Module 3.2.2: Drugs Used in Heart Failure Flashcards

1
Q

 Occurs when cardiac output is inadequate to provide oxygen needed by the body.

 It is a progressive disease that is characterize by a gradual reduction in cardiac performance, punctuated in many cases by episodes of acute decompensation

 Most common cause: coronary artery disease.

A

Heart failure

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2
Q

o reduced cardiac output.

o reduced ejection rate fraction (

A

Systolic failure

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3
Q

o A result of hypertrophy and stiffening and loss of adequate relaxation of the myocardium.
o Cardiac output is reduced.
o Ejection fraction may be normal.
o Does not usually respond optimally to positive inotropic drugs.
o Proportion of patients increase with age.
o Stroke volume is significantly decreased.

A

Diastolic failure

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4
Q

o Result from hyperthyroidism, beriberi, anemia, and arteriovenous shunts.
o Treated by correcting the underlying cause.

Manifestations:
o Heart failure tachycardia
o Decreased exercise tolerance
o Shortness of breath
o Peripheral and pulmonary edema
o Cardiomegaly
o Rare form of heart failure.
o Demands of the body are so great that even an increase in cardiac output is insufficient.
A

High-output failure

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5
Q

______ helpful mainly in acute systolic failure and also reduces symptoms in chronic systolic heart failure.

A

Positive inotropic drugs

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6
Q

o A sodium pump and the site of action of cardiac glycosides.
o The major determinant of sodium oncentration in the cell.
o The primary target of Digoxin and other cardiac glycosides.

A

Na+/K+-ATPase

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7
Q

o A sodium-calcium exchanger.
o Uses the sodium gradient to move calcium against its concentration gradient from the cytoplasm to the extra-cellular space.

A

NCX

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8
Q

o A voltage-gated, L-type calcium channel.

A

Cav-L

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9
Q

o A calcium transporter ATPase that pumps calcium into the sarcoplasmic reticulum (SR).
o Maintains free cytoplasmic calcium at very low levels during diastole by pumping calcium into the SR.

A

SERCA (sarcoplasmic endoplasmic reticulum Ca2+ -ATPase)

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10
Q

SERCA is inhibited by _______; phosphorylation of _______ by protein kinase A (eg, by βagonists) removes this inhibition.

A

phospholamban

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11
Q

A calcium bound to calsequestrin, a high-capacity Ca2+-binding protein.

A

CalS

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12
Q

A calcium-activated calcium channel in the membrane of the SR that is triggered to release stored calcium.

A

RyR (ryanodine RyR2 receptor)

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13
Q

Acts at the actin-troponin-tropomyosin complex where activator calcium brings about the contractile interaction of actin and myosin.

A

Calcium sensitizers

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14
Q

_____ increases calcium sensitivity, inhibits phosphodiesterase, and reduces symptoms of heart failure.

A

Levosimedan

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15
Q

Neurohumoral or extrinsic compensation involves two major mechanisms:

A

o Sympathetic Nervous System

o Renin-Angiotensin-Aldosterone Hormonal Response

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16
Q

The most important intrinsic compensatory mechanism is ______.

A

myocardial hypertrophy

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17
Q

the term applied to dilation (other than that due to passive stretch) and other slow structural changes that occur in the stressed myocardium. It may include proliferation of connective tissue cells as well as abnormal myocardial cells with some bio-chemical characteristics of fetal myocytes.

A

Remodeling

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18
Q

o Failure is associated with no limitations on ordinary activities
o Symptomatic only with greater than ordinary activity (severe exercise.

A

HEART FAILURE: Class I

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19
Q

o Slight limitation of ordinary activities

o Fatigue and palpitations with ordinary physical activity.

A

HEART FAILURE: Class II

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20
Q

o Failure results in no symptoms at rest.

o Fatigue, shortness of breath, and tachycardia occur with less than ordinary physical activity.

A

HEART FAILURE: Class III

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21
Q

o Associated with symptoms even when the patient is at rest.

A

HEART FAILURE: Class IV

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22
Q

______ patients are at high risk because of other disease but have no signs or symptoms of heart failure.

Treatment of patients at high risk should be focused on control of hypertension, hyperlipidemia, and diabetes, if present.

