Heart Failure Pharmacology Flashcards
goals of HF treatment
prevent patients from ever getting symptomatic HF
focus on stage A and B HF for prevention
once symptomatic, prevent hospitalization
prevent progression to stage D HF
Stage A HF treatment
treat hypertension
encourage smoking cessation
treat lipid disorders
encourage regular exercise
discourage alcohol intake and illicit drug use
control metabolic syndrome
drugs: ACEI or ARB in appropritae patients
Stage B HF treatment
all measure under A
drugs: ACEI or ARB as well as beta-blockers in appropriate patients
Stage C HF treatment
all measures under stages A and B
dietary salt restriction
drugs for routine use: diuretics for fluid retention, ACEI, beta-blockers
drugs in selected patients: aldosterone antagonist, RBs, digitalis, hydralazine/nitrates
devices in selected patients: biventricular pacing, implantable defibrillators
Stage D HF treatment
appropriate measures under stages A, B, or C
decide on appropriate level of care
options are end-of-life care/hospice
extraordinary measures include heart transplant, chronic inotropes, permanent mechanical support, experimental surgery or drugs
symptoms of HF
low exercise capacity - decreased CO
dyspnea - pulmonary edema
orthopnea - increased venous return when supine
nocturia - increased venous return when supine
swelling, weight gain - salt and water retention
signs of HF
increased JVP - elevated RA pressure
rales - pulmonary edema
S3 - elevated LV filling pressures and stiff LV
hepatomegaly - systemic venous congestion
edema - transudation of fluid from capillaries
NYHA class I
no limitations of physical activity
NYHA II
slight limitation of activity
dyspnea and fatigue with moderate physical activity
NYHA III
marked limitation of activity
dyspnea with minimal activity
NYHA IV
severe limitation of activity
symptoms are present at rest
precipitating factors of HF
medication non-compliance
dietart indiscrtion
increased metabolic demands (fever, infection, anemia, tachycardia, hyperthyroidism, pregnancy)
increased circulating volume (increased preload)
increased afterload (uncontrolled systemic hypertension, pulmonary embolism)
reduced CO due to either reduced contractility or reduced stroke volume/abnormal heart rate
principles of HF treatment
identify underlying etiology
eliminate precipitating cause
ameliorate HF symptoms
modulate maladaptive neurohormonal response
improve long-term survival
steps to prevent heart failure
control blood pressure
control diabetes
control lipids
smoking cessation
weight control
early recognition and treatment of acute coronary syndromes
treatment of symptomatic HF
identify and treat the underlying etiology of HF
eliminate precipitating factors
ameliorate HF symptoms
modulate maladaptive neurohormonal response
improve long-term survival
treatment of heart failure with reduced EF (systolic HF)
improve Frank-Starling relationship in acute and asymptomatic patients
neurohormonal antagonists - reverse remodel and prolong life, pharmacogenomics is a possibility
devices to preevent sudden death
inotropic devices
heart replacement/support
treatment of heart failure with preserved EF (diastolic HF)
so far randomized controlled trials have been disappointing
find and treat underlying etiology
agggressively treat hypertension
coronary revascularization
if atrial fibrillation - control rate and/or convert to normal sinus rhyth
treat comorbidities
treatment of acute pulmonary edema in acute decompensated HF
LMNOP
L - loop diuretics, acutely venodilate and then natriuresis
M - morphine, venodilator to decrease sensation of dyspnea
N - nitrates, venodilator to increase pulmonary venous capacitance
O - oxygen, increased supply at a time when oxygen demand is high
P - positive pressure ventilation, improve oxygenation and decrease venous return, increases contractility
after acute stabilization, medicate underlying problem
hemodynamic goals for achieving symptom relief and stabilization in acute decompensated EF
reduce right and left heart filling pressures
reduce systemic vascular resistance
increase cardiac output
signs of congestion
orthopnea, increased JVP, rales, ascites, leg swelling
signs of poor perfusion
cool extremities, decreased BP, decreased pulse pressure, sleepy/obtunded, worsening renal function, decreased urine output
cold and wet
congested with poor perfusion
use vasodilators first and then inotropes
warm up and then diurese
cold and dry
no congestion but poor perfusion
end-stage HF vasodilators, inotropes
LVAD
heart transplant
warm and wet
congested but well-perfused
diurese and uptitrate HF meds
warm and dry
reconsider HF diagnosis
diuretics
most comonly used are secreted into the nephron via the proximal tubule (except aldosterone antagonists)
therefore doses need to be increased in patients with chronic kidney disease
