CHAPTER 46 DRUGS FOR HEART FAILURE

Heart failure (HF) is a serious, progressive disorder characterized by ventricular

dysfunction, reduced cardiac output,
insufficient tissue perfusion, and signs of fluid retention.
- commonly referred to as congestive heart failure
- causes fluid accumulation (congestion) in the lungs and peripheral tissues
- principal drugs employed for treatment are angiotensin-converting enzyme
(ACE) inhibitors, diuretics, beta
blockers, and digoxin

I. PATHOPHYSIOLOGY OF HEART FAILURE

- syndrome is characterized by signs of inadequate tissue perfusion
(fatigue, shortness of breath,
exercise intolerance) and/or signs of volume overload
- major underlying causes of HF are chronic hypertension and myocardial
infarction
- other causes include valvular disease, coronary artery disease,
congenital heart disease, dysrhthmias,
and aging of the myocardium
- HF is a chronic disorder that requires continuous treatment with drugs

A. SIGNS SYMPTOMS
AND
- decreased tissue perfusion results in reduced exercise tolerance, fatigue,
and shortness of breath
- shortness of breath may also stem from pulmonary edema
- increased sympathetic tone produces tachycardia
- increased ventricular filling, reduced systolic ejection, and myocardial
hypertrophy result in
cardiomegaly (increased heart size)
- combination of increased venous tone plus increased blood volume helps
cause pulmonary edema,
peripheral edema, hepatomegaly (increased liver size) and
distention of the jugular veins
- weight gain results from fluid retention

II. OVERVIEW OF DRUGS USED TO TREAT HEART FAILURE

A. ACE INHIBITORS AND OTHER VASODILATORS

B. ARBS

C. DIURETICS
- first line drugs for all patients with signs of volume overload (or with a
history of volume overload)
 - by reducing blood volume, can decrease venous pressure, arterial
pressure (afterload), pulmonary
edema, peripheral edema, and cardiac dilation
- excessive diuretics is hazardous and must be avoided

1. Thiazide Diuretics – hydrochorothiazide

- produce moderate diuresis
- oral agents used for long-term therapy of HR when edema is
not too great
- cannot be used if cardiac output is greatly reduced
-principal adverse effect is hypokalemia which increases the
risk of digoxin-induced
dysrhythmias

2. High-Ceiling (Loop) Diuretics – furosemide

- produce profound diuresis
- can promote fluid loss even when GFR is low
- preferred to thiazides when cardiac output is greatly reduced
- administration may be oral or IV
- drug of choice for patients with severe HF
- can cause hypokalemia, increasing the risk of digoxin toxicity
- can cause severe hypotension secondary to excessive
volume reduction

3. Potassium-Sparing Diuretics – spironolactone, triamterene

- promote only scant diuresis
- employed to counteract potassium loss caused by thiazide
and loop diuretics,
lowering the risk of digoxin-induced dysrhythmias

- principal adverse effect is hyperkalemia

- caution is need if combined with ACE inhibitors
- spironlactone prolongs survival in patients with HF primarily
by blocking receptors for
aldosterone, not by causing diuresis

D. BETA BLOCKERS
- names end in “ol”
- carvedilol, metoprolol, and bisoprolol
- when added to conventional therapy can improve left ventricular
(LV) ejection fraction,
increase exercise tolerance, slow progression of HF, reduce the need
for hospitalization, and,
most importantly, prolong survival
- mechanism underlying benefits possibly include protecting the heart
from excessive sympathetic
stimulation and protecting against dysrhythmias
- full benefits may not be seen for 1 – 3 months
 - principal adverse effects are: fluid retention and worsening of HF
fatigue
hypotension
bradycardia or heart block
- carvedilol (Coreg) and metoprolol (Lopressor, Toprol XL) are the only beta
blockers approved

E. INOTROPIC AGENTS
- drugs that increase the force of myocardial contraction
- given to improve performance of the failing heart
- type available: cardiac glycosides, sympathomimetics, and
phophodiesterase (PDE) inhibitors
- sympathomimetics and PDE inhibitors currently available must be
administered by IV infusion
- use is generally restricted to acute care of hospitalized patients

1. Cardiac Glycosides – digoxin

- used widely for long-term therapy
- do not prolong life
- cardiac glycosides are the only intropic agents that can be
taken orally, therefore,
suited for long-term therapy

2. Sympathomimetic Drugs: Dopamine and Dobutamine

a. Dopamine – intropin
- can activate: beta1-adrenergic receptors in the heart
– increases heart rate,
creating a risk of tachycardia
dopamine receptors in the kidney – dilates
renal blood
vessels, increasing renal blood flow
and urine output
at high doses, alpha1-adrenergic receptors in
blood vessels –
increases vascular resistance
(afterload), reducing
cardiac output
- administered by continuous infusion
- constant monitoring of BP, electrocardiogram
(EKG) and urine output
is required
- employed as a short-term rescue measure for
severe, acute cardiac
failure

b. Dobutamine – dobutrex
- causes selective activation of beta1-adrenergic
receptors
 - can increase myocardial contractility, improving cardiac
performance
- can cause tachycardia
- does not activate alpha1 receptors, therefore, does not
increase vascular
resistance
- generally preferred to dopamine for short-term
treatment of acute HF
- administered by continuous infusion

e. Phosphodiesterase (PDE) Inhibitors

Inamrinone – inocor
- called an inodilator because it increases
myocardial contractility and
promotes vasodilation
- increased contractility results from intracellular
accumulation of cyclic
AMP secondary to inhibition of PDE-3
(enzyme that normally
degrades cAMP)
- improvements in cardiac function elicited by
amrinone are superior to
those elicited by dopamine or dobutamine
- administered by IV infusion
- not suited for outpatient use
- only for short-term treatment
- should be protected from light and should not be
mixed with glucose
containing solutions

