Hydralazine congestive heart failure

Minoxidil is a more potent vasodilator than hydralazine, and the compensatory increases in heart rate, cardiac output, renin release, and sodium retention are more dramatic. Severe sodium and water retention may precipitate congestive heart failure. Minoxidil also causes reversible hyper-... 

Unlabeled uses Hydralazine in doses up to 800 mg 3 times/day has been effective in reducing afterload in the treatment of congestive heart failure (CHF), severe aortic insufficiency, and after valve replacement. 

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. 

Hydralazine and dihydralazine are predominantly arterial vasodilators which cause a reduction in peripheral vascular resistance but also reflex tachycardia and fluid retention. They were used in the treatment of hypertension, in combination with a -blocker and a diuretic. Long-term use of these compounds may cause a condition resembling lupus erythematodes with arthrosis, dermatitis and LE-cells in the blood. This risk is enhanced in women and in patients with a slow acetylator pattern. When combined with the venous vasodilator isosorbide (an organic nitrate) hydralazine was shown to be mildly beneficial in patients with congestive heart failure (V-HEFT I Study). Hydralazine and dihydralazine have been replaced by other therapeutics, both in hypertension treatment and in the management of heart failure. 

Nitrates and hydralazine have been used in patients with congestive heart failure. An angiotensinconverting enzyme inhibitor such as lisinopril increases the left ventricular ejection fraction in... 

The CONSENSUS study was performed in 253 patients with severe congestive heart failure. They were randomized to receive either placebo (n = 126) or enalapril (n = 127), from 2.5 mg bid to 20 mg bid with a follow-up period that averaged 182 days. By the end of the study, there had been 68 deaths in the placebo group and 50 in the enalapril group (p =. 003) (313). Later, enalapril was shown to be superior to hydralazine-isosorbide dinitrate (314, 315). 

Dilation of venous blood vessels leads to a decrease in cardiac preload by increasing venous capacitance arterial dilators reduce systemic arteriolar resistance and decrease afterload. Nitrates (see p. 175) are commonly employed venous dilators for patients with congestive heart failure. If the patient is intolerant of ACE inhibitors, the combination of hydralazine and isosorbide dinitrate is most commonly used. Amlodipine and felodipine (see p. 188) have less negative inotropic effect than other calcium channel blockers, and seem to decrease sympathetic nervous activity. 

Hydralazine may cause a dose-related, reversible lupus-like syndrome, which is more common in slow acetylators. Lupus-like reactions can usually be avoided by using total daily doses of less than 200 mg. Other hydralazine side effects include dermatitis, drug fever, peripheral neuropathy, hepatitis, and vascular headaches. For these reasons, hydralazine has limited usefulness in the treatment of hypertension. However, it may be useful in patients with severe chronic kidney disease and in kidney failure. Minoxidil is a more potent vasodilator than hydralazine, and the compensatory increases in heart rate, cardiac output, renin release, and sodium retention are more dramatic. Severe sodium and water retention may precipitate congestive heart failure. Minoxidil also causes reversible hyper-... 

Nitrates are the drugs of choice in patients with left ventricular impairment, in whom they are of benefit when used in combination with hydralazine (3), and they should be used in preference to the calcium antagonists, which cause deterioration in myocardial function by an as yet unknown mechanism (4). In black patients with congestive heart failure taking ACE inhibitors and beta-block-ers, a combination of isosorbide dinitrate plus hydralazine significantly reduced total mortality (5). 

Acute decreases in renal function and hyperkalemia usually resolve over several days after ACEl or ARB therapy is discontinued. Occasional patients will require management of severe hyperkalemia, usually with sodium polystyrene sulfate (see Chap. 50). ACEl or ARB therapy may frequently be reinitiated, particularly for patients with congestive heart failure, after intravascular volume depletion has been corrected or the diuretic doses reduced. The development of mild renal insufficiency (serum creatinine concentration of 2 to 3 mg/dL) may be an acceptable trade-off for hemodynamic improvement in certain patients with severe congestive heart failure or renovascular disease not amenable to invasive management. Congestive heart failure patients with greater renal insufficiency may be best treated by substitution of hydralazine and nitrates for afterload reduction. 

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. 

An experimental study in 8 patients with congestive heart failure found that when they were given either sodium nitroprusside hy infusion (7 to 425 micrograms/minute) or hydralazine hy intravenous injection (5 mg every 10 to 20 minutes to a total dose of 10 to 60 mg) the total renal digoxin clearance was increased by about 50% by both drugs and the serum digoxin levels were decreased by 20% by the nitroprusside and 11% by the hydralazine. ... 

Most side effects associated with hydralazine administration are due to vasodilation and the reflex hemodynamic changes that occur in response to vasodilation. These side effects include headache, flushing, nasal congestion, tachycardia, and palpitations. More serious manifestations include myocardial ischemia and heart failure. These untoward effects of hydralazine are greatly attenuated when the drug is administered in conjunction with a (3-blocker. 

The oral bioavailability and pharmacokinetics of hydralazine are not altered significantly by heart failure unless there is severe hepatic congestion or hypoperfusion. Intravenous hydralazine provides little practical advantage over oral formulations except for urgent use during pregnancy, a state in which relative or absolute contraindications exist for most other vasodilators. 

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