Other drugs used in congestive heart failure

The major agents used with or as alternatives to digitalis in heart failure include diuretics, ACE inhibitors, b₁-selective sympathomimetics, phosphodiesterase inhibitors, and vasodilators.

A. Diuretics: Diuretics are often used in congestive heart failure before digitalis and other drugs are considered. Furosemide is a very useful agent for immediate reduction of the pulmonary congestion and severe edema associated with acute congestive heart failure or severe chronic failure. Thiazides such as hydrochlorothiazide are often used in the management of mild chronic failure. The pharmacologic characteristics of the diuretics are discussed in Chapter 15.

B. Angiotensin-Converting Enzyme Inhibitors: These agents have been shown to be as effective as digitalis—or more so—in the management of chronic heart failure. Although they have no direct positive inotropic action, ACE inhibitors reduce aldosterone secretion, salt and water retention, and vascular resistance. They reduce symptoms and are the only drugs that have been shown to prolong life in patients with heart failure. Along with diuretics and digitalis, they are now considered among the first-line drugs for chronic heart failure.

C. Beta-Selective Adrenoceptor Agonists: Dobutamine and dopamine are useful in some cases of acute failure. However, they are not appropriate for chronic failure because of tolerance, lack of oral efficacy, and significant arrhythmogenic effects.

D. Phosphodiesterase Inhibitors: Amrinone and milrinone are the major representatives of this infrequently used group, though theophylline (in the form of its salt, aminophylline) was commonly used in the past. These drugs increase cAMP by inhibiting its breakdown by phosphodiesterase and cause an increase in cardiac intracellular calcium similar to that produced by beta-adrenoceptor agonists. Phosphodiesterase inhibitors also cause vasodilation, which may be responsible for a major part of their beneficial effect. At very high concentrations, these agents may also increase the sensitivity of the contractile protein system to calcium (site 6 in Figure 13-3).

E. Vasodilators: Vasodilator therapy with nitroprusside or nitroglycerin is often used for acute severe congestive failure. The use of these vasodilator drugs is based on the reduction in cardiac size and improved efficiency that can be realized with proper adjustment of venous return and reduction of resistance to ventricular ejection. Vasodilator therapy can be dramatically effective, especially in cases in which excessive afterload is a major factor in causing the failure (eg, continuing hypertension in an individual who has just had an infarct). Chronic congestive heart failure sometimes responds favorably to oral vasodilators such as hydralazine or isosorbide dinitrate.

Drug list

The following drugs are important members of the group discussed in this chapter. Prototypes should be learned in detail; features of the major variants should be known well enough so that the variants can be distinguished from the prototypes and from each other; the other significant agents should be recognized as belonging to a specific subclass.

Subclass	Prototype	Major Variants	Other Significant Agents
Cardiac glycosides	Digoxin	Digitoxin	Ouabain
Positive inotropic digitalis substitutes	Dobutamine, Amrinone		Milrinone, theophylline
ACE inhibitors	Captopril		Enalapril, lisinopril
Diuretics	Furosemide, hydrochlorothiazide
Vasodilators	Nitroprusside	Nitroglycerin, hydralazine	Isosorbide dinitrate, theophylline

Cardiac Glycosides & Congestive Heart Failure