Drugs For Heart Failure Flashcards
what is an inotropic agent
agent that modifies the force or speed of contraction of myocardium
what are some positive inotropic agents and what are they used for
cardiac glycosides like digoxin
used to directly treat myocardial dysfunction
-increase contractility
systolic heart failure effects
reduced CO and contractility
reduced ejection fraction below 45%
respond to positive inotropic agents
diastolic failure effects
from hypertrophy
CO reduced
ejection fraction may be normal
does not rewspond to postive intotropic agents
cardiac glycosides
example and clinical use
digoxin
used to treat heart failure and a fib
half life of digoxin for pts with normal fenal function
36-48 hours
in pts with renal insufficiency (or older pts) half life increases to 3.5-5 days
pt taking what may increase renal digoxin clearnace
pts with HF taking vasodilators or sympathomimetic agents
Digoxin MOA
-2 desired effects
inhibition of membrnae bound sarcolemma Na+/K+ ATPase
-casues increase in contraction of cardiac sarcomere
- improves contractility
- prolongs refractory period of AV node in pts with SVT arrhythmias (no affect on preload or afterload)
how do cardiac glycosides ultimately increase myocardial contractility
by increaseing the releasable Ca2+ from the SR
length of AP and cardiac glycosides
may be shortened bc increased Ca2+ dependent K+ channel activity elevated
-promotes K+ efflux and more rapid repolarization
parasympathomimetic effects are inhibtied by
atropine
digoxin and electrical cardiac effects at therapeutic levels
parasympathomimetic effects
-cholinergic innervation is more concentrated in the atria, resulting in increased actions of digoxin on atrial and AV nodes compared to purkinje or ventricular fnct
electrical cardiac effects at toxic levels
depol of resting potential
marked shortening of AP
appearance of oscilatory depolarizing afterpotentials
most common cardiac manifesations of digoxin toxicity include
changes to AV junctional rhythm
premature ventricular depol
bigeminal rhythm
2md degree av block
toxicity of digoxin
heart: arrhythmias
GI: anorexia, nausea, vomiting, diarrhea
CNS: vagal and chemoreceptor trigger zone stimulation can cause GI symptoms, disorientation, hallucinations, visual distrubance and or changes
Gynecomastia: rare and can affect men
digoxin and hyper/hypokalemia
hyper can reduce effects of digoxin toxicity
hypokalemia enhances effect
____calcemia and ___magnesemia increase risk of digoxin incued arrhtyhmia
hypercalcemia
hypomagnesia
what are the bipyridines
inamrinone and milrinone
bipyridine administration
only parenteral, short term therapy
bipyridine MOA
- inhibits what enzyme
- effect on heart
- effect on calcium
- effect on vasculature
- effect on CO and afterload
inhibits PDE3 which usually degrades cAMP and cGMP so there is an increase in each
- increased cAMP in heart result in direct stimulation of myocardial contractility and acceleration of myocardial relaxation
- cAMP dependent PKs in heart phosphorylate and activate voltage gated Ca2+ channels and increase the amt of Ca2+ entering cell during AP
- increased concentration of cAMP in vasculature
- vasodilation by inactivating myosin LCK
-PDE3 inhibitors increase CO and decrease LV afterload
inamrinone toxicity
nausea, vomiting, arrhythmias, thrombocytopenia, and liver enzyme changes
milrinone toxicity
arrhythmias
B adreneergic agonist in HF
dobutamine
MOA of dobutamine and dopamine
increase cAMP–>PKA–>phosphorylation of substrates that enhance Ca2+ dependent contraction and speed relaxation
dobutamine is B agonist of choice for management of pts with
systolic dysfunction and HF
dobutamine hemodynamic effect
increase in stroke volume due to its positive inotropic action and increase in CO
major side effect of dobutamine
tachy and arrhythmias
DOPAMINE AND HF low dose
-may be useful in pts if there is a need to raise BP
- at low doses, causes vasodilation
- cAMP dependent relax and stimulating presynaptic D2 receptors inhibiting norepinephrine release and action on a-adrenergic stimulation of vascular SM)
dopamine at intermediate dose
directly stimulates B receptors on heart and vascular sympathetic neurons
enhances cardiac contractility and neural norepinephrine release
high dose dopamine
causes peripheral arterial and venous constriction via a-adrenergic receptor stimulation
-good for pts where circulatory failure is result of vasodilation like sepsis and anaphylaxis
thiazide diuretics are most freq used in treatment of
systemic hypertension and have more restricted role in treatment of HF
loop diuretics are widely used in
the treatment of heart failure
potassium sparing diuretics
shown to improve survival in pts with advanced heart failure via a mechanism independent of diuresis
vasopressin (ADH) antagonist name, MOA, toxicity
conivaptan
blocks ADH receptors (V1a and V2)
can cause hypernatremia, nephrogenic diabetes insipidus
selective ADH antagonist
tolvaptan blocks V2 ADH receptors
inhibtior of actions of angiotensin II will reduce what
preload (intravascular volume reduced by blocking aldosterone secretion)
afterload (via vasodilation)
what causes reductino in mortality and morbidity of HF pts when taking ACEI
kinins no longer degraded so stimulate NO, cGMP, vasoactive eicosanoids
-these prevent angiotensin II from cardiac and remodeling
ARBS block what receptor
AT1
venodilator
isosorbinde dinitrate
MOA of isosorbide dinitrate
release NO and activates guanylyl cyclase
-venodilation and reduces preload and ventricular stretch
AE isosorbide dinitrate
postural hypotension, tachy, headache
isosorbide dinitrate useq
in actute and chronic HF as well as angina
arteriolar dilators
hydralazine
- direct vasodilation of arterioles, little effect on veins
- reduces BP and afterload, increased CO
AE hydralzine
tachy, fluid retention, lupus like syndrome
combined arteriolar and venodilator
nitroprusside
MOA nitroprusside
release NO and activates guanylyl cylase
use nitroprusside
acute cardiac decompensation and HTN emergencies
Nesiritide use
actuely decompensated HF with dyspnea at rest or with minimal activity
Nesiritide MOA
binds guanylate cyclase receptor on vascular SM and endothelial cells–>increase cGMP–>SM relaxation
AE nesiritide
excessive hypotension
reports of significant renal damage and death
B adrenergic receptor blockers used to treat HF
- how long required until improvement noted
- dose to administer
bisoprolol (B1 selective antagonist)
carvedilol (non selective B antag, a1 antag)
metoprolol (B1 selective antag, mild to mod HF)
- several months
- also administrer at low doses to prevent worsening of HF due to antagonism of catecholamine effects
sodium removal danger
thiazide or loop diuretic induced sodium loss causes secondary loss of potassium
-dangerous if pt is taking digoxin–>increase its action and cause arrhythmnias
first line therpay for chronic heart failure
ACEI with diuretics
vasodilators: in pts with high filling pressures, in whom principal symtom is dyspnea ___ dilators most helpful in reducing filling pressures and sympoms of pulmonary congestion
venous
vasodilators: in pts with fatigue due to low left ventricular output, ___ may help increase CO
atrial dilators
when is digoxin given
if diuretics and ACEI fail to control symptoms
-small therapeutic window
