Nesiritide

Because renal vasodilatation and hyperfiltration are often associated with a natriuretic response, a number of activators or inhibitors of endogenous vasoactive systems can cause increased NaCl excretion, and some of these may be developed into compounds of clinical interest in special situations. Such agents include natriuretic pqDtides most notably B-type natriuretic peptide (nesiritide), neutral endopeptidase (NEP) inhibitors (thiorphan, phosphoramidon), mixed NEP and ACE inhibitors (omapatrilat), guanylin and uroguanylin, kinins, prostaglandins of the E series, adrenomedullin, relaxin, prolactin, and others. 

In theory, one could utilise GC-A ligands to lower blood pressure and to reduce blood volume as they increase the excretion of water and salt. Nesiritide, human recombinant BNP, is the first member of this new class of drugs approved for the initial intravenous treatment of acutely decompensated congestive heart failure. Whether nesiritide can be a valuable addition to the standard therapy of decompensated heart failure remains to be demonstrated. 

Add nitroprusside or nesiritide if Cl <2.2 L/min/m2 and clinical end point not achieved despite therapeutic dobutamine +/- milrinone... 

Nesiritide—2 mcg/kg IV bolus followed by a continuous IV infusion of 0.01 mcg/kg/min. Doses above the initial infusion rate should be limited to carefully selected patients. High-alert medication—read package insert before use... 

The current values for ruling out a cardiac etiology for dyspnea are a BNP less than 100 pg/mL (100 ng/L) or an NT-proBNP less than 300 pg/mL (300 ng/L or 35.4 pmol/L). BNP measurements require cautious interpretation, as numerous conditions can also elevate BNP concentrations. These include older age, renal dysfunction, pulmonary embolism, and chronic pulmonary disease. Nesiritide, a recombinant BNP drug, has an identical structure to native BNP and will interfere with the commercial BNP assay, resulting in a falsely elevated level. Therefore, blood for BNP determination should be obtained 2 hours after the end of a nesiritide infusion, or alternatively the NT-proBNP assay should be utilized. 

Nesiritide Bolus 2 mcg/kg Infusion 0.01 mcg/kg per minute BP, HR, urinary output and kidney function, blood BNP concentrations... 

Nesiritide has been shown to improve symptoms of dyspnea and fatigue. In a randomized clinical trial, the safety and efficacy of adding nesiritide to standard care was compared to placebo and nitroglycerin.53 Nesiritide was found to significantly decrease PCWP more than nitroglycerin and placebo over 3 hours. Nesiritide improved patients self-reported... 

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.)... 

Nesiritide is manufactured using recombinant techniques and is identical to the endogenous B-type natriuretic peptide secreted by the ventricular myocardium in response to volume overload. Consequently, nesiritide mimics the vasodilatory and natriuretic actions of the endogenous peptide, resulting in venous and arterial vasodilation increases in cardiac output natriuresis and diuresis and decreased cardiac filling pressures, sympathetic nervous system activity, and renin-angiotensin-aldosterone system activity. 

The precise role of nesiritide in the pharmacotherapy of decompensated HF remains controversial. Compared to nitroglycerin, it appears to produce little improvement in clinical outcomes and is substantially more expensive. Two recent metaanalyses suggest an increased risk of worsening renal function as well as an increase in mortality with nesiritide. A prospective randomized trial is being conducted to clarify the safety and efficacy of nesiritide. 

Nesiritide - recombinant B-type natriuretic Heart failure... 

Inamrinone (Inocor) Milrinone (Primacor) Nesiritide (Natrecor)... 

Nesiritide is not a cure for CHF but it will help relieve symptoms... 

Nesiritide Activates BNP receptors, increases cGMP Vasodilation diuresis Acute decompensated failure IV only duration 18 minutes Toxicity Renal damage, hypotension... 

Nesiritide Agonist of natriuretic peptide receptors Increased sodium and water excretion t vasodilation Heart failure1... 

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... 

A synthetic form of the endogenous peptide brain natriuretic peptide (BNP) has recently been approved for use in acute cardiac failure as nesiritide. This recombinant product increases cGMP in smooth muscle cells and effectively reduces venous and arteriolar tone in experimental preparations. It also causes diuresis. The peptide has a short half-life of about 18 minutes and is administered as a bolus intravenous dose followed by continuous infusion. Excessive hypotension is the most common adverse effect. Measurement of endogenous BNP has been proposed as a diagnostic test because plasma concentrations rise in most patients with heart failure. 

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