Heart failure, acute vasodilators

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. 

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). 

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. 

Vasodilators are effective in acute heart failure because they provide a reduction in preload (through venodilation), or reduction in afterload (through arteriolar dilation), or both. Some evidence suggests that long-term use of hydralazine and isosorbide dinitrate can also reduce damaging remodeling of the heart. 

Venodilators Releases nitric oxide (NO) activates guanylyl cyclase (see Chapter 12) Venodilation reduces preload and ventricular stretch Acute and chronic heart failure angina Oral 4-6 h duration Toxicity Postural hypotension, tachycardia, headache Interactions Additive with other vasodilators and synergistic with phosphodiesterase type 5 inhibitors... 

Inamrinone, milrinone Phosphodiesterase type 3 inhibitors decrease cAMP breakdown Vasodilators lower peripheral vascular resistance also increase cardiac contractility Acute decompensated heart failure IV only duration 3-6 h Toxicity Arrhythmias Interactions Additive with other arrhythmogenic agents... 

Elkayam U et al Vasodilators in the management of acute heart failure. Crit Care Med 2008 36 S95. 

In addition to these traditional vasodilators, nesir-itide (Natrecor) was developed as a newer method for producing arterial and venous dilation in people with heart failure.58 This substance was derived from human B-type natriuretic peptide (BNP) using recombinant DNA techniques. BNP is a naturally occurring substance that is released from the ventricles when the heart is subjected to increased blood volume and pressure.12 This substance dilates peripheral arteries and veins, thus reducing cardiac afterload and preload, respectively. Hence, nesiritide can be administered intravenously to reduce cardiac workload in certain patients with severe or acute heart failure.12,58... 

The drugs most commonly used in chronic heart failure are diuretics, ACE inhibitors, angiotensin receptor antagonists, and U-blockers (Table 13-1). In acute failure, diuretics and vasodilators play important roles. 

P-Adrenergic stimulation improves cardiac performance by positive inotropic effects and vasodilation. Dobutamine (see p. 66) is the most commonly used inotropic agent other than digitalis. Dobutamine leads to an increase in intracellular cAMP, which results in the activation of protein kinase. Slow calcium channels are one important site of phosphorylation by protein kinase. When phospho-rylated, the entry of calcium ion into the myocardial cells increases, thus enhancing contraction (Figure 16.11). Dobutamine must be given by intravenous infusion, and is primarily used in the treatment of acute heart failure in a hospital setting. 

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. 

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. 

Acute severe congestive failure with pulmonary edema often requires a vasodilator that reduces intravascular pressures in the lungs. Furosemide has such vasodilating actions in the context of acute failure. Minoxidil would decrease arterial pressure and increase the heart rate excessively. Spironolactone is useful in chronic failure but not usually in acute pulmonary edema. The answer is (A). 

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