A

Stage A

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23
Q

______ patients have evidence of structural heart disease but no symptoms of heart failure.

Treatment of patients at high risk should be focused on control of hypertension, hyperlipidemia, and diabetes, if present.

A

Stage B

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24
Q

______ patients have structural heart disease and symptoms of failure, and symptoms are responsive to ordinary therapy.

Active treatment must be initiated.

A

Stage C

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25
______ patients have heart failure refractory to ordinary therapy, and special interventions (resynchronization therapy, transplant) are required.
Stage D
26
Cardiac performance is a function of four primary factors:
1. Preload 2. Afterload 3. Contractility 4. Heart rate
27
Digitalis that inhibit the Na+/K+-ATPase pump
cardiac glycosides
28
... are steroids proposed to have endogenous digitalis-like properties.
Ouabain or marinobufagenin
29
 Obtained from Digitalis lanata (white foxglove)  MOA: inhibits Na+/K+ ATPase (sodium pump)
Digoxin
30
cardiac glycosides increase contraction of the cardiac sarcomere by increasing the free calcium concentration in the vicinity of the contractile proteins during systole.
Mechanical effects of Digoxin
31
A mixture of direct and autonomic actions. Direct actions on the membranes of cardiac cells follow a well-defined progression: an early, brief prolongation of the action potential, followed by shortening (plateau phase).
Electrical Effects of Digoxin
32
At low dose: | cardiac _______ effects predominate; account for early electrical effects of digitalis.
parasympathomimetic
33
At toxic levels: ______ outflow is increased; sensitizes the myocardium and exaggerates all the toxic effects of the drug.
sympathetic
34
GI tract – most common extra cardiac site of digitalis toxicity, which are ....
Anorexia, nausea, vomiting, and diarrhea
35
______ reduces the enzyme-inhibiting actions of cardiac glycosides, whereas ______ facilitates these actions.
Hyperkalemia | hypokalemia
36
Abnormal automaticity is inhibited by ________: Moderately increased extracellular K+ reduces the effects of digitalis, especially the toxic effects.
hyperkalemia
37
_____ facilitates the toxic actions of cardiac glycosides by accelerating the overloading of intracellular calcium stores.
Ca2+
38
______ increases the risk of a digitalis induced arrhythmia.
Hypercalcemia
39
In severe intoxication, serum K+ is already elevated, automaticity is depressed, and anti-arrhythmic agents administered in this setting may lead to cardiac arrest.
Digoxin Toxicity
40
Digoxin Toxicity Treatment: prompt insertion of a ______ and administration of _________ (digoxin immune fab)
pacemaker | digitalis antibodies
41
... is an investigational steroid derivative that increases contractility by inhibiting Na+/K+ -ATPase (like cardiac glycosides) but in addition facilitates sequestration of Ca2+ by the SR.
Istaroxime
42
MOA:  inhibit phosphodiesterases  Inhibition of phosphodiesterase increases cAMP and increases contractility and vasodilation.  increase myocardial contractility by increasing inward calcium flux in the heart during the action potential.  Although they have positive inotropic effects, most of their benefits derive from vasodilation
Bipyridines
43
– used only intravenously and only for acute heart failure or severe exacerbation of chronic heart failure.
Inamrinone and Milrinone
44
Inamrinone toxic effects include:
o nausea and vomiting o arrhythmias o thrombocytopenia o liver enzyme changes
45
______ appears less likely to cause bone marrow and liver toxicity
Milrinone
46
(selective β1 agonist), a parenteral drug
Dobutamine
47
 It increases cardiac output with a decrease in ventricular filling pressure.  Tachycardia may occur use with caution in patients with CAD or arrhythmia.  Tachyphylaxis may be seen
β-Stimulants/ Beta-adrenoceptor Agonists
48
