Heart failure, chronic isosorbide dinitrate

Cohn IN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure, [see comment]. N. Engl. J. Med. 1991 325 303-10. 

Elkayam U, AminJ, Mehra A, VasquezJ, Weber L, Rahimtoola SH. A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure, Circulation 1990 82 1954-1961. 

In eight patients with chronic heart failure taking digoxin 0.25 mg/day, isosorbide dinitrate 10 mg tds caused only a small increase in (15%) and had no effect on the mean steady-state serum concentration or AUC (241). 

Mahgoub AA, El-Medany AH, Abdnlatif AS. A comparison between the effects of diltiazem and isosorbide dinitrate on digoxin pharmacodynamics and kinetics in the treatment of patients with chronic ischemic heart failure. Saudi Med J 2002 23(6) 725-31. 

Severe postural hypotension has been observed in patients given both isosorbide dinitrate and hydralazine for chronic heart failure (26), although this has not been a problem in large studies (90). 

Massie B, Kramer B, Haughom F. Postural hypotension and tachycardia during hydralazine-isosorbide dinitrate therapy for chronic heart failure. Circulatiou 1981 63(3) 658-64. 

One side effect unique to hydralazine is a dose-dependent drug-induced lupus-like syndrome. Hydralazine is eliminated by hepatic A-acetyltransferase. This enzyme displays genetic polymorphism, and slow acetylators are especially prone to develop drug-induced lupus with hydralazine. This syndrome is more common in women and is reversible on discontinuation. Drug-induced lupus may be avoided by using less than 200 mg hydralazine daily. Other side effects of hydralazine include dermatitis, drug fever, peripheral neuropathy, hepatitis, and vascular headaches. For these reasons, hydralazine has limited usefulness in the treatment of hypertension. However, it is still used with isosorbide dinitrate in patients with heart failure (especially African-Americans) and is useful in patients with severe chronic kidney disease and kidney failure. 

F. 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 increased 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. 

In a crossover study in 8 patients with chronic heart failure given digoxin 250 micrograms daily for 20 days with isosorbide dinitrate 10 mg three times daily for the last 10 days, there was no change in the mean steady-state concentration, AUC or half-life of digoxin. ... 

No significant adverse events or interactions were reported in a study of Cs-4 in patients with chronic heart failure. Patients were administered 3 to 4 g daily of Cs-4 in addition to their standard prescription medication which included digoxin, hydrochlorothiazide, isosorbide dinitrate, furosemide, lanatoside, dopamine, and dobutamine (Zhang et al. 1995). 

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