Presentation on theme: "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."— Presentation transcript:
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.
These drugs block phosphodiesterase in cardiac and smooth muscle which prevents the hydrolysis of cAMP.
An increase in cAMP leads to an increase in Ca 2+.
Phosphodiesterase inhibitors have 2 primary actions: 1. Increasing the force of contraction (similar to the cardiac glycosides) 2. vasodilation
They are generally used for only 2-3 days because they may produce potentially serious adverse effects (ventricular arrhythmias, severe hypotension, thrombocytopenia)
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 Selective beta blockers target beta 1 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.
They decrease both the heart rate and the force of contraction.
At first this appears to be the opposite of the effects needed in 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.
Beta blockers slow the heart rate, which allows the heart to both fill and function more effectively.
Beta blockers used in the treatment of heart failure include: acebutolol: (Sectral) atenolol (Tenormin) bisoprolol (Zebeta) esmolol (Brevibloc)
The “preferred” beta blockers for the treatment of heart failure are: carvedilol (Coreg) metoprolol (Lopressor)
3. Vasodilator therapy of heart failure Vasodilators generally play a minor role in the drug therapy of heart failure.
They are used in those unresponsive to the “more conventional treatments”.
They act directly on vascular smooth muscle to relax blood vessels and lower blood pressure.
They reduce the symptoms of heart failure by decreasing cardiac oxygen demand.
Vasodilators indicated for the treatment of heart failure include: hydralazine (Apresoline): acts on smooth muscle of arterioles, increases heart rate and cardiac output
isosorbide dinitrate (Isordil, Sorbitrate): causes venodilation, particularly in the larger veins and vena cava
This reduces both venous return to the heart and preload, allowing the heart to pump more forcefully.
Adverse effects include dizziness, headache, hypotension and tachycardia.
4. Diuretic therapy of heart failure Diuretics are one of the “more conventional” treatments for heart failure.
Diuretic therapy, as well as sodium restriction is recommended for patients with mild heart failure
The main effect produced by the diuretics is elimination of excess water, Na 1+
Diuretics relieve the symptoms of heart failure by lowering blood volume and reducing edema.
They reduce fluid overload and lower blood pressure which reduces the workload on the heart and increases cardiac output.
Diuretics produce few side effects and are often used in combination with ACE inhibitors.
To control mild heart failure in patients with normal kidney function: chlorothiazide (Diuril) or hydrochlorothiazide (Hydrodiuril) methylclothiazide (Enduron, Aquatensen)
For patients with more advanced heart failure, low kidney function, and/or more severe edema: furosemide (Lasix) bumetanide (Bumex) torsemide (Demadex)
Some studies have shown that treatment of heart failure with a potassium sparing diuretic reduces mortality.
These diuretics are more effective when the aldosterone level is elevated as they are either:
competitive inhibitors of the aldosterone receptor, or decrease aldosterone activity by blocking Na 1+ channels in the collecting ducts
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 ACE inhibitors have become the preferred drugs for the treatment of heart failure.
They inhibit angiotensin II. Angiotensin II causes vasoconstriction, and release of aldosterone and ADH.
ACEI action promotes vasodilation and excretion of H 2 O and Na 1+
In addition, they decrease the inactivation of an endogenous vasodilator, bradykinin.
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 Natriuretic peptide was approved in 2001 for the treatment of heart failure.
It is a small peptide hormone structurally identical to a hormone secreted by the heart, beta-type natriuretic peptide (hBNP)
When heart failure occurs, the ventricles secrete hBNP in response to the increased stretching of the ventricular walls.
hBNP acts on the kidney, increasing excretion of Na 1+ and water, thus lowering blood pressure.
hBNP also causes vasodilation (which contributes to reduced preload).
The natriuretic peptide which has been approved for the treatment of heart failure is nesiritide (Natrecor).
It is approved only for severe heart failure because of the potentially serious side effects: apnea, hypotension, arrhythmias.