Drugs for Heart Failure Flashcards
Principal symptoms of HF
Dyspnea and fatigue
Exercise intolerance
Fluid retention
Some present primarily with exercise intolerance, others fluid overload
People w/ HTN have a ___ increased risk of HF
6x
need to manage HTN
Several complex compensatory mechanisms to maintain cardiac output and oxygenation of vital organs
(4)
Increased sympathetic tone
Activation of renin-angiotensin-aldosterone system: Sodium and water retention
Cardiac remodeling (ventricular dilation and hypertrophy) (we don't have meds that affect this)
Other neurohormonal adaptations – endothelial hormones, vasopressin, natriuretic peptide
Sympathetic Autonomic Nervous System as it pertains to HF
Initially NE causes increased inotropic and chronotropic effects –> maintain near-normal CO and preserve perfusion of vital organs (CNS, heart)
Vasoconstriction in skin, GI, renal circulation decreases perfusion to these organs, and increases cardiac work load via –> SVR
in response to NE
beta1 receptors-G protein effector system ____ and with
beta 2 _______
beta1 receptors-G protein effector system downregulation
beta 2 not affected
this is why we give BB even though we see a further decrease in HR initially
but if we block the beta receptor you can re-sensitize the body to the NE that is there
w/ first dose sxs can worsen
ANP is the bodies
natural diuretic
Released from specialized cells in atrial (ANP) or ventricular (BNP) muscle in response to stretching of myocytes
Results in direct arterial vasodilation, increased GFR, and diuresis
Low output failure
diminished volume of blood pumped by a weakened heart in patients who have otherwise normal metabolic needs
High output failure
high metabolic demands due to underlying medical conditions (hyperthyroidism, anemia) –>healthy heart, pumps normal to high volume of blood; –> heart becomes exhausted fromincrease work load and unable to meet demand
High output failure tx
need to tx underlying condition
Ejection fraction (EF) < 40% Reduced myocardial muscle contractility Enlarged heart (dilated left ventricle)
HFrEF – systolic heart failure
Normal EF (>50%), decrease SV & CO
Normal left ventricular contractility
Stiff left ventricle with impaired left ventricular filling
HFpEF – diastolic heart failure
Heart Failure Etiology
Hypertension Valvular disease
Amyloidosis, sarcoidosis Coronary ischemia
Pericarditis
Drug Induced
Alcoholism Scarring post-MI
Enlarged left ventricular septum (hypertrophic cardiomyopathy)
Symptoms of heart failure
SOB Cough Orthopnea PND (paroxysmal nocturnal dyspnea) DOE (dyspnea on exertion) Reduced exercise tolerance Fatigue Weight gain Edema
Physical findings in HF
Tachycardia
Increasing weight
JVD or hepatojugular reflex
Presence of S3
Laterally displaced apical impulse
Fluid retention
Pulmonary crackles or
wheezes
Peripheral edema
Hepatomegaly
Objective test to measure EF (2-D echocardiogram with Doppler flow studies or cardiac catheterization)Non-pharmacologic Interventions To reduce risk of new cardiac injury
Attain or maintain normal weight
Smoking cessation
Alcohol consumption discouraged
Manage co-morbities (HTN, DM, HLP)
Interventions To reduce risk of new cardiac injury Maintain fluid balance
Na restriction, daily weight, fluid restriction
what is structural heart dz (stage B)
vascular dz
remodeling
valve issues
stage A of heart failure
pts without strucutral heart diease but with
htn dm atherosclerotic dz obesity metabolic syndrome
or using cardiotoxins or with Fhx
1st line TX for HF
ACEI and BB
staging A B C D of HF
doesn’t move back and forth
A. no structural abnormalities but high risk
B structural disease but without sxs
C. structural disease with prior sxs
D, refractory HF
RAAS drugs
ACE and ARB
BB
not CCB
Diuretics provide what kind of control in HF
sx
two kinds of K sparing diuretics
aldosterone antagonists: spironalactonin and eplerenone
inhibitions of Na/k pump: triamterene and amiloride
two types of aldosterone antagonists
spironlactone and
eplerenone has less hormonal effects and is more specific for receptors in the kidney and less overall steroid effect
which diuretics are used in HF
loop
how often do you dose loop diuretics in HF
once a day
2x daily for HTN
what labs do you want to monitor on a loop
K
creatinin to monitor their renal function
why do we worry about kidney function in loop diuretics?
