Positive Inotropes - Quiz 3 Flashcards

1
Q

What are the CV Effects of Septic Shock?

CI

SVR

PAWP(PCWP)

A

↑Cardiac Index

↓SVR

↓PCWP

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2
Q

What are the CV Effects of Hypovolemic Shock?

CI

SVR

PAWP(PCWP)

A

↓Cardiac Index

↑SVR

↓PCWP

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3
Q

What are the CV Effects of Cardiogenic Shock?

CI

SVR

PAWP(PCWP)

A

↓Cardiac Index

↑SVR

↑PCWP

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4
Q

What happens to Intracellular cAMP w/ CHF?

A

Decreased cAMP

Beta Receptor Downregulation & Impaired Coupling

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5
Q

What does CHF respond to?

A

Preload Reduction

Afterload Reduction

Improved Contraction

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6
Q

What happens w/ Low Cardiac Output Syndrome after coming off Cardio-Pulmonary Bypass?

A

Inadequate O2 Delivery

Hemodilution

Hypocalcemia

Hypomagnesemia

Kaliuresis

Tissue Thermal Gradients

Variable SVR

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7
Q

What risk factors contribute to Low Cardiac Output Syndrome (LCOS)?

A

DM

> 65 y.o.

Female

Decreased LVEF

Prolonged Cardio-Pulmonary Bypass > 6hrs

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8
Q

What is the pathophysiology of LCOS?

A
  • Stunned myocardium (hypo-contractile myocardium in response to ischemia and reperfusion)
  • Beta receptor down-regulation has been reported
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9
Q

What is the treatment of LCOS?

A
  • Positive inotropes to increase the contractility of normal and stunned myocardium
  • Hypotension, unlike CHF, responds poorly to vasodilators alone.
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10
Q

What might Hypotension in the setting of LCOS NOT respond to?

A

Vasodilators Alone

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11
Q

What is the Goal when treating LCOS?

A
  • Increase levels of O2 delivery (keep SvO2 >70%)
  • Increase O2 consumption (arterial blood lactate level < 2 mmol/L).
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12
Q

What causes Low Cardiac Output Syndrome?

A

Stunned Heart in response to Ischemia & Reperfusion

&

Beta Receptor Downregulation

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13
Q

Positive Inotropes Hemodynamic effects

A

Increased contractility with:

Increased Stroke Volume (SV)

Reduced LVEDP and Volume

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14
Q

Hemodynamic effects of ‘’Pure” Beta-1 agonists

(dobutamine/isoproterenol)(Inodilators)

A

↑ HR

↑ A-V conduction

↓ SVR and PVR (Beta 2 effect)

Variable effect on myocardial consumption

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15
Q

What classes of Positive Inotropes are cAMP Dependent?

A

Beta Agonist

Dopaminergic Agonists

PDE Inhibitors

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16
Q

What classes of Positive Inotropes are cAMP Independent?

A

Cardiac Glycosides

&

Calcium

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17
Q

What is Levosimendan used for and how does it work?

A

LCOS Treatment & Prophylaxis - Calcium Sensitizer to existing calcium in the body

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18
Q

What do Pure Beta-1 Agonists (Inodilators), like Dobutamine & Isoproterenol do?

A

↑HR

↑A-V Conduction

↓SVR & PVR (Beta-2)

Variable O2 Myocardial Consumption Effects

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19
Q

What do Mixed Alpha/Beta Agonists like NE, Epi, & Dopamine (Inoconstrictors) do?

A

↑HR

↑SVR

↑Myocardial O2 Consumption

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20
Q

What are complications from using Postive Inotropes?

A

Prolonged High Doses of NE and Epi = Reduced Perfusion

High doses of NE and Epi for prolonged periods with persistent low CO will decrease perfusion to many tissue beds and contribute to renal failure

Isoproterenol (DA, and dobutamine) will worsen Tachyarrhythmias

Digoxin should be used cautiously in patients with hypokalemia, renal failure, bradycardia, drug interactions

Arrhythmogenic potential:

Dobutamine

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21
Q

What are the problems w/ using Digoxin?

A

Narrow Therapeutic Index

Renal Failure

Bradycardia

Drug Interations

Caution w/ Hypokalemia

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22
Q

Which med has the most risk of causing Arrhythmias from most to least?

A

Isoproterneol > Epi > Dopamine > Dobutamine

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23
Q

What are the cAMP dependent positive inotropes?

