions, heart failure is associated with decreased cardiac output. What are 4 examples where cardiac output is high, but metabolic demands are also high, resulting in heart failure?

A

Hyperthyroidism
Beri Beri
Anemia
Major AV shunts

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3
Q

What are the 4 levels of heart failure?

A 
• I – only at levels of exertion that would limit
normal individuals
• II – on ordinary exertion
• III – on less-than ordinary exertion
• IV – symptoms of heart failure at rest
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4
Q

What is the major determinant of contraction force?

A

Sarcomere length during diastole

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5
Q

What is the major determinant of sarcomere length?

A

End diastolic filling pressure (pre-load)

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6
Q

What are preload and afterload relative to cardiac function?

A

Pre - Diastolic filling pressure

After - Arterial pressure (resistance heart pumps against)

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7
Q

Cardiac myocyte depolarization results in _ (ion) influx into the cell. This influx causing a change in membrane potential, stimulating calcium influx through _ type calcium channels. This influx causes more calcium release from the sarcoplasmic reticulum via _ receptors

A

Sodium
L-type
Ryanodine receptors

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8
Q

What happens to the Na/Ca exchanger during depolarization? How is calcium removed to the sarcoplasmic reticulum? How is the remaining calcium removed?

A

Briefly reverse, now calcium pumped into cell
SERCA, Calcium ATPase
Sarcolemmal Calcium ATPase

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9
Q

What are 2 components of heart failure that may be present individually or in combination?

A

Systolic dysfunction: Weak contraction

Diastolic dysfunction: Incomplete relaxation (not enough filling)

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10
Q

One of the earliest steps in heart failure is a reduction in cardiac output. What are 2 compensatory systems activated as a result of this reduction?

A

Sympathetic NS

Renin Angiotensin System

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11
Q

What are the major forces that cause cardiac remodeling during heart failure?

A

Increased intravascular and ventricular volume, leading to increased diastolic and systolic wall stress

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12
Q

What are 3 neurohumoral factors that act directly on the myocardium to promote unfavorable remodeling?

A

Sympathetic NS
Ang II
Aldosterone

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13
Q

What happens to the baroreceptor reflex during heart failure? What is increased as a consequence (3)?

A 
Reduced function (reads high pressures as normal)
Sympathetic NS, Renin-Ang system, vasopressin
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14
Q

Cardiac hypertrophy occurs during heart failure. Why is a larger heart deleterious?

A

A bigger heart operates at a reduced ionotropic state

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15
Q

How is the renin angiotensin system altered during heart failure? Why?

A

Increased renin release

Increased symp. NS shunts blood from glomeruli, stimulating renin release

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16
Q

What are 3 systems at work to sustain arterial pressure, despite decreased cardiac output during heart failure?

A

Symp NS
Renin Ang System
Vasopressin

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17
Q

What is the effect of increased venous pressure during heart failure?

A

Reduced capillary return, edema

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18
Q

What is the difference between stage A/B and stage C/D of heart failure?

A

Stage A/B - At risk for heart failure

Stage C/D - Have heart failure

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19
Q

How are stage A and stage B heart failures different? How do their treatments differ?

A

A - Risk, no symptoms (ACE inhib., Ang receptor Blockers)

B - Structural disease, no symptoms (ACE inhib., Ang receptor Blockers, beta blockers)

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20
Q

What is stage C heart failure? How is it treated?

A

Structural disease with current / prior symptoms

Diuretics, ACE inhibs, beta blockers

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21
Q

What is stage D heart failure? How is it treated?

A

Refractory heart failure

Requires extraordinary measures (transplant, mechanical support, etc)

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22
Q

What are 3 drug classes that can be used to reduce afterload?

A

ACE inhib.
Ang Receptor blockers
Isosorbide dinitrate / hydralazine

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23
Q

For diuresis during HF, what 2 types of diuretics are used?

A

Loop diruretics

Spironolactone

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24
Q

For positive ionotropy, what 3 types of drugs are used?