F. SPIRONOLACTONE: ALDOSTERONE RECEPTOR BLOCKER

- aldactone
- can reduce symptoms, decrease hospitalization, and prolong life in
moderate to severe HF
- helps HF by blocking receptors for aldosterone
- benefits in HF do not result primarily from diuresis and potassium
retention, instead they result from
blockade of receptors for aldosterone, primarily in the heart and
blood vessels

Aldosterone’s Harmful Effects:

• promotion of myocardial remodeling (which impairs pumping)
• promotion of myocardial fibrosis (which increases the risk of
dysrhythmias)
• activation of the sympathetic nervous system and suppression of
norepinephrine uptake in the heart (both of which can promote
dysrhythmias and ischemia)
• promotion of vascular fibrosis (which decreases arterial compliance)
 • promotion of baroreceptors dysfunction
- spironolactone blocks aldosterone actions
- when added to regimen, residual effects are nearly eliminated
- adverse effects gynecomastia – breast enlargement, which develops in
men
- is cosmetically troublesome and painful
- is caused by blocking receptors for testosterone
hyperkalemia – caused by decreasing renal excretion of
potassium
- potassium levels should be monitored

III. CARDIAC (DIGITALIS) GLYCOSIDES

- naturally occurring compounds (and one of the most dangerous) that
have profound effects on the
mechanical and electrical properties of the heart
- by improving mechanical function of the heart, can reduce symptoms of
HF
- by altering electrical properties of the heart, can suppress dysrhythmias –
or cause them
- toxicity results from the drug’s propensity to cause dysrhythmias
- these drugs are used with respect, caution and skill

A. DIGOXIN
- lanoxin, lanoxicaps, digitek are indicated for HF and dysrhythmias
- patient telemetry must be monitored
- for HF, can reduce symptoms, increase exercise tolerance, and decease
hospitalization
- does not prolong life
- when used by women, it may actually shorten the life span

1. Digoxin’s Mechanical Effects on the Heart

- exerts a positive inotropic action - - increases the force of
ventricular contraction, increasing
cardiac output

2. Digoxin’s Adminstration – therapeutic range is 0.5 – 1.1 ng/ml (levels

above 2.0 ng/ml are toxic)
- can be administered orally and intravenously
- intramuscular administration causes severe pain and tissue
damage – should be avoided
- prior to administration, the rate and regularity of the heart beat
should be determined
- if heart rate is less than 60 beats/min or if a change in
rhythm is detected – DO NOT
ADMINISTER and call the physician
- cardiac status should be monitored continuously for 1 – 2 hours
IV. MANAGEMENT OF HEART FAILURE

A. STAGE A
- no symptoms of HF
- no structural or functional cardiac abnormalities
- do have behaviors or conditions strongly associated with developing HF
- associated factors: hypertension
diabetes
coronary artery disease
family history of cardiomyopathy
personal history of alcohol abuse, rheumatic fever,
or treatment with a
cardiotoxic drug
- should cease behaviors that cause HF risk, especially smoking and
alcohol abuse
B. STAGE B
- no signs or symptoms of HF
- structural heart disease that is strongly associated with development of
HF
- changes include: LV hypertrophy or fibrosis
LV dilation or hypocontractility
valvular heart disease
previous myocardial infarction
- goal is to prevent development of symptomatic HF
- approach is to implement measures that can prevent further cardiac
injury, retarding the progression of
remodeling and LV dysfunction
- specific measures include all for Stage A and treatment with an ACE
inhibitor plus a beta blocker for all
patients with a reduced ejection fraction, history of myocardial
infarction or both

C. STAGE C
- symptoms of HF - - including dyspnea, fatigue, peripheral edema, and
distention of the jugular vein
- structural heart disease

Treatment Goals: relief of pulmonary and peripheral congestive symptoms

improvement of functional capacity and quality of life
slowing of cardiac remodeling and progression of LV
dysfunction
prolongation of life

Drug Therapy: Diuretics, ACE inhibitors, Beta Blockers, Digoxin

Drugs to Avoid: antidysrhythmic agents, calcium channel blockers,

NSAIDs

D. STAGE D
 - have advanced structural heart disease and marked symptoms of HF at
rest, despite treatment with
maximal doses of medications used in Stage C
- best long-term solution is a heart transplant
- management focuses largely on control of fluid retention
- intake and output should be monitored closely
- should weigh every day
- patients should not be discharged until a stable and effective oral diuretic
regimen has been
established