Drugs for treating heart failure
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Drugs for treating heart failure. A. Introduction. Heart failure (HF) is due to the inability of the ventricles to pump sufficient blood thru-out the body. There are a number of causes of heart failure:. diabetes. from:http://www.nhlbi.nih.gov/health/dci/images/heart_coronary_artery.gif.

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Drugs for treating heart failure

Drugs for treating heart failure


A introduction

A. Introduction

  • Heart failure (HF) is due to the inability of the ventricles to pump sufficient blood thru-out the body.


Drugs for treating heart failure

  • There are a number of causes of heart failure:


Drugs for treating heart failure

  • diabetes


From http www nhlbi nih gov health dci images heart coronary artery gif

from:http://www.nhlbi.nih.gov/health/dci/images/heart_coronary_artery.gif

  • coronary artery disease


Drugs for treating heart failure

  • chronic HT


Drugs for treating heart failure

  • MI


Drugs for treating heart failure

  • mitral stenosis (inability of mitral valve to open fully)


Drugs for treating heart failure

  • The incidence of heart failure increases with increasing age.


Drugs for treating heart failure

  • About 20% of patients diagnosed with heart failure die within 1 year of diagnosis, about 50% die within 5 years.


Drugs for treating heart failure

  • There is NO cure for heart failure. Treatment goals involve treating/removing the underlying causes in order to improve the quality of life and/or extend life expectancy.


B pathophysiology of heart failure

B. Pathophysiology of heart failure

  • Two important factors which affect cardiac output, and therefore affect how heart failure is treated, are preload and afterload


1 preload

1. Preload

  • Immediately before the chambers of the heart contract they are filled to their maximum capacity with blood.


Drugs for treating heart failure

  • The degree to which heart fibers are stretched prior to contraction is known as preload.


Drugs for treating heart failure

  • The more these fibers are stretched, the more forcefully they will contract


2 afterload

2. Afterload

  • For the left ventricle to pump blood out of the heart, it must overcome a fairly substantial pressure in the aorta.


Drugs for treating heart failure

  • Afterload is the pressure in the aorta that must be overcome for blood to be ejected from the left side of the heart.


Drugs for treating heart failure

  • In heart failure, the heart becomes weakened and cannot eject all the blood it receives.


Drugs for treating heart failure

  • This weakening can occur on the right side, on the left side or on both sides.


3 left heart failure aka chf

3. Left heart failure aka CHF

  • If heart failure is on the left side (more common), excess blood accumulates in the left ventricle.


Drugs for treating heart failure

  • The wall of the left ventricle becomes thicker in an attempt to compensate for this extra blood.


Drugs for treating heart failure

  • It can only compensate so much, then the blood “backs up” into the lungs.


Drugs for treating heart failure

  • This results in classic symptoms: cough, shortness of breath, especially when a patient is prone


4 right heart failure

4. Right heart failure

  • Here, blood “backs up” into peripheral veins.


Drugs for treating heart failure

  • This results in classic symptoms: swelling of feet, ankles (peripheral edema) and engorgement of organs such as liver


5 cardiac output

5. Cardiac Output

  • Cardiac output (the amount of blood pumped by the heart per minute) is significantly decreased during heart failure.


Drugs for treating heart failure

  • This results in an inability of the cardiovascular system to meet the body’s demands for oxygen.


Drugs for treating heart failure

  • Patients with heart failure experience constant fatigue.


C drug class mechanisms of action in treating heart failure

C. Drug class mechanisms of action in treating heart failure

  • There are a number of different mechanisms of action when considering how to treat heart failure:


Drugs for treating heart failure

  • 1. Certain drugs increase the force of contraction. This is called a positive inotropic effect and is characteristic of:

  • a. cardiac glycosides

  • b. phosphodiesterase inhibitors


Drugs for treating heart failure

  • 2. Certain drugs decrease the heart rate. This is characteristic of the adrenergic (beta) blockers.


Drugs for treating heart failure

  • 3. Certain drugs relax vascular smooth muscle which dilates blood vessels and lowers blood pressure. This is characteristic of the vasodilators.


Drugs for treating heart failure

  • 4. Certain drugs reduce blood volume. This is characteristic of the diuretics.


Drugs for treating heart failure

  • 5. Certain drugs affect the renin-angiotensin-aldosterone (RAA) system. This is characteristic of the ACE inhibitors


Drugs for treating heart failure

  • 6. Certain drugs reduce both preload and afterload. This is characteristic of the natriuretic peptides.


