Vasodilators heart failure

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

Direct Vasodilators Isosorbide dinitrate 20 mg and hydralazine 37.5 (BiDil) 1-2 tablets three times a day Minoxidil (Loniten) Hydralazine Heart failure (isosorbide dinitrate + hydralazine in African-Americans) A-HeFT66 Edema (minoxidil) Tachycardia Lupus-like syndrome (hydralazine) ... 

Treatment of acute heart failure targets relief of congestion and optimization of cardiac output utilizing oral or intravenous diuretics, intravenous vasodilators, and when appropriate, inotropes. 

Carson, R, Ziesche, S., Johnson, G. et al. (1999). Racial differences in response to therapy for heart failure analysis of the vasodilator-heart failure trials. /. Card. Pail., 5, 178-87. 

Dobutamine (76), on the other hand, is a dopamine derivative which does not act centrally, but is of interest because of its coronary vasodilator properties. Such drugs are potentially of value in treatment of angina pectoralis. Further, it is now undergoing extensive clinical trials as an inotropic agent for use in heart failure. Its synthesis is effected by Raney nickel catalyzed reduction of methyl p-methoxyvinylphenylketone (75) to its dihydro analog followed by reductive alkylation with p-(3,4-dimethoxyphenyl)ethylamine. The ether groups are cleaved with HBr to complete the synthesis of... 

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. 

The vascular endothelium produces a number of substances that are released basally into the blood vessel wall to alter vascular smooth muscle tone. One such substance is endothelin (ET-1). Endothelin exerts its effects throughout the body, causing vasoconstriction as well as positive inotropic and chronotropic effects on the heart. The resulting increases in TPR and CO contribute to an increase in MAP. Synthesis of endothelin appears to be enhanced by many stimuli, including Ag II, vasopressin, and the mechanical stress of blood flow on the endothelium. Synthesis is inhibited by vasodilator substances such as prostacyclin, nitric oxide, and atrial natriuretic peptide. There is evidence that endothelin is involved with the pathophysiology of many cardiovascular diseases, including hypertension, heart failure, and myocardial infarction. Endothelin receptor antagonists are currently available for research use only. 

FIGURE 8-2. General treatment algorithm for acute decompensated heart failure (ADHF) based on clinical presentation. IV vasodilators that may be used include nitroglycerin, nesiritide, or nitroprusside. Metolazone or spironolactone may be added if the patient fails to respond to loop diuretics and a second diuretic is required. IV inotropes that may be used include dobutamine or milrinone. (D/C, discontinue HF, heart failure SBP, systolic blood pressure.) (Reprinted and adapted from J Cardiac Fail, Vol 12, pages el-el 22, copyright 2006, with permission from Elsevier.)... 

Starting doses of ACE inhibitors should be low with slow dose titration. Acute hypotension may occur at the onset of ACE inhibitor therapy, especially in patients who are sodium- or volume-depleted, in heart failure exacerbation, very elderly, or on concurrent vasodilators or diuretics. Patients with these risk factors should start with half the normal dose followed by slow dose titration (e.g., 6-week intervals). 

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-... 

Fluid retention may occur, perhaps as a result of peripheral vasodilation and/or improved insulin sensitization with a resultant increase in renal sodium and water retention. A dilutional anemia may result, which does not require treatment. Edema is reported in 4% to 5% of patients when glitazones are used alone or with other oral agents. When used in combination with insulin, the incidence of edema is about 15%. Glitazones are contraindicated in patients with New York Heart Association Class III and IV heart failure and should be used with great caution in patients with Class I or II heart failure or other underlying cardiac disease. 

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. 

Advise patients that initiation of treatment and (to a lesser extent) dosage increases may be associated with transient symptoms of dizziness or lightheadedness (and rarely syncope) within the first hour after dosing. Thus, during these periods, avoid situations such as driving or hazardous tasks, where symptoms could result in injury. In addition, vasodilatory symptoms often do not require treatment, but it may be useful to separate the time of dosing of carvedilol from that of the ACE inhibitor or to temporarily reduce the dose of the ACE inhibitor. Do not increase the dose of carvedilol until symptoms of worsening heart failure or vasodilation have been established. 

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. 

ACE-inhibition will cause a reduction of cardiac afterload and preload in patients with heart failure. In addition, the ACE-inhibitors exert a favourable effect on the neuro-endocrine activation process associated with chronic heart failure. They are more effective than classic vasodilators such as hydralazine and isosorbide, which do not influence these neuroendocrine mechanisms in a favourable manner. 

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. 

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. 

Alpha-adrenoceptor antagonists are used as antihypertensives and to reduce afterload in the treatment of heart failure. Urapidil and, to a lesser extent, ketanserin are used in the treatment of essential hypertension and acute perioperative hypertension. In contrast to other vasodilators urapidil does not increase intracranial pressure when given intravenously, making it preferable for use in neurosurgical interventions. The effects of the excessive catecholamine concentrations in patients with phaeochromocytoma can be treated by the non-selective ol- and o2-adrenoceptor antagonists phentolamine or phenoxybenzamine. 

Chapter 12 Vasodilators the Treatment of Angina Pectoris Chapter 13 Drugs Used in Heart Failure Chapter 14 Agents Used in Cardiac Arrhythmias Chapter 15 Diuretic Agents... 

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