– also used in acute heart failure and may be particularly helpful if there is a need to raise blood pressure.
Dopamine
49
 Have no direct effect on cardiac contractility.  Reduces venous pressure and ventricular preload >> Reduction of edema and cardiac size >> Improvement of pump efficiency.
Diuretics
50
Aldosterone antagonists that decrease morbidity and mortality in patients with severe heart failure.
Spironolactone and Eplerenone,
51
These drugs reduce the long-term remodeling of the heart and vessels, an effect that may be responsible for the observed reduction in mortality and morbidity.
ACE inhibitors and ARBs
52
In cases of patients intolerant of ACE inhibitors due to incessant cough, add ______ (an Angiotensin receptor blocker) with the ACE inhibitor to have beneficial effects.
candesartan
53
______ a renin inhibitor, appears to have efficacy similar to that of ACE inhibitors.
Aliskiren
54
 Effective in acute heart failure.  Reduce preload (venodilation), or afterload (arteriolar dilation), or both.  Most common adverse effect: Excessive hypotension.
Vasodilators
55
Long-term use of these vasodilators can also reduce damaging remodeling of the heart.
Hydralazine and Isosorbide dinitrate
56
inhibitors of endothelin, approved in pulmonary hypotension.
Bosentan and Tezosentan
57
...has significant teratogenic and hepatotoxic effects.
Bosentan
58
______, approved for use in acute cardiac failure, increases cGMP in smooth muscle cells and reduces venous and arteriolar tone in experimental preparations. It also causes diuresis.
Nesiritide
59
MOA: o Attenuation of the adverse effects of high concentrations of catecholamines (including apoptosis) o Up-regulation of β-receptors o Decreased heart rate o Reduced remodeling through inhibition of the mitogenic activity of catecholamines
β-Blockes/ Beta-adrenoceptor blockers
60
first-line therapy for heart failure
Diuretics
61
______ is reserved for patients who do not respond adequately to diuretics, ace inhibitors and β-blockers.
Digitalis
62
Give ______ if systolic dysfunction with 3rd heart sound or atrial fibrillation is present.
digitalis
63
Give ______ to patients with stable class II-IV heart failure.
β-blockers
64
In mild failure, start with a ______, switching to ______ as required.
Thiazide diuretic | Furosemide
65
.... should be considered in all patients with moderate or severe heart failure.
Spironolactone or eplerenone
66
______ should be monitored in patients receiving any of these HF drugs
Serum potassium
67
 In patients with left ventricular dysfunction but no edema, ______ should be used first.  ______ are superior to vasodilators and must be considered, along with diuretics, as first-line therapy for chronic failure.  ______ are nonselective arteriolar and venous dilators.
ACE inhibitors
68
....should only be used in patients who are intolerant of ACE inhibitors (usually because of cough).
ARBs (losartan, candesartan)
69
... is useful in atrial arrhythmias due to its cardioselective parasympathomimetic effects
Digitalis
70
Contraindicated in patients with Wolff-Parkinson-White syndrome and atrial fibrillation. (increases the conduction of atrial arrhythmia through the aberrant pathway)
Digitalis
71
A common cause of acute failure is ....
MI
72
Acute MI patients can be characterized on the basis of three hemodynamic measurements:
arterial pressure, left ventricular filling pressure, and cardiac index.
73
A new V1a and V2 receptor antagonist, ______, has recently been approved for the parenteral treatment of euvomic hyponatremia.
conivaptan
74
Studies suggest that ______ is effective in both systolic and diastolic failure.
Nebivolol
75
MOA: Loop diuretic: Decreases NaCl and KCl reabsorption in thick ascending limb of the loop of Henle in the nephron
Furosemide
76
EFFECTS: * Increased excretion of salt and water * reduces cardiac preload and afterload * reduces pulmonary and peripheral edema
Furosemide
77
TOXICITY: Hypovolemia, hypokalemia, orthostatic hypotension, ototoxicity, sulfonamide allergy
Furosemide
78
