Inotropic Agents in CHF Flashcards
What does digoxin do?
blocks Na/K+ ATPase
How does digoxin affect inotropy
1) block Na/K+ ATPase
2) accumulate Na+ inside cell
3) Na+ exchanged for Ca2+ entry
4) Ca2+ stored in SR
5) incr # of crossbridge btwn actin/myosin
6) incr force of contraction –> inotropy
how does digoxin affect sympathetic NS?
baroreceptors lose sensitivity with digoxin
digoxin incr parasympathetic NS, incr SA and AV node
decr HR
Hemodynamic effects of Digoxin
incr CO
Decr WEdge pressure (from lungs to LA)
incr LV ejection fraction
Neurohormonal effects of Digoxin
1) parasympathetic incr
2) incr baroreceptor sensitivity –> parasymp
3) decr NE
4) decr RAAS
Electro effects of Digoxin
1) slow SA and AV node
How is Digoxin excreted
renally = 70%
Bioavailability of Digoxin at various forms
a) oral
b) IV
a) oral = 75%
b) IV = 100%
metabolism of Digoxin
blocks P-glycoprotein (normally pumps drug out)
accumulate digoxin
Time to peak steady state of digoxin
7-10 days
(half-life = 38 hrs) * 4-5
what is therapeutic serum concentration of digoxin
between 0.5 -1 ng/mL
which drugs have DDI with digoxin due to inhib P-glycoprotein
Quinidine Verapamil Amodarone Dronedarone Propafenone Itraconazole Erythromycin Clarithromycin
What three electrolyte abnormalities cause digoxin toxicity?
1) hypokalemia - incr dig binding
2) hypercalcemia - incr Ca2+ abs into myocytes, incr inotropy
3) hypomagnesemia - cause arrhythmias
Symptoms of Digoxin TOXICITY
1) N/V/ABD PAIN
2) CONFUSION
3) HYPERKALEMIA
4) BRADYKARDIA/ARRHYTHMIA
5) visual effect
Digoxin immune fab mechanism
binds Digoxin and doesn’t allow Digoxin to bind receptor
–> toxicity (arrhythmia, bradycardia, heart block)
Effects of digoxin
reduce # of HOSPITALIZATIONS for worsening heart failure but DOES NOT decrease mortality
WHICH patients benefit from digoxin?
NYHA Class 3 and 4 and those with low ejection fraction
Does digoxin help HFpEF patients?
NO EFFECT
GENERAL approach to treat Heart failure
1) reduce congestion and volume overload with sodium and fluid restriction + diuretics
2) may add IV vasodilators
3) rarely use inotropes
Mechanism of action of dobutamine
β-1 agonist to increase contractility,
slight peripheral vasodilation
when to use dobutamine
ADHF short-term management - “Cold & wet”
recommend if hypotensive
Half life of dobutamine
2 minutes
side effects dobutamine
tachyarrhtyhmia
mechanism of action of milrinone
PDE inhibitor
moderate peripheral vasodilation
when to use milrinone
ADHF short term management- cold and wet
recommend if receiving a beta blocker
side effects milrinone
POTENT VASODILATOR
hypotension
thrombocytopenia
increased LFTs
general rule with inotropes
DO NOT USE IF YOU CAN AVOID
Dopamine mechanims
precursor of norepinephrine
stim adrenergic receptors + release norepi from nerve terminals
Benefits of dopamine at different doses
R I P
renal (dopaminergic) at low dose
inotrope (beta receptor effect) at med dose
Pressor (alpha receptor effect) at high dose
side effects of dopamine
arrhythmias
angina
incr HR
incr vascular resistance