A

Adrenergic agonists
cAMP phosphodiesterase inhibitors
Digitalis glycosides

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25
Q

What are 3 drug classes that are known to reduce mortality when used alone?

A
  • ACEI
  • ARB
  • beta-blockers
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26
Q

What are the 2 major peptides upregulated by ACE inhibitors?

A 
Ang I (Ang 1-7, opposes classical RAS actions)
Bradykinin (potent vasodilator)
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27
Q

What property of ace inhibitors allow them to reduce afterload, Increase stroke volume and cardiac output?

A

More potent dialators or arterial vessels vs. venous vessels

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28
Q

Captopril, enalapril, ramipril, lisinopril, quinapril

and fosinipril are all examples of _

A

ACE inhibitors

29
Q

What is the first line treatment for heart failure / reduced LVEF? What is this usually administered with?

A

ACE inhibitors

Beta blockers

30
Q

Angiotensin receptors mainly block what receptor subtype? What subtype is largely unaffected and what is its effect? What peptide is directly increased by this class of drug?

A

AT1
AT2 - promotes vasodilation and naturesis
Increases Ang II

31
Q

What are 3 angiotensin receptor blockers used in the treatment of heart failure?

A

Losartan
Valsartan
Candesartan

32
Q

Which has better survival in heart failure patients, ACE inhibitors or Angiotensin receptor blockers? What happen to survival when both are combined?

A

Comparable survival rates for both

No additive benefit when both are combined

33
Q

What is the preferred class of diuretics for treatment of heart failure? What class may be used in patients with hypertension?

A

Loop diuretics

THiazides in hypertensive patients

34
Q

What class of drug will provide the fastest relief of symptoms in patients with heart failure?

A

Diuretics

35
Q

How should diuretics be used in treatment of stage C heart failure?

A

Should be used in combination with another agent, shouldn’t be used alone

36
Q

How do diuretics affect survival in heart failure patients?

A

No mortality benefit, address symptoms

37
Q

How are sympatomimetics used in the treatment of heart failure? Why?

A

Used only for short term

Increase mortality in patients

38
Q

What are 3 benefits of beta blockers in heart failure patients?

A

improve symptoms
improve exercise tolerance
increase LVEF

39
Q

What is the effect of phosphorylation of the ryanodine receptor? What drug class is blocks / reduces this phosphorylation?

A

Increased phospho. causes calcium leak from sarcoplasmic reticulum, decreased contractility
Beta blockers

40
Q

What is the effect of beta blockers on cardiac remodeling?

A

Blocks remodeling

41
Q

What types of heart failure patients should get beta blockers? What is the exception?

A

All patients with HF due to LVEF

No beta blockers if contraindicated (reactive airway disease, bradycardia)

42
Q

What are 3 beta blockers used in heart disease and what are their receptor targets?

A

Bisoprolol
Metoprolol - selective beta 1 block
Carvedilol - blocks alpha 1, beta 1 and 2

43
Q

What is the effect of Metoprolol, carvedilol and bisoprolol on mortality?

A

All three reduce mortality

44
Q

What are the 3 cardiac glycosides used in the treatment of heart failure?

A

Digoxin
Digitoxin
Ouabain

45
Q

In addition of heart failure, what is another use for digoxin?

A

Arrythmias

46
Q

What is the mechanism of action of digoxin? What is its receptor target? What are 2 by products of improved contractility following digoxin treatment?

A

Increases contraction force by increasing intracell. calcium.
Sodium/ potassium ATPase
Reduced symp. NS activity, increased renal perfusion

47
Q

How does digoxin reduce the sodium gradient within the cell? What is the main channel affected? How does this affect calcium In the cell?

A

Reduces the gradient
Blocks activity of the sodium calcium exchanger
Increased calcium in cell, increase calcium uptake into sarcoplasmic reticulum, increase calcium release with depolarization, increased contractile force

48
Q

What is the effect of digoxin on cardiac baroreceptors? Why is this significant?

