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Back to main menu: ESC Back to last screen: left arrow Back to Table of Contents 4. Digitalis and Other Positive Inotropic Drugs Used in Congestive Heart Failure BG Katzung & WW Parmley 旼컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴 I. Introduction 1. Pathophysiology and Mechanisms 2. Drug Selection II. Digitalis 1. Properties 2. Adverse effects 3. Drugs available III. Other positive inotropic agents 1. Properties 2. Drugs available Subsets of acute severe congestive heart failure 읕컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴컴 (PgDn key for more text) INTRODUCTION In congestive heart failure, cardiac output is inadequate for the needs of the body. Many of the signs and symptoms of the disease result from attempts by the body to correct or compensate for the inadequate peripheral perfusion. Some of these compensatory responses lead to fur- ther deterioration of cardiac function as described under pathophysiol- ogy. The positive inotropic agents are described in this chapter. Other drug groups are briefly reviewed here but are covered in more detail in other chapters. Therapeutic Rationale * Reduce salt and water retention: Diuretics are the first line drugs for use in most uncomplicated cases of congestive heart failure. (Restriction of sodium intake is desirable but sometimes difficult to achieve.) Reduction of blood volume decreases the size of the heart, allowing it to function on a more favorable portion of the ventricular function curve, and reduces the intracapillary pressure that leads to edema. The diuretics are described in more detail in Chapter 13. (PgDn key for more text) * Increase the force of cardiac contraction: Positive inotropic drugs such as digitalis glycosides are effective in many cases of chronic failure and move the heart to a higher ventricular function curve. They are generally more toxic than the diuretics. Several positive in- otropic substitutes for digitalis are available for use in special circumstances. * Reduce vascular tone: Vasodilators reduce the work of the heart and improve cardiac ejection and tissue perfusion. They are especially useful in acute failure, eg, that associated with myocar- dial infarction and severe hypertension. Vasodilators are described in greater detail in Chapters 2 and 5. Mechanisms * Diuretics: The mechanisms by which these drugs act are discussed in Chapter 6. Their efficacy in congestive heart failure reflects the magnitude of the salt retention that occurs in failure. * Positive inotropic drugs: - Digitalis glycosides: Digitalis drugs act by inhibiting membraneNa,K- ATPase, thereby causing an increase in intracellular sodium. In- creased intracellular sodium results in an increase in in tracellular calcium. The latter ion directly modulates the contractile process. (PgDn key for more text) - Sympathomimetics: Beta-1 adrenoceptor stimulants such as dobutamine and dopamine are valuable in some cases of acute failure since they increase cardiac contractility and cause some vasodilation. In favor- able cases, increased contractility is not accompanied by significant tachycardia. - Amrinone, milrinone, methylxanthines, and other PDE inhibitors: These drugs cause an increase in cylic AMP by inhibiting cardiac phosphodiesterase. The increase in cAMP results in an increase in transmembrane calcium flux and a secondary increase in cardiac con tractility. The same biochemical action increases cAMP in vascular smooth muscle and results in vasodilation. * Vasodilators: Direct-acting agents (eg, nitrates, nitroprusside), sympathoplegics (eg, prazosin), and angiotensin converting enzyme in- hibitors (eg, captopril) reduce cardiac workload and increase cardiac output in failure associated with high vascular pressures. Captopril also decreases aldosterone levels, thereby reducing salt and water retention. (PgDn key for more text) Major indications * Chronic low output failure: Use an thiazide diuretic , digoxin , and if necessary, a vasodilator combination such as hydralazine (unlabelled use) and isosorbide dinitrate , or captopril . Some patients respond better to captopril than to digoxin as the second line drug. * Acute, severe failure: See Table . Other Indications: * Cardiac arrhythmias: cardiac glycosides are often used in atrial tachycardias, atrial flutter, and atrial fibrillation to control ventricular rate. In the case of flutter and fibrillation, glycosides may also lead to the conversion of the arrhythmia to normal sinus rhythm. References: 1. Arnold SB, et al: Long-term digitalis therapy improves left ventricular function in heart failure. NEJM 1980; 303:1443. 2. Cohn JN (editor): New concepts in the mechanisms and treatment of congestive heart failure (Symposium). Am J Cardiol 1985; 55: 1A. (PgDn key for more references) 3. Cohn JN, et al: Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative study. NEJM 1986; 314: 1547. 4. Digitalis. (Symposium) J Am Coll Cardiol 1985; 5: 1A. 5. Doherty JE: Clinical use of digitalis glycosides. An update. Cardiol- ogy 1985; 72:225. 6. Franciosa JA, Dunkman WB, Leddy CL: Hemodynamic effects of vasodilators and long-term response in heart failure. J Am Coll Car- diol 1984; 3: 1521. 7. Jaski BE, et al: Positive inotropic and vasodilator actions of mil- rinone in patients with severe congestive heart failure. Dose response relationships and comparison to nitroprusside. J Clin Invest 1085; 75: 643. 8. Maekawa K, Liang C-S, Hood WB: Comparison of dobutamine and dopamine in acute myocardial infarction. Effects of systemic hemodynamics, plasma catecholamines, blood flows and infarct size. Circulation 1983; 67:750. 9. Smith TW, et al: Digitalis glycosides: Mechanisms and manifestations of toxicity. (in 3 parts) Prog Cardiovasc Dis 1984; 26:413,495; 27:21. (Home to return to top of file)


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