Lecture 10: Inotropic Agents and Pharmacology of Heart Failure Flashcards

1
Q

What drug class is Digoxin?

A

Cardiac Glycosides

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2
Q

What are the 3 primary mechanisms by which inotropes (increase heart muscle contractions) affect cardiac muscle?

A
  1. Increasing intracellular Ca2+ (Cardiac Glycosides = Digoxin)
  2. Increasing intracellular cAMP (Symphatomimetics = Dobutamine)
  3. Decreasing breakdown of cAMP (PDE III inhibitors)
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3
Q

Explain calcium-induced calcium release (6)

A
  1. Na influx causes depolarization
  2. After depolarization, calcium flows in
  3. Calcium binds to RyR receptors and causes conformational change releasing calcium from SR
  4. Calcium from SR causes contraction
  5. Na/Ca exchanger removes calcium from the cytosol
  6. Na/K pump releases calcium to maintain gradient
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4
Q

Review slide 6

A

Review slide 6

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5
Q

Pharmacodynamics of Digoxin

How does digoxin affect heart failure (3)?

A
  • Decreases sympathetic tone
  • Decreases plasma norepinephrine
  • Decreases RAAS activity
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6
Q

What are the pharmacodynamics of Digoxin (2)?

A
  • Positive inotropic effect
  • Increases vagal tone (increases sodium in the cell = depolarization = increases vagal tone)

  • Also inhibits Na/K pump in neurons
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7
Q

Digoxin Clinical Use

How does Digoxin treat heart failure?

A
  • inotropic agent
  • helps the heart contract and pump
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8
Q

Digoxin Clinical Use

How does Digoxin treat atrial fibrillation?

A
  • Controls ventricular response rate
  • Prevents ventricular tachy or fib
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9
Q

Digoxin Clinical Use

How does Digoxin treat atrial fibrillation in heart failure?

A

rate control

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10
Q

What are the clinical effects of Digoxin in heart failure (4)?

A
  • Improve symptoms
  • Modest reduction in hospitalization
  • Lower plasma concentrations in the therapeutic range improve survival
  • Higher plasma concentrations in the therapeutic range may increase mortality

Therapeutic range is very low

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11
Q

What are the consequences of cell depolarization by Digoxin (5)?

A
  • Increases vagal activity = increases Na deploarization of vagal neurons
  • Decreases S-A Node Rate
  • Increases Automaticity
  • Increases ectopic beats

Slide 10

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12
Q

Na can _____ so much that it will _____ the antiporter. 3 Na out and 1 Ca in

A
  • increase
  • reverse
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13
Q

Review slide 12

A

Review slide 12

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14
Q

What are the electrical signs of toxicity (3)?

A
  • Loss of plateau
  • RMP becomes more positive
  • Delayed after depolarization
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15
Q

Review slide 13

A

Review slide 13

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16
Q

What are the cardiac adverse reactions of Digoxin (5)?

A
  • Asystole = increases vagal tone
  • Atrial tachycardia
  • AV block
  • Premature ventricular contractions (PVCs)
  • Syncope
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17
Q

What are the non-cardiac (increases parasympathetic) adverse reactions of Digoxin?

A
  • Diarrhea
  • Nausea/Vomiting
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18
Q

What is the therapeutic index for Digoxin?

A

2

Want 10

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19
Q

What are Digoxin contraindications that affect cardiac muscle (2)?

A
  • Ventricular fibrillation (absolute contraindication)
  • Ventricular arrhythmias/tachycardia

Increases cardiac muscle b/c increases excitability of heart

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20
Q

What are Digoxin contraindications that affect the vagus nerve (4)?

A
  • Wolf-Parkinson-White Syndrome
  • AV block
  • Bradycardia
  • Sick sinus syndrome

Increases vagus nerve b/c increases AV node

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21
Q

Digoxin toxicity

What is the treatment for 1st degree heart block and ectopic beats?

A

reduce dose

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22
Q

Digoxin toxicity

What is the treatment for advanced heart block?

A

Atropine

block parasympathetic

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23
Q

Digoxin toxicity

What is the treatment for increased automaticity?

A

KCL

K and digoxin competing for same binding site

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24
Q

Digoxin toxicity

What is the treatment for toxic serum concentration ; acute toxicity?

