Inotropes & Beta Blockers in Congestive HF Flashcards
What are the four factors that determine cardiac output?
Heart rate
Contractility
Preload
Afterload
What are the two major compensatory mechanisms in systolic heart failure?
Activation of RAAS
Sympathetic system activation
What occurs when RAAS is activated as a compensatory mechanism in systolic heart failure?
Decreased renal perfusion pressure due to heart failure activates RAAS
Angiotensin II –> vasoconstriction –> increased afterload
Aldosterone –> Na+/water retention –> edema
What occurs when sympathetic system is activated as a compensatory mechanism in systolic heart failure?
Sympathetic activation increases plasma NE
Increases HR
Increases contractility
What are the long term effects of sympathetic stimulation in heart failure?
Maladaptive proliferation (hypertrophy, fibrosis) Myocyte apoptosis Worsening LV dysfunction and HF symptoms
Which beta blockers have been documented to have a survival benefit in HF?
Metoprolol
Bisoprolol
Carvedilol
What are the acute effects of beta blockers in HF?
Decrease contractility (attenuated adenylyl cyclase, PKA) Negative chronotropy (reduced SA activity, slowed conduction in AV, increased refractory period in AV)
Overall, acutely causes further decrease in CO
What occurs on Day 1 of beta blocker use?
Significant decrease in ejection fraction
Must make sure patient can tolerate this
What are the long term effects of beta blockers in HF?
Improved survival
Improved LV ejection fraction
Decrease in sudden death events
What is the mechanism for the improved survival in HF with use of beta blockers?
Unknown! Maybe just protecting heart from sympathetic overstimulation
What are guidelines for beta blocker use in systolic dysfunction HF?
Initiate beta blockers at low dose, then increase slowly
Class III and IV patients approached with caution
Patients with new onset should only be treated once stabilized
When should inotropes be used as opposed to beta blockers?
Beta blockers - patient is stable, need to chronically manipulate receptors, short term pain for long term good
Inotropes - patient is decompensated, need to acutely manipulate receptors
What catecholamines are used as inotropes?
Dobutamine
Dopamine
What phosphodiesterase Type 3 inhibitors are used as inotropes?
Milrinone
How do catecholamines result in greater force of contraction?
NE, Epi stimulate Beta receptor, increase cAMP, activate PKA
PKA
Phosphorylates Ca channel, more Ca in cell
Phosphorylates phospholamban, more uptake of Ca into SR
Phosphorylates Troponin, enhanced binding of Ca to myofilaments
Overall, greater Ca transient release and greater force of contraction at myofilament level
Also get quicker relaxation, better filling of ventricle for next systole
What is the mechanism of action of Dobutamine/Dopamine?
Stimulates beta adrenergic receptors (primarily Beta 1), resulting in increased Calcium and better force of contraction
What is the mechanism of action of Milrinone?
Blocks PDE type III that converts cAMP to AMP
This allows for sustained levels of cAMP, resulting in increased Calcium and better force of contraction
How do inotropes change the Starling curve?
Decreases LV filling pressure
Increases CO
What is a negative effect of Beta1 receptor activation in the heart?
Increased automaticity - can lead to ventricular arrhythmias
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What non-cardiac effects does dopamine have?
Vasodilation of splanchnic and renal artery beds
Which inotrope is preferred: dobutamine or dopamine?
Dobutamine
Dopamine will increase HR (not desired since inotrope already increases contractility and increasing HR as well would increase cardiac work too much)
Dopamine will increase TPR via alpha1 effects (not desired since it will increase afterload)
Dopamine will increase preload
What is the mechanism of action of digitalis as an inotrope?
Inhibition of membrane Na/K-ATPase
Increased intracellular Na leads to increased intracellular Ca via Na-Ca exchanger
Increased cellular Ca is sequestered into SR, allows for greater release of Ca with next depolarization
More SR calcium released = greater force of contraction
What are the non-inotropic effects of digitalis?
Improved carotid baroreflex sensitivity –> Decreased sympathetic tone
Increased cholinergic receptor sensitivity –> Increased vagal tone
When used at therapeutic levels, will digitalis produce an inotropic effect?
No
Inotropic effects at levels near 1.4 ng/ml
Dosage recommendations are <1 ng/ml
What is the current therapeutic window of digitalis?
0.5-0.9 ng/ml
What are toxic effects of digitalis?
Excessively slow HR Arrhythmias Hypokalemia --> increased binding to Na/K ATPase --> increased chance of toxic arrhythmias GI abdominal cramping Ophthalmology: yellow-green halos
What are clinical uses of digitalis?
Treatment of rapid heart rate due to atrial fib or flutter
Treatment of HF patients in normal rhythm who are still symptomatic on standard therapy
