Heart Failure Treatment 2 Flashcards
Cardiac glycosides drugs
Digoxin (Lanoxin, Lanoxicaps)
Cardiac glycoside MOA
Inhibition of Na/K ATPase via preferential binding to the phosphorilated alpha subunits and inhibiting it
Extracellular K does what
Promotes de-phosphorylation of the alpha subunits which decreases the effectiveness of cardiac glycosides
How does contraction happen in cardiomyocytes?
Impulse leads to sodium entering through the fast sodium channels –> triggers an exchange of calcium and sodium which then leads to a huge amount o calcium to enter through L type channels
Calcium also comes from the sarcoplasma reticulum which leads to a ton oc Ca within the cell
This calcium then interacts with troponin or calmodulin which leads to phosphorylation of myosin light chain kinase which leads to interaction of actin and myosin which leads to contraction of the cells
How does relaxation occur in cardiomyocytes?
Sodium leaves the cell and potassium enters (3:2) via Na/K ATPase and the calcium leaves the cells and then leftover Ca is stored sarcoplasm reticulum
This leads to no phosphorylation and actually have de-phosphorylation
So where do cardiac glycosides come in on all of this?
They block the Na/K ATPase and other cells that let Ca out so this calcium is moved into the sarcoplasma reticulum and then less Ca has to come in to the cell which leads to a stronger contraction than before
Cardiac glycoside main effect
+ Inotropic effect
Increased vagal tone and decreased sympathetic activity
Increased AV refractory period
What does vagus activation do?
The heart slows down, which can be a good thing because it will rest during diastolic and during systolic it will contract with more force
Increased AV =
It takes longer for impulses to travel through heart and this is good because the heart rate will be lower
Ions and cardiac glycoside actions:
K+- promotes alpha subunit dephosphorylation in Na/K ATPase and decreased interation of cardiac glycosides with the pump
Hypercalcemia increases digoxin toxicity
Hypomagnesemia increases digoxin toxicity
Hypokalemia
potentiates digoxin effects, as well as toxicity
Hyperkalemia
Attenuates digoxin effects on the heart
Digoxin’s therapeutic window
Very narrow
- Effective: 0.5-1.5
- Toxicity: ~1.5
Digoxin special features
Unchanged in urine
- Can cause cardiac arrhythmias, anorexia, n/v, blurred vision and seizures
Dobutamine
Beta agonists in systolic dysfunction and HF
Stimulates B1 and B2 and alpha 1 antagnoist and agonists so this neutrilizes
Dobutamine Ultimately does what
Increase stroke volume via beta 1
slightly increases HR via beta 1
Modest decrease in peripheral resistance via beta 2
Dobutamine AE
Tachycardia and arrhythmias
Tolerance may develop
Epinephrine
Has beta and alpha activity but the beta is much more prevalent
Epinephrine does what?
Increase strength of contractility
Increase AV node conductance
Increase HR
(No change in peripheral resistance
Epinephrine has metabolic effects which
effects the lungs and airways as well as the eyes (via B2)
Epinephrine AE
HTN
Headache
Anxiety/confusion
Angina
Norepinephrine activity and does what?
Alpha and beta but more alpha
It causes vasoconstriction which increase peripheral resistance and may slightly increase or not change CO
Dopamine Low Doses
Less 2 mcg/kg/min
D1 receptors in vasculature causing vasodilation
Presynaptic D2 receptors causes decrease NE release
Direct effect on renal tubular epithelial cell causing increase natriuresis
Dopamine intermediate dose
2-5mcg/kg/min
Directly stimulate beta receptors in the heart and nerve terminal to increase cardiac contractility and NE release
Dopamine High Dose
5-15 mcg/kg/min
Stimulates alpha 1 receptors in the vasculature to cause vasoconstriction
Dopamine AE
Etopic beats, tachycardia, angina, HYPOtension, headache nausea
Milrinone (Primacor)
Short term support advanced HF
Increases cardiac contractility and decreases peripheral resistance
Selectively inhibits PDE in the myocardium and vasculature so it doesn’t not inactivate cAMP
B-agonist + Milirone
Increased effects
B-antagonists + B-agonists
No effect
B-antagonists + milrinone
Slightly increased effect
Stimulation of B1 and B2 lead to
Increase adenylyl cyclase and increase cAMP
Milrinone AE
Arrhythmia, hypotension, headache, thrombocytopenia
Myocardial injury + continuous SNS activation
Contributes to progression of contractile dysfunction
Prositive inotrope agents are predominantly used for
Acute HF (short term support of circulation
Beta adrenergic antagonists do what
Block harmful effects of activated SNS
Used to treat mild-to-moderate HF
Examples of Beta adrenergic antagonists in HF
Metoprolol (Toprol, Lopressor) and Carvedilol (coreg)
Metoprolol activity
Selective beta 1 adrenoceptor antagonist
Carvedilol activity
B1/2 and alpha 1 adrenergic receptor antagonists
+ Calcium channel blocking activity
