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