Drugs affecting the cardiovascular system

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