A

cAMP Dependent:

Beta Agonists

Dopaminergic Agonists

Phosphodiesterase Inhibitors

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24
Q

What are the cAMP-independent positive inotropes?

A

cAMP Independent:

Cardiac Glycosides

Calcium

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25
Q

What do cAMP Dependent Inotropes do?

A

↑Calcium Influx

↑Calcium Sensitivity

↑Contraction

↑Relaxation

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26
Q

cAMP Dependent Positive Inotropes pharmcokinetics

A
  • Catecholamines bind to beta receptors and activate a membrane-bound guanine nucleotide-binding protein
  • This activates adenyl cyclase and generates cAMP.
  • cAMP:

increases Ca influx via slow channels

increases Ca sensitivity of Ca-regulatory proteins.

  • Increase the force of contraction and velocity of relaxation.
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27
Q

What do low doses (1-2 mcg/min) of Epinephrine do?

A

Beta 2 Stimulation - > Vasodilate to ↓SVR, but MAP stays the same

Essentially a Vasodilator

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28
Q

What do Intermediate doses (4 mcg/min) of Epinephrine do?

A

Beta-1 Stimulation - Inotrope

↑HR

↑Contractility

↑Cardiac Output

↑Automaticity

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29
Q

What do High Doses (> 10 mcg/min) of Epinephrine do?

A

Alpha 1 Stimlulation

Potent Vasoconstriction –> Reflex Bradycardia

Acts as Vasoconstrictor

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30
Q

Which receptors does Norepi act on?

A

ALPHA 1 > Beta 1

Minimal Beta 2

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31
Q

How does Norepi affect Cardiac Output at Low Doses?

A

↑Cardiac output

32
Q

How does Norepi affect Cardiac Output at high doses?

A

At higher doses CO may decrease due to :

↑Afterload

&

baroreceptor mediated Reflex Bradycardia

33
Q

Summary of Norepi

A
  • Binds to Alpha-1, Alpha-2 and Beta-1 receptors more readily than Beta-2
  • For a comparable increase in MAP, Epi produces a significantly greater CO compared to NE
  • Has been used as a relative Beta-1 agonist when combined with phentolamine to counteract its potent Alpha-1 and Alpha-2 agonist activity
  • Used as a vasoconstrictor to counter the vasoplegic syndrome that can follow CPB
34
Q

Catecholamine Complications

A
  • Local tissue ischemia from SQ infiltration of inoconstrictors
  • Increased myocardial oxygen consumption
  • Enhance lipolysis and gluconeogenesis
  • Alter electrolyte concentrations
  • Activate coagulation
  • Override microvascular control mechanisms
  • Alter distribution of CO
  • Increase myocardial work
  • Increase the risk of cardiac arrhythmias
35
Q

Which receptors does Isoproteronal act on?

A

Beta 1 & Beta 2

36
Q

What does Isoproterenol do?

A

↑CO, HR, Contractility, and Automaticity

↓SVR & DBP

Bronchodilation

Net effect is increased C.O. and decreased M.A.P.

37
Q

When should Isoproterenol be avoided?

A

In Cardiogenic Shock & Ischemic Heart Disease

38
Q

When is Isoproterenol used?

A

S/P Heart Transplant

Complete Heart Block

Bronchospasms

Pulm. HTN

RV Failure

39
Q

What are the Off-Label uses for Isoproterenol?

A

Torsades

Ventricular Arrhythmias

Short QT Syndrome

40
Q

What class of drug is Dobutamine?

A

Synthetic Catecholamine that acts primarily on BETA 1 Receptors w/

Very Little Beta 2 & Alpha 1 effects

41
Q

What does Dobutamine do?

A

Dose Dependent ↑CO & ↑HR

↓Fillling Pressures

Dilate Coronary Vessels

NO Dopamine Receptor effects

42
Q

What dose of Dobutamine would cause Tachycardia & Dysrrhythmias?

A

> 10 mcg/kg/min

43
Q

Why should Dobutamine & Dopamine be mixed in D5W instead of NS?

A

NS Inactivates these meds

44
Q

What happens with D1 & D5 Receptor stimulation?

A

Stimulates Adenylate Cyclase & cAMP

Vasodilation

Naturesis

Diuresis

45
Q

What happens w/ D2, D3, & D4 Receptor stimulation?

A

Inhibits Adenylate Clases & cAMP

Inhibit Norepi Release

Vasodilation

↑Renal Blood Flow

46
Q

What does Low Dose (1-3 mcg/kg/min) Dopamine do?

