Positive Inotropes - Quiz 3 Flashcards
What are the CV Effects of Septic Shock?
CI
SVR
PAWP(PCWP)
↑Cardiac Index
↓SVR
↓PCWP
What are the CV Effects of Hypovolemic Shock?
CI
SVR
PAWP(PCWP)
↓Cardiac Index
↑SVR
↓PCWP
What are the CV Effects of Cardiogenic Shock?
CI
SVR
PAWP(PCWP)
↓Cardiac Index
↑SVR
↑PCWP
What happens to Intracellular cAMP w/ CHF?
Decreased cAMP
Beta Receptor Downregulation & Impaired Coupling
What does CHF respond to?
Preload Reduction
Afterload Reduction
Improved Contraction
What happens w/ Low Cardiac Output Syndrome after coming off Cardio-Pulmonary Bypass?
Inadequate O2 Delivery
Hemodilution
Hypocalcemia
Hypomagnesemia
Kaliuresis
Tissue Thermal Gradients
Variable SVR
What risk factors contribute to Low Cardiac Output Syndrome (LCOS)?
DM
> 65 y.o.
Female
Decreased LVEF
Prolonged Cardio-Pulmonary Bypass > 6hrs
What is the pathophysiology of LCOS?
- Stunned myocardium (hypo-contractile myocardium in response to ischemia and reperfusion)
- Beta receptor down-regulation has been reported
What is the treatment of LCOS?
- Positive inotropes to increase the contractility of normal and stunned myocardium
- Hypotension, unlike CHF, responds poorly to vasodilators alone.
What might Hypotension in the setting of LCOS NOT respond to?
Vasodilators Alone
What is the Goal when treating LCOS?
- Increase levels of O2 delivery (keep SvO2 >70%)
- Increase O2 consumption (arterial blood lactate level < 2 mmol/L).
What causes Low Cardiac Output Syndrome?
Stunned Heart in response to Ischemia & Reperfusion
&
Beta Receptor Downregulation
Positive Inotropes Hemodynamic effects
Increased contractility with:
Increased Stroke Volume (SV)
Reduced LVEDP and Volume
Hemodynamic effects of ‘’Pure” Beta-1 agonists
(dobutamine/isoproterenol)(Inodilators)
↑ HR
↑ A-V conduction
↓ SVR and PVR (Beta 2 effect)
Variable effect on myocardial consumption
What classes of Positive Inotropes are cAMP Dependent?
Beta Agonist
Dopaminergic Agonists
PDE Inhibitors
What classes of Positive Inotropes are cAMP Independent?
Cardiac Glycosides
&
Calcium
What is Levosimendan used for and how does it work?
LCOS Treatment & Prophylaxis - Calcium Sensitizer to existing calcium in the body
What do Pure Beta-1 Agonists (Inodilators), like Dobutamine & Isoproterenol do?
↑HR
↑A-V Conduction
↓SVR & PVR (Beta-2)
Variable O2 Myocardial Consumption Effects
What do Mixed Alpha/Beta Agonists like NE, Epi, & Dopamine (Inoconstrictors) do?
↑HR
↑SVR
↑Myocardial O2 Consumption
What are complications from using Postive Inotropes?
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
What are the problems w/ using Digoxin?
Narrow Therapeutic Index
Renal Failure
Bradycardia
Drug Interations
Caution w/ Hypokalemia
Which med has the most risk of causing Arrhythmias from most to least?
Isoproterneol > Epi > Dopamine > Dobutamine
What are the cAMP dependent positive inotropes?
cAMP Dependent:
Beta Agonists
Dopaminergic Agonists
Phosphodiesterase Inhibitors
What are the cAMP-independent positive inotropes?
cAMP Independent:
Cardiac Glycosides
Calcium
What do cAMP Dependent Inotropes do?
↑Calcium Influx
↑Calcium Sensitivity
↑Contraction
↑Relaxation
cAMP Dependent Positive Inotropes pharmcokinetics
- 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.
What do low doses (1-2 mcg/min) of Epinephrine do?
Beta 2 Stimulation - > Vasodilate to ↓SVR, but MAP stays the same
Essentially a Vasodilator
What do Intermediate doses (4 mcg/min) of Epinephrine do?
Beta-1 Stimulation - Inotrope
↑HR
↑Contractility
↑Cardiac Output
↑Automaticity
What do High Doses (> 10 mcg/min) of Epinephrine do?
Alpha 1 Stimlulation
Potent Vasoconstriction –> Reflex Bradycardia
Acts as Vasoconstrictor
Which receptors does Norepi act on?
ALPHA 1 > Beta 1
Minimal Beta 2
How does Norepi affect Cardiac Output at Low Doses?
↑Cardiac output
How does Norepi affect Cardiac Output at high doses?
At higher doses CO may decrease due to :
↑Afterload
&
baroreceptor mediated Reflex Bradycardia
Summary of Norepi
- 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
Catecholamine Complications
- 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
Which receptors does Isoproteronal act on?
Beta 1 & Beta 2
What does Isoproterenol do?
↑CO, HR, Contractility, and Automaticity
↓SVR & DBP
Bronchodilation
Net effect is increased C.O. and decreased M.A.P.