A

Fab antibodies

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25
What occurs when heart failure progresses (3)?
* Heart damage = blood is not pumping * RAAS/Sympathetic increases * Heart is trying to compensate = causes more damage ## Footnote Slide 18
26
What is the severity of Stage A?
* **High risk **for developing HF * **No structural heart disease **
27
What medical conditions would a patient have in Stage A (4)?
* Hypertension * Coronary artery disease * DM/metabolic syndrome * Family hx of cardiomyopathy
28
What is the severity of Stage B?
* **Structural heart disease ** * **No sx of heart failure** ## Footnote General measures for patients that are asymptomatic
29
What medical conditions would a patient have in Stage B (3)?
* Previous MI * Left ventricle remodeling (LVH and decrease EF) (i.e. reduced ejection fraction, <40% or myocardial injury) * Asymptomatic valvular disease
30
What is the severity of Stage C?
** Structural heart disease w/sx of heart failure** (now or previously)
31
What medical conditions would a patient have in Stage C (3)?
* Known structural heart disease * Shortness of breath * Reduced exercise tolerance
32
What is the severity of Stage D?
* Refractory HF requiring specialized interventions * Not treatable, only option is heart transplant
33
What medical condition would a patient have in Stage D?
**Marked sx at rest despite maximal medical therapy** ## Footnote E.g. recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions
34
What are the classifications of recommendation (4) and level of evidence (4)?
Classification of Recommendation * Class I (Should) = Benefit >>>Risk * Class IIa (Reasonable) = IIa Benefit >> Risk * Class IIb (May be considered) = Benefit ≥ Risk * Class III (Not helpful or harmful) = Risk ≥ Benefit Level of Evidence * A = High quality, multiple RCT * B = Moderate quality, 1 RCT or non RCT * C = Limited data/expert opinion * Z = Lunch
35
In Stage A Therapy, what is a Class I/Level A drug used for?
**Hypertension and lipid disorders** that should be controlled to lower the risk of heart failure ## Footnote Slide 21
36
What is a Class 1/Level C drug used for in Stage A therapy?
Other conditions that may lead to or contribute to HF, such as **obesity, DM, tobacco use, and known cardiotoxic agents ** that should be controlled or avoided
37
Why is Stage A therapy: Class III, Level C not recommended?
**Routine use of nutritional supplements** (Co-Q10, carnitine, taurine, antioxidants, etc.) **solely** to prevent the development of strucutal heart disease should not be recommended for patients at high risk for developing HF.
38
All Class I recommendations for Stage A should apply to patients with what condition?
cardiac structural abnormalities who hav enot developed HF
39
What Stage B Therapy: Class I, Level A drug classes (3) should be used in all patients with a **recent or remote hx of MI regardless of EF or prescence of HF**?
**ACE inhibitors or ARB (alternative to ACE inhibitors) + Beta-blockers** ## Footnote If hx of MI with beta blocker + ACEI/ARB (LOL + Pril/Sartan)
40
What Stage B Therapy: Class I, Level A drug classes (2) should be used patients with a **reduced EF and no sx of HF**, even if they have not experienced MI?
**ACE inhibitor or ARB (alt to ACE inhibitor)** ## Footnote Reduced EF tx with just ACE inhibitor/ARB (Pril/Sartan)
41
What Stage B Therapy: Class I, Level C drug classes (1) are indicated in all patients without a hx of MI who have a **reduced LVEF with no HF symptoms**?
Beta blockers ## Footnote If LV impaired tx with BB (LOL)
42
What medical condition under Stage B Therapy: Class I, Level 1 should be **controlled** in accordance with clinical practice guidelines for HTN to prevent symptomatic HF?
**Blood pressure ** ## Footnote Control BP
43
What drugs classes combinations (2) are used for the initial treatment of HTN in patients with left ventricular hypertrophy?
* Thiazide/thiazide-like + ACE inhibitor * ARB + CCB ## Footnote ACEI cannot be combined with ARB
44
**Beta blockers cause problems for individuals at what age?**
60+
45
Which drugs (2) can increase left ventricular hypertrophy?
**Vasodilators:** * **Hydralazine** * **Minoxidil **
46
**Which 2 drugs is NOT used to treat HTN?**
* **Hydralazine** * **Minoxidil **
47
Which drug in Stage B: Class III, Level C should not be used in patients with low EF, sinus rhythm, and no hx of HF symptoms b/c in this population, **the risk of harm is not balanced by any known benefit**?
Digoxin
48
Which drugs class in Stage B Therapy: Class III, Level C may be harmful in patients with **low LVEF and no symptoms of HF** after MI?
CCB with negative inotropic effects
49
Stage B Therapy: Class III, Level C: Use of ____ ____ to treat structural heart disease or to prevent the development of symptoms of HF is not recommended.
**nutritional supplements **
50
