Drugs affecting the
cardiovascular system
Treatment of
congestive heart failure CHF
I- Overview of
congestive heart failure CHF
it is a condition in
which the heart is unable to pump sufficient blood to meet the needs of the
body
it can be caused by
impaired ability of
the cardiac muscle to contract
an increesed work load
imposed on the heart
CHF is accompanied by
abnormal increase in blood volume and interstitial fluid
the heart,veins,and
capillaries therefore generally dilated with blood.Hence,the term (Congestive)
heart failure
Underlying causes of
CHF
arteriosclerotic heart
disease
dilated cardiomyopathy
congential heart
disease
valvular heart disease
left systolic
dysfunction secondary to coronary artery disease is the most common cause of
CHF
The therapeutic goal
for CHF is to increase cardiac output
Three classes of drugs
have been shown to be clinically effective
in reducing symptoms and prolonging life
Vasodilators: reduce
the load on the myocardium
Diuretic agents
: decease extracellular fluid volume
Inotropic agents
: increase the strength of contraction of
cardiac muscle
these agents
relieve the symptomps
of cardiac insufficiency
do not reverse the
underlying pathologic condition
Drugs that may
preciptate or exacerbate CHF so should be
avoided as possble
non steroidal
antiinflammatory drugs
alcohol
B blockers
calcium ghannel blockers
some antiarrythmic
drugs
II- Vasodilators
In CHF,the impaired
contractile function of the heart is exacerbated by compensatory increase in
preload and afterload
Preload
the volume of blood
that fills the ventricle during diastole
elevated preload
causes overfilling of the heart which increases the work load
Afterload
the pressure that must
overcome for the heart to pump blood into the arterial system
elevated afterload
cause the heart to work harder to pump
blood into the
arterial system
Vasodilators are
useful in reducing excessive preload and afterload as follow
dilation of veinous
blood vessels increases the venous capacitance by which a decrease in preload
occurs
arterial dilators
reduce systemic arteriolar resistance by which a decrease in afterload occurs
Classes of
vasodilators
A- Angiotensin
convertizing enzyme (ACE) inhibitors
ex : captopril -
lisinopril - enalapril
Adverse effects
postural hypotension
renal insuffeciency
persistant dry cough
should not be used in
pregnant women
B - Direct smooth
muscle relaxants
ex: hydrazaline -
isosorbide - sodium nitroprusside
III - Diuretics
ex : bumetanide -
furosemide - hydrochlorothiazide
relieve pulmonary
congestion and peripheral edema
useful in reducing the
symptoms of volume overload
Thiazide diuretics are
relatively mild diuretics and lose efficacy if patient creatinine clearance is
less than 50 ml/min
Loop diuretics are
used in patients with renal insuffiency
Overdoses of loop
diuretics can lead to profound hypovolemia
IV- Inotropic agents
positive inotropic
agents enhance cardiac muscle contractility
and increase cardiac
output
although these drugs act by different mechanisms ,in
each case the inotropic action is the result of an increased cytoplasmic calcium
concentration that
enhances the contractility of the cardiac muscle
A-Cardiac
glycosides(Digitalis)=digoxin &digitoxin
digoxin(lanoxin) is
the most widely used agent
Therapeutic uses
digoxin is indicated in patients with severe left
ventricular systolic dysfunction after initiation of diuretic and vasodilation
therapy
not indicated in
patient with diastolic or right sided heart failure
patients with mild to moderate heart failure will often
respond to treatment with ACE inhibitors and diuretics and do not require digoxin
N.B.
The digitalis
glycosides show only a small difference between a therapeutically effective dose and doses that are toxic or even
fatal i.e.
have low therapeutic index
Factors predisposing to
digitalis toxicity
a) Electrolytic
disturbances
hypokalemia can
preciptate serious arrythmia
reduction of serum K
levels is most frequently observed in patients receiving thiazide or loop
diuretics
hypokalemia can be
usually prevented by use of a K sparing diuretics or supplementation with
potassium chloride
hypercalcemia and
hypomagnesemia also predispose to digitalis toxicity
b)Drugs
Quinidine : can cause
digitalis toxicity by
displacing digitalis
from plasma protein binding sites
competing with
digitalis for renal excretion
Verpamil(isoptin)
: displace digitalis
from( PPBS) and can increase digoxin levels by 50 to 75% which may require a reduction in the dose of digoxin
c)Others
potassium depleting
diuretics
corticosteroids
hypothyrodism
hypoxia
renal failure
myocarditis
B- B adrenergic agonists
ex : dobutamine
improves cardiac
performance by both
positive inotropic
effects
vasodilation
must be given by I.V.
infusion and is primarily used in the
treatment of acute
heart failure in hospital setting
C- Phosphodiesterase
inhibitors : not used clinically