When should Isoproterenol be avoided?
In Cardiogenic Shock & Ischemic Heart Disease
When is Isoproterenol used?
S/P Heart Transplant
Complete Heart Block
Bronchospasms
Pulm. HTN
RV Failure
What are the Off-Label uses for Isoproterenol?
Torsades
Ventricular Arrhythmias
Short QT Syndrome
What class of drug is Dobutamine?
Synthetic Catecholamine that acts primarily on BETA 1 Receptors w/
Very Little Beta 2 & Alpha 1 effects
What does Dobutamine do?
Dose Dependent ↑CO & ↑HR
↓Fillling Pressures
Dilate Coronary Vessels
NO Dopamine Receptor effects
What dose of Dobutamine would cause Tachycardia & Dysrrhythmias?
> 10 mcg/kg/min
Why should Dobutamine & Dopamine be mixed in D5W instead of NS?
NS Inactivates these meds
What happens with D1 & D5 Receptor stimulation?
Stimulates Adenylate Cyclase & cAMP
Vasodilation
Naturesis
Diuresis
What happens w/ D2, D3, & D4 Receptor stimulation?
Inhibits Adenylate Clases & cAMP
Inhibit Norepi Release
Vasodilation
↑Renal Blood Flow
What does Low Dose (1-3 mcg/kg/min) Dopamine do?
Renal Dose - D1 & D2 effects
Inhibits Aldosterone
NOT RENAL PROTECTIVE
What does a 3-10 mcg/kg/min dose of Dopamine do?
Beta Effect
↑Contractility & CO WITHOUT HR & BP Changes
Indirectly Releases Norepi
What does a 10-20 mcg/kg/min dose of Dopamine do?
Alpha > Beta Effects
(Alpha starts to take over)
Which receptor is effected with Dopamine doses > 20 mcg/kg/min?
Alpha
How does Dopamine affect Ventilation during Hypoxia?
↓Ventilatory Response d/t Carotid Body Inhibition
How does Dopamine affect Blood Sugar?
Hyperglycemia
What are some side effects of Dopamine?
N/V
Angina
Headache
Tachyarrhythmias
HTN
Which receptor does Fenoldopam act on?
Mostly D1
Some Alpha 2
What are the effects of Fenoldopam?
↓SVR
↑Renal Blood Flow
(NOT Renal Protective)
Reflex Tachy
How does Fenoldopam compare with Sodium Nitroprusside?
Same Effectiveness for BP Control, but also ↑RBF
How does Fenoldopam compare w/ Dopamine?
10-100x more potent
How should Fenoldopam be adminstered?
Slow Titration
No Bolus
What are the side effects of Fenoldopam?
Headache
Flushing
Restless Legs
N/V
T-Wave Inversion
What do PDE3 Inhibitors like Milrinone & Inamrinone do?
↓cAMP breakdown = ↑Calcium & ↑Calcium Sensitivity
↑Cardiac Output
Vasodilation
How does Inamrinone compare to Dobutamine?
More Effective & Less Complications
How does Inamrinone compare to Epi?
Same Effectiveness, but even more if added to Epi
When should Inamrinone be avoided?
Thrombocytopenia
Elevated LFTs
Arrhythmias
Aortic Stenosis
How does Milrinone compare to Inamrinone?
15-20x more potent
Shorter Half-Life
No Thrombocytopenia risk
What are the side effects of Milrinone?
Hypotension
Syncope
Arrhythmias
V-Tach w/ AFib/Flutter
Which receptor does Glucagon work on?
Increases cAMP via Glucagon Receptor, NOT Beta
What are the CV effects of Glucagon?
↑CI
↑HR
↑BP
↓SVR
↓LVEDP
What are the side effects of Glucagon?
↑Blood Sugar
↑Coronary & Pulmonary Vascular Resistance
How do Anticholinergic Meds affect Glucagon?
Enhances the GI Side Effects (N/V)
How does Glucagon affect clotting times?
Vitamin K Antagonist –> Increases INR
What is Digoxin?
A Cardiac Glycoside w/ the effects of
Positive Inotrope
&
Negative Dromotrope & Chronotrope
How does Dixogin work?
Inhibits Na/K-ATPase Pump & causes Calcium to remain in the Myocyte
When is Digoxin used?
Heart Failure
&
A-Fib
What is the Therapeutic Range of Digoxin?
0.8 - 2 ng/mL
What conditions increases the risks of Digoxin Toxicity?
Hypokalemia
Hypomagnesemia
Hypoxemia
Hypothyroid
Hypercalcemia
How does Digoxin Toxicity present?
Anorexia
N/V
Paroxysmal Atrial Tach w/ Block
Mobitz II Block
V-Fib
What is the Antidote for Digoxin Toxicity?
Digibind - Antibody Fragments that bind to drug and decrease Digoxin levels via Kidneys
What is the Strategy for treating Low Cardiac Output?
- Optimize Preload - Venous Dilators, Fluids
- Optimize Afterload - Arterial Dilators, then Inodilator
- Add Inotrope
- IABP or LVAD