Congestive heart failure vasodilators

Hypertension, or a chronic elevation in blood pressure, is a major risk factor for coronary artery disease congestive heart failure stroke kidney failure and retinopathy. An important cause of hypertension is excessive vascular smooth muscle tone or vasoconstriction. Prazosin, an aradrenergic receptor antagonist, is very effective in management of hypertension. Because oq-receptor stimulation causes vasoconstriction, drugs that block these receptors result in vasodilation and a decrease in blood pressure. 

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-... 

The pharmacological mechanisms of action of NO donors that contribute to their benefit in coronary artery disease, congestive heart failure, and hypertension are listed in Table 11.1. These actions can be grouped into five categories vasodilation, decrease in myocardial oxygen consumption, improvement in hemodynamic performance,... 

The most salient pathophysiological features of congestive heart failure (CHF) are diminution of ventricular contractility and profound, sympathetically mediated vasoconstriction. Agents with both peripheral vasodilating [24] and positive inotropic [25] activities ameliorate the symptoms of CHF. 

The discovery of the positive inotropic and systemic vasodilator activities of bipyridine-derived compounds, like amrinone (7) and milrinone (8), has markedly stimulated research aimed at the development of structurally related non-steroidal, non-catecholamine cardiotonics. In this context, a wide variety of pyridazinone derivatives have been prepared and investigated in search for novel agents useful for the chronic management of congestive heart failure. 

Mention should also be made of the possibility of affecting cardiac function in angina pectoris (p. 306) or congestive heart failure (p. 132) by reducing venous return, peripheral resistance, or both, with the aid of vasodilators and by reducing sympathetic drive applying 3-blockers. 

Congestive heart failure treatment may be improved by cautiously adding a /3-blocker to conventional management with ACE-inhibitors and diuretics. Bisoprolol and carvedilol are the preferable /3-blockers, since their beneficial effect has been convincngly demonstrated in appropriate clinical trials. Bisoprolol is a highly selective /8i-blocker. Carvedilol has additional properties to its /8-receptor blocking activity, such as a weak vasodilator component and anti-oxidant activity. The beneficial effect is very likely to be caused by /8i-adrenoceptor blockade. 

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. 

Cilostazol is a selective cAMP phosphodiesterase inhibitor. It inhibits platelet aggregation and is a direct arterial vasodilator. It is used for the symptoms of intermittent claudication in individuals with peripheral vascular disease. Side-effects of cilostazol include headache, diarrhea, increased heart rate, and palpitations. Drugs similar to cilostazol have increased the risk of death in patients with congestive heart failure. 

Cohn IN et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure Results of a Veterans Administration Cooperative Study. N Engl J Med 1986 314 1547-1552. 

Prazosin [MinipressJ. Prazosin is a competitive alpha-1 antagonist that has emerged as one of the primary alpha-1 selective agents. It tends to produce vasodilation in both arteries and veins, and is used primarily in the long-term management of essential hypertension.38 Prazosin has also been used to reduce alpha-1 receptor mediated activity in congestive heart failure, Raynaud phenomenon, pheochromocytoma, and BPH. Prazosin is administered orally. 

FIGURE 35.7 Fenoldopam, which causes vasodilation, is useful in congestive heart failure. 

In addition, a vasodilator in combination with an angiotensin-converting enzyme inhibitor has been used in congestive heart failure. The vasodilators may be classified as venodilators, arterial dilators, or balanced-type vasodilators. 

The rationale for vasodilation in the management of congestive heart failure is based on the increased arteriolar vasotone that occurs. This initiates a vicious circle in which cardiac function is further depressed by an increase in afterload and in resistance to ejection (Figure 35.9). 

Possible uses. Arteriolar vasodilators are given to lower blood pressure in hypertension (p.314), to reduce cardiac work in angina pectoris (p.318), and to reduce ventricular afterload (pressure load) in cardiac failure (p.322). Venous vasodilators are used to reduce venous filling pressure (preload) in angina pectoris (p. 318) or congestive heart failure (p.322). Practical uses are indicated for each drug group. 

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-... 

Cogan JJ, Humphreys MH, Carlson CJ, Benowitz NL, Rapaport E. Acute vasodilator therapy increases renal clearance of digoxin in patients with congestive heart failure. Circulation 1981 64(5) 973-6. 

Kereiakes D, Chatterjee K, Parmley WW, Atherton B, Curran D, Kereiakes A, Spangenberg R. Intravenous and oral MDL 17043 (a new inotrope-vasodilator agent) in congestive heart failure hemodynamic and clinical evaluation in 38 patients. I Am Coll Cardiol I984 4(5) 884-9. 

Cesario D, Clark J, Marsel A. Beneficial effects of intermittent home administration of the inotrope/vasodilator milrinone in patients with end-stage congestive heart failure a preliminary study. Am Heart J 1998 135(l) 121-9. 

Jaski BE, Filer MA, Wright RF, Braunwald E, Colucci WS. Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside. J Clin Invest 1985 75(2) 643-9. 

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