categorized by site of action
types of diuretics
proximal tubule - acetazolamide, rarely used
thick ascending limb of loop of henle - loop diuretics
distal convoluted tubule - thiazide diuretics
collecting ducts - potassium-sparing diuretics
loop diuretics
improve symptoms but increase neurohormones
ex. furosemide, torsemide, bumetanide, ethycrinic acid (important, ototoxicity)
thiazide diuretics
HCTZ, chlorthalidone, chlorhiazide, metolazone
less potent than loop diuretics but can be very potent in combination
potassium sparing diuretics
triamterene and amiloride
rarely used
aldosterone-antagonists, improve mortality
deleterious effects of aldosterone
prothrombotic effects
vascular inflammation and injury
potassium and magnesium loss
central hypertensive effects
endothelial dysfunction
ventricular arrhythmias
cardiovascular disease
sodium retention
catecholamine potentiation
myocardial fibrosis
types of vasodilators
intravenous
hydralazine
nitrates
ACE-inhibitors and angiotensin receptor blockers (ARBs)
intravenous vasodilators
nitroglycerin
nitroprusside
nesiritide
nitroglycerine
primarily a venodilator
good for patients who are warm and wet but not patients who are cold because they can acutely worsen hypotension
nitroprusside
mixed venous and arterial vasodilator
vesodilator of choice if a patient is cold because it won’t decrease preload as much as other agents
nesiritide
recombinant BNP natriuretic peptide that also dilates veins and some arteries
do not use in hypotensive patients because it may increase mortality or renal failure
oral vasodilators
hydralazine
nitrates
ACE inhibitors
ARBs
hydralazine
pure arterial vasodilator
reduces SVR, thereby increasing CO and can paradoxically increase BP
nitrates
venodilator
increased pulmonary venous capacitance, decreased pulmonary venous pressure, decreased hydrostatic pressure, decreased pulmonary edema
use with caution in hypotensive patients who may be preload-dependent
ACE inhibitors
block deleterious effects of angiotensin II
increases bradykinin, which leads to vasodilation and cough
angitensin receptor blocekrs (ARBs)
block angiotensin II receptor
no cough, but no bradykinin-induced vasodilation
better than ACE inhibitors because they block the receptor completely
there is no cough, but benefits of high bradykinin is gone
inotropes
all IV inotropes increase mortality in acute decompensated heart failure, so use with caution
beta-adrenergic agonists
phosphodiesterase inhibitors
calcium sensitizers
digitalis (digoxin)
digoxin
decreases hospitalization but not mortality
optimal concentration between 0.5 and 0.8 ng/ml
higher dizes increases mortality
blocks Na/K-ATPase which increases calcium in the cell due to the sodium/calcium pump
adrenergic modulation
beta-blockers
indicated for all classes of systolic HF
use after stabilization of the patient, can cause acute decompensation, so start low and be cautious
if a patient is on chronic beta-blocker therapy and gets admitted for ADHF, try to keep on beta-blocker if possible
reduce mortality
beta-adrenergic agonists
ex. dobutamine, dopamine, and norepinephrine
can cause increased contractility, increaed HR, peripheral vasodilation, and peripheral vasoconstriction depending on the drug
dobutamine is most commonly used
phosphodiesterase inhibitors
amrinon and milrinone
milrinone is the only one clinically used
these work intracellularly and bypass the beta-receptor by increasing cAMP
also increase contractility and cause peripheral vasodilation
calcium sensitizers
levosimendan
sensitizes myocytes to calcium, which increases contractile force
no evidence of outcome benefits
limitation of drugs in heart failure
too many
need to be taken without specified periodicity
side effects/toxicity
drug/drug interactions
costly
non-pharmacologic therapies
lifestyle / dietary chagnes / exercise
treatment of comorbidities
ultrafiltration - alternative to diuretic therapy
cadiac resynchronizatino therapy (CRT)
implantable cardiac defibrillator (ICD) therapy - used in patients in class I-III HF but not patients with class IV
surgical therapies - mitral valve repair, ventricular assist device, cardiac transplantation
cardiac resynchronization therapy (CRT)
indicated in symptomatic patiwhts with NYHA class III or IV with persistent symptoms despite optimal medical management
patients who most likely have intraventricular and interventricular electrical and mechanical dyssynchony
by pacing RV and LV simultaneously, cardiac function can improve in these patietns
ventricular dyssynchrony
uncoordinated electrical and mechanical contraction of the ventricles
may involve disruption of collagen matrix - impairs electrical condcution and mechanical contraction or efficiency
associated with woprse prognosis and impaired hemodynamic function
