drugs used in heart failure Flashcards
inotropic agents
byryridines
cardiac glycosides
beta-adrenergic receptor agonists
bypyridines
-rinone
beta-adrenergic receptor agonists
dobutamine
dopamine
agents w/o inotropic effects
diuretics ACE inhibitors ARBs vasodilators beta-adrenergic receptors blockers natriuetic peptide
loop diuretics
-bumatanide
furosemide
torsemide
thiazide diuretics
HCL
chlorathiadone
aldosterone antagonists
eplerenone
spirolactone
ASH antagonists
conivaptan
tolvaptan
ACE inhibitors
-pril
ARBs
-sartan
vasodilators
isosorbide dinitrate (venous)
hyralazine (arterial)
nitroprusside (aa and vv)
beta blockers
-olol
carvediol
natriuretic peptide
nessiritide
diuretics and inotropic agents
increase quality of life and treat symptoms
do not decrease mortality
reduce mortality
ACE inhibitors, ARBs, beta-blockers, aldosterone recepotr antagonists
systolic failure
reduced CO and contractility
reduced EF (<45%)
typical of acute failure
responds to positive inotropic effects
diastolic failure
occurs as a result of hypertophy and stiffening myocardium
CO reduced
EF may be normal
does not typically respond to positive inotropic agents
digoixin
only glycoside available in US HF and Afib enters CNS normal renal fnx- 1/day vasodilators can increase clearance
digoxin pharmacodynamics
inhibits membrane-bound NA/K ATPase-> blocks Na/Ca exchanger -> more intracellualr Ca ->increases contraction of cardiac mm
effects of digoxin
improves contractility and prolongs refractory period of AV for treatment of supraventricular arrhythmia’s
digoxin and ANS
increases parasympathetics and reduces sypathetics
increases refractory period of AV node
digoxin toxcity
AV junctional rhythm PACs bigeminal rhythm second degree AV block tachycardia-> Vfib -> death
at toxic levels increases sympathetics
digoxin SA node
therapeutic dose- decrease rate
toxic dose-decrease rate
digoxin atrial mm
therapeutic dose- decrease refracotry period
toxic dose-decrease refractory period, arrythmias
digoxin AV node
therapeutic dose- decrease condcution velocity, increase refractory period
toxic dose- decrease refractory period, arrythmias
digoxin purkinje system and ventriuclar mm
therapeutic dose- slight decrease in refractory period
toxic dose- extrasystoles, tachycardia, fibrillation
digoxin EKG
therapeutic doses: increased PR interval, decreased OT
toxic doses- tachycardia, fibrillation, arrest
digoxin toxicity GI
anorexia, nausea, vomiting, diarrhea
digoxin toxicity CNS
vagal and chemoreceptors trigger zone stimulation -> GI, disorientation, hallucinations, visual disturbances
other digoxin toxicity effects
gynocomastia rare in men
digoxin toxicity Tx
antidigoxin immunotherapy
digoxin and K
bind to competing sites on Na/K ATPase
hyperkalemia can reduce effects of digoxin
hypokalemia can potentiate toxic effects
digoxin and Ca and Mg
hypercalcemia and hypermagnesemia increase risk of digoxin-induced arrhythmias
byridines
short term support of circulation in acute decompensated HF
may increase mortality if used long term
only parenteral
byridines MOA heart
selective inhibition of PDE3 -> increase cAMP -> direct stimulation of myocardial contraction and accelerated relaxation -> increased CO
byridines MOA vessels
inhibit PDE3 -> increase cAMP -> balances aa and vv dilation w/decrease in TPR and pulmonary resistance -> less work of left and right heart
caffeine
nonspecific PDE inhibitors -> limited by side effects
byridines toxicity
inamrinone- nausea, vommiting, arrhythmias, thrombocytopenia, liver enzyme changes
milirinone- arrhythmias
beta adrenergic and dopaminergic agents MOA
short term use (long term may increase mortality)
stimulate cardiac myocyte D1 R and beta 1 R
Gs -> AC -> cAMP -> PKA -> Ca -> increase contraction and speed relaxation
dobutamine
stimulates beta 1 choice drug for systolic dysfunction and HF increase in SV and CO can cause excessive tachycardia parenteral
dopamine low doses
vasodilation via D1 on smooth m and D2 on presynaptic sympathetics
dopamine intermediate doses
directly stimulated beta Rs on heart and vasculature sympathetics -> increased CO and increased NE release
dopamine high doses
peripheral aa and vv constriction via alpha 1
may be desirable in patients where circulatory failure is result of vasodilation
loop diuretics
heart failure
thaizide diuretics
systemic HTN
more effective in treating HF when combined w/loop
K sparring diuretics
relatively weak, but shown to improve survival in advanced HF via a mechanism other then diuresis
aldosterone antagonists
aldosterone may cause mycardial and vascular fibrosis and baroreceptors dysfunction
antagonism improves survival
ADH antagonists toxicity
hypernatremia, nephrogenic DI
ADH antagonists and HR
use is controversial
ACE inhibitors
- reduce TPR -> reduce afterload
- decrease sympathetics
- reduce long term remodeling of heart and vessels (ACE is same enzyme as kinase II) therefore increases bradykinin levels
- potentiate effects of diuretics in HF
ACE inhibitors adverse effects
angioedema, cough, hyperkalemia
ARBs
angiotensin II R blockers
block AT1, but beneficial effects of AT2 intact
ARBs do not alter bradykinin metabolism
should be considered in patients intolerant to ACE inhibitors
isosorbide dinitrate
NO released when drug metabolized -> increased cGMP-> venodilation and reduces preload and ventricular stretch
used in acute and chronic HF, angina, and HTN emergencies
long term limited by tolerance
isosobide dinitrate adverse effects
orthostatic hypotension, tachycardia, headache
nitroglycerin
venodilator used for acute decompensated heart failure
hydralazine
stimulates release of NO from endo -> vasodilation aa -> reduces BP and afterload -> increased CO
used in combo w/nitrates to reduce mortality in HF and HTN emergencies
hydalazine toxicity
tachycardia, fluid retention, lupus like syndrome
nitroprusside
spontaneously converted to NO -> marked vasodilation of aa and vv -> reduces preload and afterload
used for acute cardiac decompensation and HTN emergencies
nesiritide
recombinant form of BNP for acute decompensated HF w/dyspnea at rest
cases smooth mm relaxation and reduced endothelin production
vasodilation, natiuresis, diuresis counter acts effects of angtiotensin and NE
IV
adverse effects of nesirtide
excessive hypotension
beta blockers
improve contractile function
attenuation of maladaptive catecholamine induced cardiomyocyte toxicity
favorable effects on remodeling
reduce myocardial O2 consumption
decrezse frequency of unstable angina
may take several months before benefit is seen
Na removal
thiazide or loop diuretics cause loss of Na which leads to secondary loss of K
dangerous if on digoxin
hypokalemia Tx
addition of ACE inhibitor or K sparring diuretic, or supplementation
HF w/o edema first line Tx
ACE inhibitors w/diuretics
ARBs should be used if patients intolerant to ACE inhibitor
vasodilators in african americans
hydralazine and isosorbide dinitrate if they cannot tolerate or standard therapy no effective