# Stage C Therapy: Class I, Level B Which types of drugs (2) should be avoided or withdrawn whenever possible because they are known to adversely affect patients with current or prior symptoms of HF and reduced LVEF?
* **NSAID (Fluid)** * **Antiarrhythmic drugs**
51
# Stage C: Class I, Level A Which classes of drugs (2) are recommended for patients with **HF*r*EF (heart failure with reduced ejection fraction) and current or prior symptoms, unless contraindicated to reduced morbidity and mortality**?
ACE inhibitors or ARBs
52
# Stage C Therapy: Class I, Level B In patients with chronic symptomatic HF*r*EF who tolerate an _____ or ____, replacement by an _ is recommended to further **reduce morbidity and mortality**
* ACE inhibitor or ARB * ARNI (angiotensin receptor-neprilysin inhibitor)
53
# Stage C Therapy: Class I, Level Addition of which type of receptors (1) are recommended in patients to reduce morbidity and mortality? Why should K+ be monitored?
* **aldosterone receptor anatagonists = Spironolactone** * K+ should be **monitored to minimize the risk of hyperkalemia and renal insufficiency** ## Footnote ACE inhibitor (Pril) or ARB (Sartin) + Spironolactone = decreases remodeling
54
# Stage C Therapy: Class I, Level A Use of 1of the 3 beta blockers proven to reduce mortatlity (i.e. ______, ______, and sustained release _______ ______) is recommended for all stable patients with current or prior **symptoms of HF and reduced LVEF unless contraindicated**.
* **bisoprolol** * **carvedilol** * **metoprolol succinate** ## Footnote ACEI/ARB + ARB + Spiranolactone + BB
55
# Stage C Therapy: Class I, Level B Combining these 2 drugs is recommended to reduce morbidity and mortality for patients self-described as African American with NYHA class III-IV HF*r*EF receiving **optimal therapy with ACE inhibitors and beta blockers** unless contraindicated.
* **Hydralazine** * **Isosorbide** ## Footnote Low renin producers = ACEI or ARB + BB + Hydralazine/Isosorbide dinitrate
56
_____ and ____ are indicated in patients with current or prior symptoms of HF and reduced LVEF who have evidence of **fluid retention**
* Diruetics * sal restriction
57
# Stage C Therapy: Class IIa, Level B Which drug can be** beneficial in patients with HF*r*EF** unless contraindicatioed to decrease hospitizations for HF?
Digoxin
58
# Stage C Therapy: Class IIa, Level B The addition of which 2 drugs is resonable for patients with reduced LVEF who are already taking an ACEI and beta blocker for **symptomatic HF and who have persistent symptoms**?
hydralazine and a nitrate ## Footnote Normal renin = ACEI or ARB + BB + Hydralazine/isosoribide dinitrate (pallative)
59
# Stage C Therapy: Class IIb, Level B Addition of which drug class may be considered in persistently symptomatic pateints with HF*r*EF who are already being treated with an ACE inhibitor and a beta blockers in whom an **aldosterone antagonist is not indicated or tolerated**?
ARB ## Footnote **Exception to ACE-I ARB rule**
60
A combination of what 2 drugs might be resonable in patients with prior symtpos of HF and reduced LVE who **cannot be given ACEI or ARB** because of drug intolerance, hypotension, or renal insufficiency?
hydralazine and a nitrate ## Footnote **Intolerance = exception to ACE-I or ARB rule**
61
# Stage C Therapy: Class III, Level C = Therapies NOT recommended Routine combined use of an ____, ____, and ______ is NOT recommended for patients with current or prior symptoms of HF and reduced LVEF
**ACE-I, ARB, and aldosterone antagonist ** ## Footnote Never ACE-I + ARB + AA
62
# Stage C Therapy: Class III, Level C = Therapies NOT recommended **What class of drugs (1) are not recommended as routine treatment for patients with HF*r*EF?**
**Calcium channel-blocking ** ## Footnote **Amlodipine is the exception for HTN**
63
# Stage C Therapy: Class III, Level C = Therapies NOT recommended Long-term use of an infusion of a positive _____ drug may be harmful and is not recommended for patients with current or prior symptoms of HF and reduced LVEF
inotropic
64
# Stage C Therapy: Class III, Level C = Therapies NOT recommended Inappropriate use of **aldosterone receptor antagonists** is potentially harmful because of ______ or _______ if there is a renal dysfunction and/or elevated plasma potassium
**life-threatening hyperkalemia or renal insufficiency**
65
# Stage D Therapy: Class I, Level B Meticulous identification and control of ____ ____ is recommended in patients with refractory end-stage HF.
fluid retention ## Footnote Controlling fluid overload can increase survival
66
# Stage D Therapy: Class IIa, Level B Continuous intravenous inotropic support is reasonable as "______" in patients with stage D HF refractory to guideline-directed medical therapy (GDMT) and device therapy who are eligible for an awaiting mechanical circulatory support (MCS) or cardiac transplantation
* **bridge therapy** * **DOBUTAMINE**