A

Renal Dose - D1 & D2 effects

Inhibits Aldosterone

NOT RENAL PROTECTIVE

47
Q

What does a 3-10 mcg/kg/min dose of Dopamine do?

A

Beta Effect

↑Contractility & CO WITHOUT HR & BP Changes

Indirectly Releases Norepi

48
Q

What does a 10-20 mcg/kg/min dose of Dopamine do?

A

Alpha > Beta Effects

(Alpha starts to take over)

49
Q

Which receptor is effected with Dopamine doses > 20 mcg/kg/min?

A

Alpha

50
Q

How does Dopamine affect Ventilation during Hypoxia?

A

↓Ventilatory Response d/t Carotid Body Inhibition

51
Q

How does Dopamine affect Blood Sugar?

A

Hyperglycemia

52
Q

What are some side effects of Dopamine?

A

N/V

Angina

Headache

Tachyarrhythmias

HTN

53
Q

Which receptor does Fenoldopam act on?

A

Mostly D1

Some Alpha 2

54
Q

What are the effects of Fenoldopam?

A

↓SVR

↑Renal Blood Flow
(NOT Renal Protective)

Reflex Tachy

55
Q

How does Fenoldopam compare with Sodium Nitroprusside?

A

Same Effectiveness for BP Control, but also ↑RBF

56
Q

How does Fenoldopam compare w/ Dopamine?

A

10-100x more potent

57
Q

How should Fenoldopam be adminstered?

A

Slow Titration

No Bolus

58
Q

What are the side effects of Fenoldopam?

A

Headache

Flushing

Restless Legs

N/V

T-Wave Inversion

59
Q

What do PDE3 Inhibitors like Milrinone & Inamrinone do?

A

↓cAMP breakdown = ↑Calcium & ↑Calcium Sensitivity

↑Cardiac Output

Vasodilation

60
Q

How does Inamrinone compare to Dobutamine?

A

More Effective & Less Complications

61
Q

How does Inamrinone compare to Epi?

A

Same Effectiveness, but even more if added to Epi

62
Q

When should Inamrinone be avoided?

A

Thrombocytopenia

Elevated LFTs

Arrhythmias

Aortic Stenosis

63
Q

How does Milrinone compare to Inamrinone?

A

15-20x more potent

Shorter Half-Life

No Thrombocytopenia risk

64
Q

What are the side effects of Milrinone?

A

Hypotension

Syncope

Arrhythmias

V-Tach w/ AFib/Flutter

65
Q

Which receptor does Glucagon work on?

A

Increases cAMP via Glucagon Receptor, NOT Beta

66
Q

What are the CV effects of Glucagon?

A

↑CI

↑HR

↑BP

↓SVR

↓LVEDP

67
Q

What are the side effects of Glucagon?

A

↑Blood Sugar

↑Coronary & Pulmonary Vascular Resistance

68
Q

How do Anticholinergic Meds affect Glucagon?

A

Enhances the GI Side Effects (N/V)

69
Q

How does Glucagon affect clotting times?

A

Vitamin K Antagonist –> Increases INR

70
Q

What is Digoxin?

A

A Cardiac Glycoside w/ the effects of

Positive Inotrope

&

Negative Dromotrope & Chronotrope

71
Q

How does Dixogin work?

A

Inhibits Na/K-ATPase Pump & causes Calcium to remain in the Myocyte

72
Q

When is Digoxin used?

A

Heart Failure

&

A-Fib

73
Q

What is the Therapeutic Range of Digoxin?

A

0.8 - 2 ng/mL

74
Q

What conditions increases the risks of Digoxin Toxicity?

A

Hypokalemia

Hypomagnesemia

Hypoxemia

Hypothyroid

Hypercalcemia

75
Q

How does Digoxin Toxicity present?

A

Anorexia

N/V

Paroxysmal Atrial Tach w/ Block

Mobitz II Block

V-Fib

76
Q

What is the Antidote for Digoxin Toxicity?

A

Digibind - Antibody Fragments that bind to drug and decrease Digoxin levels via Kidneys

77
Q

What is the Strategy for treating Low Cardiac Output?

A
  1. Optimize Preload - Venous Dilators, Fluids
  2. Optimize Afterload - Arterial Dilators, then Inodilator
  3. Add Inotrope
  4. IABP or LVAD