1a cardiac glycoside therapy of heart failure

1a. Cardiac glycoside therapy of heart failure

  • The cardiac glycosides are derived from the foxglove plants, Digitalis purpurea and

    Digitalis lanata


Drugs for treating heart failure

  • They have been used to treat heart disorders for over 2000 years, and were

    the mainstay of heart failure treatment until the discovery of the ACE inhibitors


Drugs for treating heart failure

  • Cardiac glycosides have 2 primary actions:

  • 1. Increasing the force of contraction allows the heart to eject more blood per beat which increases cardiac output and improves circulation.


Drugs for treating heart failure

  • 2. reduction in heart rate


Drugs for treating heart failure

  • Digoxin stimulates the vagus nerve, which slows the activity of the sinoatrial (SA) and atrioventricular (AV) nodes


Drugs for treating heart failure

  • This reduced heart rate (known as a negative chronotropic effect) is seen as a lengthening of the PR interval on an ECG.


Drugs for treating heart failure

  • The specific mechanism of action of the cardiac glycosides is inhibition of the

    Na1+- K1+-ATPase pump.


Drugs for treating heart failure

  • This pump normally removes Na1+ from the cell and brings K1+ in.


Drugs for treating heart failure

  • Inhibition of the pump leads to an accumulation of Na1+ inside heart muscle cells


Drugs for treating heart failure

  • The increased concentration of Na1+ stimulates the Na1+-Ca2+ exchange mechanism, leading to an increase in intracellular Ca2+.


Drugs for treating heart failure

  • Elevated Ca2+ results in an increase in the force of heart contraction


Drugs for treating heart failure

  • The primary cardiac glycoside available in the U.S. is digoxin (Digitek, Lanoxicaps, Lanoxin).


Drugs for treating heart failure

  • It’s ½ life is between 1-2 days, longer in older patients (those mostly likely to be taking it).


Drugs for treating heart failure

  • The antidote for digoxin is called digoxin immune fab (Digibind). It binds digoxin and has a rapid onset of action, less than 1 minute after IV infusion.


Drugs for treating heart failure

  • It is necessary to have an antidote available as nearly 1/3 of patients taking cardiac glycosides develop symptoms of toxicity.


Drugs for treating heart failure

  • There is a very narrow margin between a therapeutic dose and a toxic dose.


Drugs for treating heart failure

  • Symptoms of toxicity: pulse rate below 60 beats/min., confusion, nausea, diarrhea, yellow-green halos around lights, hallucinations


Drugs for treating heart failure

  • Vincent van Gogh’s “The Starry Night” (1889) is believed, by some physicians, to show evidence of digoxin (aka digitalis) toxicity, in the way he created yellow-green halos around the stars.


1b phosphodiesterase inhibitor therapy of heart failure

1b. Phosphodiesterase inhibitor therapy of heart failure

  • Phosphodiesterase inhibitors are used for short-term control of acute/advanced heart failure that is unresponsive to the “more conventional” ( i.e. diuretics and ACE inhibitors) treatments.


Drugs for treating heart failure

  • These drugs block phosphodiesterase in cardiac and smooth muscle which prevents the hydrolysis of cAMP.


Drugs for treating heart failure

  • An increase in cAMP leads to an increase in Ca2+.


Drugs for treating heart failure

  • Phosphodiesterase inhibitors have 2 primary actions:

  • 1. Increasing the force of contraction (similar to the cardiac glycosides)

  • 2. vasodilation


Drugs for treating heart failure

  • They are generally used for only 2-3 days because they may produce potentially serious adverse effects (ventricular arrhythmias, severe hypotension, thrombocytopenia)


Drugs for treating heart failure

  • Phosphodiesterase inhibitors include:

  • inamrinone (Inocor): IV, peak effect in 10 min.

  • milrinone (Primacor): IV, peak effect in 2 min.


2 beta adrenergic blocker therapy of heart failure

2. Beta adrenergic blocker therapy of heart failure

  • Selective beta blockers target beta1 receptors in the heart and kidneys. They are used in combination with other drugs to slow the progression of heart failure and to prolong patient survival.


Drugs for treating heart failure

  • They decrease both the heart rate and the force of contraction.


Drugs for treating heart failure

  • At first this appears to be the opposite of the effects needed in treating heart failure.


Drugs for treating heart failure

  • However, there is increased activation of the sympathetic nervous system in patients with heart failure that causes tachycardia and increases stress on the heart.


Drugs for treating heart failure

  • Beta blockers slow the heart rate, which allows the heart to both fill and function more effectively.


Drugs for treating heart failure

  • Beta blockers used in the treatment of heart failure include:

  • acebutolol: (Sectral)

  • atenolol (Tenormin)

  • bisoprolol (Zebeta)

  • esmolol (Brevibloc)


Drugs for treating heart failure

  • The “preferred” beta blockers for the treatment of heart failure are:

  • carvedilol (Coreg)

  • metoprolol (Lopressor)


3 vasodilator therapy of heart failure

3. Vasodilator therapy of heart failure

  • Vasodilators generally play a minor role in the drug therapy of heart failure.


