CHF Drugs
CHF:  Cardiac output at the expense of intravascular volume overload.
Activation of SNS and Renin-Angiotensin System produces: Norepinephrine, Angiotensin II, ADH (Vasopressin), Aldosterone
Norepinephrine, Angiotensin II, and ADH are part of neurohormone storm.
They produce increase in TPR = increase in afterload = decrease in CO.
Renal Vascular resistance = GFR
CO = Renal blood flow + GFR
Therefore, patient w/ decompensated heart failure is characterized as a patient with decreased CO at the expense of increased TPR
and intravascular volume overload.
Purpose of Pharm Therapy: decrease TPR and afterload, and increase CO, Renal blood flow, and urine output.
Drug
MOA / Pharmacodynamics
Furosemide (Lasix): dose 20 mg/day - >400 mg/day
Bumetanide: shorter acting, better GI absorption
(same w/ Toresmide)
Thiazide:
Metolazone
HCTZ
Don’t reduce
mortality, just
help symptoms!
Angiotensin
Converting
Enzyme Inhibitors
(ACE Inhibitors)
Enalapril (2x/day)
Lisinopril (1x/day)
REDUCE
MORTALITY
SE / Contraindications
Acts at loop of henle to prevent sodium
reabsorption and thus increasing urine production
Loop Diuretics
Furosemide (40mg)
Bumetadine (1mg)
Toresmide (10-20mg)
ACE Inhibitor: Inhibits angiotensin-converting enzyme to
prevent angiotensin II (a vasoconstrictor) production. Thus,
ACE inhibitors cause angiotensin I levels to increase.
Preventing reabsorption of sodium leads to
increase Na load in distal convoluted tubule – you
start to increase avidity to Na (basis of Lasix
resistance). Therefore, you increase dose and add
a thiazide (inhibits sodium reabsorption in distal
convoluted tubule).
-Levels of bradykinin increase which contributes to
decrease in TPR and vasodilation.
-Angiotensin II typically stimulates hypothalamus to
drive thirst mechanism and stimulates posterior
pituitary to generate ADH in addition to adrenal
gland stimulation of aldosterone.
Therefore, ACE-I will:
-  products of the Neurohormone l Storm
-  Cardiac Output
-  symptoms of Heart Failure
-  Survival
-  vascular activation, atherosclerosis progression,
and thrombosis
-  fibrinolysis
Wide & safe dosing: 2.5-40 mg/day
Orally active & well absorbed
High doses of furosemide  ototoxicity
Sulfur allergy!!! (Only ethacrynic acid is
sulfur free).
Associated w/ arrhythmias due to K and
Mag wasting.
SE: Hypovolemia, Hypokalemia,
Hypotension, Renal Failure, Alkalosis
SE of Thiazide: hypokalemia
Bradykinin is responsible for the SE profile
- chronic hacking dry cough
- hyperkalemia
- angioneurotic edema (class specific to if
you get it on one ACE inhibitor, you’ll get
it with all.
SE profile occurs in 20 % of all patients.
Considerations: Class III & IV HF 
hypotension if not monitored properly,
which will decrease renal function and
injure kidneys more.
Over time, you may get ACE escape (so
then you start to use ARBs)
Drug
MOA
Pharmacodynamics
SE / Contraindications
AT Receptor
Antagonists
Losartan
Valsartan
Angiotensin Receptor Blockers (ARBs): direct
blockage of AT 1 receptor, which is
responsible for vasoconstriction, ADH, and
aldosterone release.
By blocking AT-1, we would block effects of angiotensin II on
receptor, therefore decreasing TPR, decrease aldosterone, and
improve patients.
Don’t use WITH ACE-I: combination may
increase risk of renal failure and hyper
REDUCE
MORTALITY
Beta-Blockers
Carvedilol (B1/B2)
Metoprolol (B1)
Bisoprolol (B1)
Bind tightly to beta receptor blocking the
effects of Norepinephrine in the mediator of
SNS.
REDUCE
MORTALITY
Need to monitor K+ and serum Cr!
-No increase in bradykinin.
-Best used in ACE intolerant (cough)
-Orally active: once a day, dose needs to be titrated
-Losartan – just not as effective as ACE inhibitors
CV Effects of Beta-Blockers in CHF Patients
-  HR =  tachycardia of Heart Failure (Important in patients with
Coronary Artery Disease = Myocardial Oxygen Consumption)
- Total Peripheral Resistance =  Myocardial Afterload
-  A-V nodal conduction = (able to slow the ventricular response
rate in Atrial fibrillation)
- Combined ACE-I & BB in RCTs demonstrate  Survival
-Bronchospasm
-Slowing of AV conduction (heart block)
-Hypotension
-Depression (esp in elderly)
-Impotence can limit use in young males
Metropolol: 12.5 mg – 100 mg (extended release daily & 2x/day)
- Goal dose is 200 mg
Carvedilol: 3.125 mg – 25 mg twice a day
Aldosterone
Inhibitors
Spironolactone
Eplerenone
REDUCE
MORTALITY
ADH Inhibitors
Hydralazine and
Nitrates
REDUCE
MORTALITY
Direct inhibition of the mineralocorticoid,
Aldosterone, thereby inhibiting SodiumPotassium exchange in the kidney and
preventing the excretion of potassium
Prevents aldosterone, which normally activates fibroblasts and
lays out more scar tissue.