decreased renal profusion through hypotension and decreased renal sufficiency
don’t want too dramatic of a diuresis
takes a while for interstitial fluid to redistribute back into the blood stream
Hypokalemic metabolic acidosis
name the loop diuretics (4)
which one can be used with a sulfa allergy
Furosemide Bumetanide Torsemide Ethacrynic acid " --->Only one that can be used w/ sulfa allergy
why do we loose Mg with loops
normally you get excess K seeping back into the tubule net positive charge results in the absorption of Ca and Mg
if you’re blocking this you loose Mg
wut? look into this later
what is the mechanism (if you have renal artery stenosis ) by which you will see renal failure with ARB and ACEI
blocking angiotensin and dialating efferent
you are blocking efferent
but if you have stenosis in the afferent arteriole
won’t have as much back pressure and wont’ have sufficient filtration
will lead to a dramatic rise in creatinine
what do we need to monitor in a pt taking ARB
” Monitor BP, renal fxn, for hyperkalemia since increase serum Cr and worsen renal function w/in 1-2 wks
ACEI names and dosages
Benazapril
Captopril
-6.25- 12.5mg tid
Enalapril
-2.5-5mg qd (20mg)
Fosinopril
-5-10mg qd (20mg)
Lisinopril
-2.5-5mg (20mg)
Moexipril
name ARBS
Candesartan -8-32mg qd Irbesartan -75-300mg qd Losartan -25-100mg qd Telmisartan Valsartan -80-320mg qd Azilasartan
Mechanism by which loop diuretics work that interferes with NSAIDS
giving a non steroidal blocks the production of prostaglandins through the COX pathway and negates HTN effect
angioedema with ACEI is there cross reactivity with ARBs?
no, it looks like you should wait 6 weeks after stopping the ACEI though
3 BB for cardio protection
Metoprolol XL
Carvedilol
Bisoprolol
Sacubitril and Valsartran (Entresto)
indication
patients with optimal dosing ACE/ARB and beta-blockers and MRA
CI with ACEI
MOA w/ BB in HF
Deactivation of SNS –> leads to B-receptor down-regulation, LVH, arrhythmia, cardiotoxic effects
they reduce mortality AS LONG AS they are dose appropriately
which BB for HF is non selective and is associated with alpha adrenergic blocking and antioxidant effects
carvedilol (coreg)
If pt has borderline BP and HF which BB would you be most likely to use
alpha blocking gives you unopposed beta 2
alpha blocking is vasodialating
metroprolol is more selective and is usually used in pts with lower blood pressure
however as long as you use appropriate dosing you could in theory use both
Metoprolol XL initial dosing for HF
and target
12.5-25mg 1xday
most people are 25 2x daily
Carvedilol (Coreg, generiic) initial dosing for HF
and target
initial dose 3.125mg bid, titrate at minimum q2 wks to target 25 – 50 mg bid
people will often see worsening of HF sxs initially because of up regulation initially
Bisoprolol (Zebeta) initial dosing for HF
and target
not used as frequently as carved or meto
initial dose 1.25mg qd; increase by 1.25mg q wk until 5mg qd, then increase by 2.5mg q4 wks to target dose 10mg qd
why do we give carvedilol with food?
Carvedilol should be given with food to reduce incidence of orthostatic hypotension
why should you not abruptly stop a BB
because you would have sns surge (rebound)
Ivabradine (Corlanor) MOA
slow heart rate through a different mechanism than bb
: inhibits f-channels in the SA node, prolonging diastole, reducing heart rate
Ivabradine (Corlanor) indicated for pts who…
on target dose of BB but still have HR over 77
BiDil is a combination of what two drugs
combination hydralazine 37.5mg (vasodilator) and isosorbide dinitrate 20mg
when is BiDil indicated
shown to further reduce mortality in AA population
hydralazine reduces….
ISDN reduces…..