Drugs for treating heart failure

  • They are used in those unresponsive to the “more conventional treatments”.


Drugs for treating heart failure

  • They act directly on vascular smooth muscle to relax blood vessels and lower blood pressure.


Drugs for treating heart failure

  • They reduce the symptoms of heart failure by decreasingcardiac oxygen demand.


Drugs for treating heart failure

  • Vasodilators indicated for the treatment of heart failure include:

  • hydralazine (Apresoline): acts on smooth muscle of arterioles, increases heart rate and cardiac output


Drugs for treating heart failure

  • isosorbide dinitrate (Isordil, Sorbitrate): causes venodilation, particularly in the larger veins and vena cava


Drugs for treating heart failure

  • This reduces both venous return to the heart and preload, allowing the heart to pump more forcefully.


Drugs for treating heart failure

  • Adverse effects include dizziness, headache, hypotension and tachycardia.


4 diuretic therapy of heart failure

4. Diuretic therapy of heart failure

  • Diuretics are one of the “more conventional” treatments for heart failure.


Drugs for treating heart failure

  • Diuretic therapy, as well as sodium restriction is recommended for patients with mild heart failure


Drugs for treating heart failure

  • The main effect produced by the diuretics is elimination of excess water, Na1+


Drugs for treating heart failure

  • Diuretics relieve the symptoms of heart failure by lowering blood volume and reducing edema.


Drugs for treating heart failure

  • They reduce fluid overload and lower blood pressure which reduces the workload on the heart and increases cardiac output.


Drugs for treating heart failure

  • Diuretics produce few side effects and are often used in combination with ACE inhibitors.


Drugs for treating heart failure

  • To control mild heart failure in patients with normal kidney function:

  • chlorothiazide (Diuril) or hydrochlorothiazide (Hydrodiuril)

  • methylclothiazide (Enduron, Aquatensen)


Drugs for treating heart failure

  • For patients with more advanced heart failure, low kidney function, and/or more severe edema:

  • furosemide (Lasix)

  • bumetanide (Bumex)

  • torsemide (Demadex)


Drugs for treating heart failure

  • Some studies have shown that treatment of heart failure with a potassium sparing diuretic reduces mortality.


Drugs for treating heart failure

  • These diuretics are more effective when the aldosterone level is elevated as they are either:


Drugs for treating heart failure

  • competitive inhibitors of the aldosterone receptor, or

  • decrease aldosterone activity by blocking Na1+ channels in the collecting ducts


Drugs for treating heart failure

  • Potassium sparing diuretics used in the treatment of heart failure include:

  • spironolactone (Aldactone)

  • eplerenone (Indira)

  • amiloride (Midamor)

  • triamterene (Dyrenium)


5 ace inhibitor acei therapy of hf

5. ACE inhibitor (ACEI) therapy of HF

  • ACE inhibitors have become the preferred drugs for the treatment of heart failure.


Drugs for treating heart failure

  • They inhibit angiotensin II. Angiotensin II causes vasoconstriction, and release of aldosterone and ADH.


Drugs for treating heart failure

  • ACEI action promotes vasodilation and excretion of H2O and Na1+


Drugs for treating heart failure

  • In addition, they decrease the inactivation of an endogenous vasodilator, bradykinin.


Drugs for treating heart failure

  • ACE inhibitors which have been approved by the FDA in the treatment of heart failure include:

  • captopril (capoten)

  • enalapril maleate (Vasotec)

  • fosinopril (Monopril)

  • lisinopril (Prinivil, Zestril)

  • quinapril (Accupril)

  • ramipril (Altace)


6 natriuretic peptide therapy of hf

6. Natriuretic peptide therapy of HF

  • Natriuretic peptide was approved in 2001 for the treatment of heart failure.


Drugs for treating heart failure

  • It is a small peptide hormone structurally identical to a hormone secreted by the heart, beta-type natriuretic peptide (hBNP)


Drugs for treating heart failure

  • When heart failure occurs, the ventricles secrete hBNP in response to the increased stretching of the ventricular walls.


Drugs for treating heart failure

  • hBNP acts on the kidney, increasing excretion of Na1+ and water, thus lowering blood pressure.


Drugs for treating heart failure

  • hBNP also causes vasodilation (which contributes to reduced preload).


Drugs for treating heart failure

  • The natriuretic peptide which has been approved for the treatment of heart failure is nesiritide (Natrecor).


Drugs for treating heart failure

  • It is approved only for severe heart failure because of the potentially serious side effects: apnea, hypotension, arrhythmias.


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