Commonly called potassium sparing diuretics, but in actuality
they’re weak diuretics
Oral – 12.5 – 50 mg/day
Drugs in combination w/ ACE-I and B-blockers in patients w/
dilated cardiomyopathy improve symptoms and reduce mortality
by decreasing myocardial fibrosis.
Hyperkalemia is a direct effect of the
drug, risk factors: Age > 70, Decreasing
Renal Function: Cr > 2.3 mg%, Inability to
monitor potassium
Spironolactone: produces a 20 %
incidence of gynecomastia in the male
Eplerenone: No estrogenic stimulation
but a weaker aldosterone antagonist
Need to monitor K+ and serum Cr!
ACE-I just reduces death from HF, but beta blockers and
aldosterone antagonists reduce sudden death (theory is you
decrease scarring in heart so less chance of arrhythmias).
ADH inhibitors are available but only for correction of hyponatremia
They have NO beneficial effect on either morbidity or mortality in heart failure patients over and above ACE Inhibitors, Beta-Blockers, and Aldosterone Inhibitors
Vasodilators!
Vasoconstriction is bad especially if you have a myopathic heart because increase in afterload (blood pressure in this case) will decrease stroke volume. With a
myopathic heart, you’ll have a greater reduction of SV. Therefore, use vasodilators to decrease afterload.
Mean dose – 3.8 tablets a day (1 tablet = 37.5 mg hydralazine/20 mg nitrates)
Acute Decompensated Heart Failure Tx
Drug
IV Diuretics
Oxygen
MOA
Treatments and Pharmacodynamics
SE / Contraindications
- Pts w/ significant fluid overload should be treated promptly.
- If pts are receiving too much, the initial IV dose should equal or exceed their chronic daily dose.
- Urine output and signs/symptoms of congestion should be serially assessed and dose adjusted
accordingly to relieve symptoms, reduce volume excess, and avoid hypotension.
Previously not on diuretics:
Furosemide 20-40 mg IV and then titrate. Adequate response within 2 hrs. – double the dose. Pts w/
renal dysfunction may need larger dose.
Already on chronic diuretics: double the oral dose.
Continuous dosing: furosemide drip at 10 mg/hr  240 mg/IV daily
Additionally, may use thiazide diuretics, ultrafiltration, hemodialysis, or augment CO to improve
renal function.
Titrate to keep patient comfortable – keep oxygen sat > 90 %
Non-invasive ventilation:
- CPAP or Bopp
- Provides positive end-expiratory pressure
- Used in pts w/ respiratory distress (pulm edema), respiratory acidosis, persistent hypoxia
- Improves oxygenation
- Decreases need for mechanical ventilation
Vasodilators (IV)
- Use if urgent need for afterload reduction or refractory heart failure and low CO. Adjunct to diuretic therapy!
- Reduce LV filling pressure, acts as venodilator
Nitroglycerin
- High doses can decrease systemic vascular resistance (afterload)
(nitrate)
- IV medication – can titrate quickly
Nitroprusside
(nitrate)
Nesiritide
(natriuretic
peptide)
- preferred agent
- balanced vasodilator and venodilator
- decreases LV filling pressure AND decreases systemic vascular resistance (afterload)
- afterload reduction improves LV Stroke Work
- balanced vasodilator and venodilator
- decreases LV filling pressure AND decreases systemic vascular resistance (afterload
- promotes natriuretic
- use w/ pts w/o hypotension or cardiogenic shock or who are symptomatic despite therapy
hypotension, headache
hypotension, metabolism produces
cyanide which can limit use
hypotension and risk of worsening renal
function
Inotropes (IV)
- Bridge therapy for end stage HF patients who are awaiting definitive therapy or surgery (transplant, LVAD, etc)
- Inotropes can improve symptoms but does not improve mortality. Increases atrial and ventricular arrhythmias.
PDE (-)
- Increases inotropy by inhibiting breakdown of cAMP
Milrinone
- Reduce systemic and pulmonic vascular resistance
- Improve LV diastolic compliance
- Increases CO, Decreases afterload, decrease filling pressures
B1 receptor
- Increases SV and CO
Dobutamine
agonist
- Modest decrease in systemic vascular resistance and filling pressures
Hypotension