MOA of BiDil
” Vasodilator
“ Mixed
Hydralazine: ↓afterload
ISDN: ↓preload
similar to an ACE because it addresses both
how do ACEI reduce preload and afterload
reduce vasoconstriction (afterload) and release of aldosterone (preload)
MOA of digoxin
Blocks Na-K-ATPase pump and therefore Na-Ca exchanger –>
↑Ca (intracellular) —> ↑contractility and have positive anotropic effect
two effects of digoxin
direct on AP duration
and PSNS effects (slower)
can block conduction in supraventricular arrhythmias
why does digoxin not reduce mortality? what is it doing?
does not actually save lives because of pro arrhythmic effect
just decreases sxs and hospitalizations
indications of digoxin
in stage III on pts already on ACEI and BB to minimize hospitalizations
maybe for afib too
1/2 life of digoxin
1.5-2 days
x 4-5 to get to a steady state
= week to a week and a half
ADE of digoxin
” AV block /arrhythmias (Prolonged PR interval)
“ —>Junctional rhythms, MAT w/ block, PAT, AF, PVCs,
VT, VF
” High risk hypokalemia
we see hypokalemia though with diuretics so this is an issue…
hallmark of digoxin toxicity
visual disturbances and halos around lights
digoxin levels at trough
.5-.9 ng/ml
make sure this is NOT during post distribution phase
have pt withhold meds in morning if you are running dig levels
takes 4 hours to distribute with IV
6-8 hours with PO
besides AV blocks and arrhythmias what side effects are we looking for that indicate toxicity
” Anorexia, N/D
“ Gynecomastia in chronic therapy
“ CNS: fatigue, weakness, psychic & visual disturbances (hazy, yellow-green vision)
digitilization
give loading dose over 24 hr period to allow time for distribution
what are we concerned about in a pt on Erythromycin or tetracyclines
knocks out bacteria in the gut and decreases absorbtion
DID with digoxin
Antacids, cholestyramine, colestipol, kaolin-pectin: reduced absorption due to adsorption
Erythromycin, tetracyclines
Erythromycin, tetracyclines
Laxatives, metoclopramide: reduced absorption due to increased gut motility
what can we do for a pt with an arrhythmia who we suspect has a dig overdose
Digibind
Drugs for Acutely Decompensated HF
Diuretics: loop +/- HCTZ or metolazone
metaolzaone
o Vasodilator: Nitroprusside or nitrate. Used in fluid overload to decrease preload
o Inotropes stimulate contraction; only used in people w/ low BP
why do we use Diuretics: loop +/- HCTZ in Acutely Decompensated HF
blocks sequential parts of the loop and dramatically increases diuresis
Nitroprusside
only given IV
potent vasodilator; activates guanyl cyclace leads to increase cGMP –> smooth muscle relaxation
Dilates both venous and arterial vessels – reduces preload and afterload
2 minute half life
used in immediate short term for rapid bp control
has both preload and afterload reduction for the mngmt of HF
Milrinone
only used short term for decomp in HF awaiting heart transplant
Both inotropic and vasodilating
Selectively inhibit phosphodiesterase F –III (cardiac and vascular cyclic-AMP-specific) cAMP Ca++ flux enhanced contractility
only used short term because it causes arrhythmias
b1-selective synthetic catecholamine which also activates b1 receptors
Increased myocardial contractility, HR and CO, but also increases myocardial oxygen demand
Given as long term infusion for 48-72 hours in patients with refractory HF or awaiting transplant
Dobutamine
Immediate metabolic precursor of NE
Activates D1 receptors in several vascular beds –> vasodilation (effect on renal vasculature may be of clinical importance; better than dobutamine); also activates B 1 receptors in heart
Dopamine
Drugs that INDUCE heart failure:
Negative inotropic drugs: BB, CCB, antiarrhythmics (disopyramide, quinidine)
Direct cardiotoxins: cocaine, amphetamines, anthracyclines (doxorubicin, daunorubicin)
Anti-TNF agents: etanercept, infliximab
Drugs that cause plasma volume expansion: NSAIDs, glucocorticoids, estrogens, androgens, black licorice, antihypertensive vasodilators (hydralazine, methyldopa, prazosin, minoxidil –> decrease RBF and activate RAAS), drugs high in Na
Drugs that cause plasma volume expansion
NSAIDs, glucocorticoids, estrogens, androgens, black licorice, antihypertensive vasodilators (hydralazine, methyldopa, prazosin, minoxidil –> decrease RBF and activate RAAS), drugs high in Na