MOA: Decreases NaCl reabsorption in the distal convoluted tubule
Hydrochlorothiazide
79
EFFECTS: Same as furosemide, but less efficacious
Hydrochlorothiazide
80
TOXICITY: Hyponatremia, hypokalemia, hyperglycemia, hyperuricemia, hyperlipidemia, sulfonamide allergy
Hydrochlorothiazide
81
Similar to spironolactone; more selective antialdosterone effect; no significant antiandrogen action
Eplerenone
82
MOA: • Block cytoplasmic aldosterone receptors in collecting tubules of nephron • possible membrane effect
Spironolactone
83
EFFECTS: * Increased salt and water excretion * reduces remodeling * reduces mortality
Spironolactone
84
TOXICITY: Hyperkalemia, antiandrogen actions
Spironolactone
85
MOA: * Inhibits ACE * reduces AII formation by inhibiting conversion of AI to All
Angiotensin-converting enzyme (ACE) inhibitors: | • Captopril
86
EFFECTS: * Arteriolar and venous dilation * reduces aldosterone secretion * increases cardiac output * reduces cardiac remodeling
Angiotensin-converting enzyme (ACE) inhibitors: | • Captopril
87
TOXICITY: Cough, hyperkalemia, angioneurotic edema
Angiotensin-converting enzyme (ACE) inhibitors: | • Captopril
88
MOA: Antagonize AII effects at AT1 receptors
Angiotensin receptor blockers (ARBs): • Losartan
89
TOXICITY: Hyperkalemia; angioneurotic edema
Angiotensin receptor blockers (ARBs): • Losartan
90
Select group of Beta blockers that reduce heart failure mortality
Metoprolol, bisoprolol
91
Competitively blocks Beta1 receptors
BETA BLOCKERS | • Carvedilol
92
EFFECTS: * Slows heart rate * reduces blood pressure * poorly understood effects * reduces heart failure mortality
BETA BLOCKERS | • Carvedilol
93
TOXICITY: Bronchospasm, bradycardia, atrioventricular block, acute cardiac decompensation
BETA BLOCKERS | • Carvedilol
94
MOA: Na+,K+ ATPase inhibition results in reduced Ca2+ expulsion and increased Ca2+ stored in sarcoplasmic reticulum
CARDIAC GLYCOSIDE | • Digoxin
95
EFFECTS: * Increases cardiac contractility * cardiac parasympathomimetic effect (slowed sinus heart rate, slowed atrioventricular conduction)
CARDIAC GLYCOSIDE | • Digoxin
96
TOXICITY: * Nausea, vomiting, diarrhea * cardiac arrhythmias
CARDIAC GLYCOSIDE | • Digoxin
97
MOA: * Releases nitric oxide (NO) * activates guanylyl cyclase
Venodilators: | • Isosorbide dinitrate
98
EFFECTS: * Venodilation * reduces preload and ventricular stretch
Venodilators: | • Isosorbide dinitrate
99
TOXICITY: Postural hypotension, tachycardia, headache
Venodilators: | • Isosorbide dinitrate
100
MOA: Probably increases NO synthesis in endothelium
Arteriolar dilators: | • Hydralazine
101
EFFECTS: * Reduces blood pressure and afterload * results in increased cardiac output
Arteriolar dilators: | • Hydralazine
102
TOXICITY: Tachycardia, fluid retention, lupus-like syndrome
Arteriolar dilators: | • Hydralazine
103
MOA: * Releases NO spontaneously * activates guanylyl cyclase
Combined arteriolar and venodilator: | • Nitroprusside
104
EFFECTS: * Marked vasodilation * reduces preload and afterload
Combined arteriolar and venodilator: | • Nitroprusside
105
TOXICITY: Excessive hypotension, thiocyanate and cyanide toxicity
Combined arteriolar and venodilator: | • Nitroprusside
106
MOA: * Beta1–selective agonist * increases cAMP synthesis
Dobutamine
107
EFFFECT: Increases cardiac contractility, output
Dobutamine
108
TOXICITY: Arrhythmias
Dobutamine and Dopamine
109
MOA: higher doses activate Beta and Alpha adrenoceptors
Dopamine
110
EFFECTS: * Increases renal blood flow * higher doses increase cardiac force and blood pressure
Dopamine
111
MOA: * Phosphodiesterase type 3 inhibitors * decrease cAMP breakdown
BIPYRIDINES | • Inamrinone, milrinone
112
EFFECTS: * Vasodilators lower peripheral vascular resistance * also increase cardiac contractility TOXICITY: Arrhythmias
BIPYRIDINES | • Inamrinone, milrinone
113
MOA: Activates BNP receptors, increases cGMP
NATRIURETIC PEPTIDE | • Nesiritide
114
EFFECTS: * Vasodilation * diuresis
NATRIURETIC PEPTIDE | • Nesiritide
115
TOXICITY: Renal damage, hypotension
NATRIURETIC PEPTIDE | • Nesiritide