A

It resensitizes these receptors

It leads to decreased sympathetic and increased parasymp input to heart

49
Q

What is the receptor target of digoxin in the kidney? What is the significance?

A

It inhibits the sodium/potasium ATPase

Reduces sodium reabsorption in proximal tubule, leading to increase sodium in distal tubule, decreased renin release

50
Q

What are the glycosides approved for use clinically?

A

Only digoxin

51
Q

Digoxin is no longer a first line treatment for heart failure. What patients may be prescribed digoxin? (2)

A

Heart failure with atrial fibrillation

Patients refrctory to diuretcis, ACE inhib, ang inhib and beta blockers

52
Q

What is the major toxicity associated with digoxin? What use of digoxin predisposes a patient to toxicity? How can toxicity be countered?

A

Arrhythmias, cardiac block
Long term use
Digoxin immunotherapy

53
Q

What is the effect of digoxin on survival? What are risk associated with higher doses of digoxin?

A

No effect on survival

Increased risk of death from MI and arrhythmias

54
Q

What are the 2 examples of aldosterone antagonists provided? What 2 classes of drug must be prescribed with the?

A

Spironolactone and Eplerenone

1) ACE inhib or ang receptor blocker and 2) diuretic

55
Q

What is the effect of aldosterone on the heart?

A

Negative cardiac remodeling effects

56
Q

What would be the effects of venodilators on heart function? (2)

A

Decrease filling pressure

Decrease intracardiac pressure

57
Q

Arteriodilator [increase/decrease] vascular resistance and [increase/decrease] renal perfusion which [promotes / prevents] diuresis

A

Decrease
Increase
Promotes

58
Q

Nitroglycerin, isosorbide dinitrate and isosorbide mononitrate. Among the preceding, which is Short acting? quick acting? Long acting?

A

Short acting - iso dinitrate
Quick - Nitroglycerin
Long - Iso mono-nitrate

59
Q

Isosorbide dinitrate preferentially works on [arteries / veins]. Its major action is to therefore decrease [preload / afterload]. It is usually used in concert with _

A

Veins
Preload
Hydralazine

60
Q

Hydralazine preferentially works on [arteries / veins]. Its major effect is to increase perfusion of _ [organ]. What is the drug that is a combo of isosorbide dinitrate and hydralazine?

A

Arteries
Kidneys
BiDil

61
Q

What is the major drug for use during decompensated heart failure? What are the 2 heart function related parameters it reduces?

A

IV Sodium Nitroprusside

Ventricular filling pressure, systemic vascular resistance

62
Q

To treat acute MI or quickly reduce ventricular filling pressure, what is the drug of choice? What type of vessel is it selective for?

A

IV notroglycerin

Venous capacitance vessels

63
Q

What are 3 parenteral positive ionotropic agents that can be used to treat refractory heart failure patients?

A

Dobutamine
Dopamine
Milrinone

64
Q

With regards to the heart and vasculature, what are the target receptors and effects of dopamine?

A

Beta adrenergic receptors (stimulation) - increased contractility
Alpha adrenergic receptors (stimulation) - increases vascular pressure (good if patient has low BP)

65
Q

What is the receptor target for dobutamine? It is the drug of choice for what cardiac disorders?

A

Beta agonist

Systolic dysfunction and congestion

66
Q

What is the major effect of dobutamine, positive ionotropy or chronotropy? What are the 2 major side effects?

A

Positive ionotropy

Tachycardia and arrhythmias

67
Q

What are 2 cAMP phosphodiesterase inhibitors that can be used to treat advanced heart failure? What is the main ion affected? Where is this ion affected?

A

Inamrinone and Milrinone
Calcium
Increased cytoplasmic calcium

68
Q

Between Inamrinone and Milrinone , which has more favorable side effect profile, shorter half live, and more selective for PDE3?

A

Milrinone

Medical Pharmacology Exam 3 (13 decks)

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