Nesiritide

Nesiritide is a drug given intravenously (IV) for short-term treatment of congestive heart failure (CHF). It is used to treat sudden worsening of CHF symptoms. It was approved by the Food and Drug Administration in 2001 and is now marketed as Natrecor by Scios (a Johnson & Johnson company). Nesiritide is a synthetic version of a naturally-occurring hormone called B-type natriuretic peptide. As such, it dramatically increases excretion of sodium in the urine, a phenomenon known as natriuresis. Use of the drug in less-severely ill patients declined after reports of an increased risk of kidney damage and death. Discussion continues as to the appropriate role of nesiritide in clinical practice.

This is an x-ray of a 28-year-old woman with congestive heart failure. The enlarged cardiac silhouette in this woman, which is characteristic of heart failure, was cause by long-term high blood pressure. Source:CDC

Other Names

Nesiritide is sometimes referred to as Brain Natriuretic Peptide, or B-Type Natriuretic Peptide (BNP), which is the hormone it mimics in the body.

Uses

Nesiritide is used to treat sudden exacerbation of CHF symptoms. These symptoms include shortness of breath during minimal activity (known as acutely decompensated CHF).

How Nesiritide Is Taken

The recommended regimen is based on the patient's body weight; the usual dose is a bolus (starting) dose of 2 micrograms of the drug per kg of body weight, followed by an infusion of 0.01 micrograms per kg per minute over several hours. Pulmonary pressure monitoring can detect whether the drug is working. Appropriate monitoring usually requires a special catheter known as a Swan-Ganz catheter that must be threaded through the heart and through the pulmonary artery on its way to the lungs, and this limits the use of nesiritide to hospital settings.^[1]

How Nesiritide Works

Nesiritide stimulates an enzyme in the cells that line blood vessels and other tissues in the body. It acts like a BNP hormone. In the kidneys, it causes excretion of sodium and water. It relaxes muscles in blood vessel walls, allowing them to dilate (vasodilation). Finally, it inhibits the release of renin and aldosterone, which are two hormones that promote fluid and sodium retention. Overall, these effects reduce fluid retention and blood pressure, as well as allow the heart to work more efficiently.^[2]

How the Body Affects Nesiritide

In patients with CHF, the half-life of nesiritide, or the time needed for the concentrations of the drug in the blood to be reduced by half, is approximately 18 minutes. Nesiritide is degraded and its components recycled in the cells that it acts upon, and some is excreted in the urine.

Side Effects

Nesiritide can produce side effects in multiple systems of the body:

• Cardiovascular
  • hypotension
  • arrhythmia
  • chest pain (angina)

• central nervous system
  • headache
  • insomnia
  • dizziness
  • anxiety
  • confusion
  • abnormal sensations
  • tremor

• Other systems
  • nausea and vomiting
  • abdominal pain
  • back pain
  • leg cramps

Risks and Precautions

Nesiritide may cause severe and prolonged hypotension. This risk is reduced if blood pressure is monitored while nesiritide is being given, and if the drug is used only in people with systolic blood pressure higher than 90 mm Hg. The risk of severe low blood pressure is increased in people who cannot tolerate other drugs that dilate blood vessels (vasodilators).

The use of nesiritide in people with low cardiac filling pressures, which occur when the heart fills with blood, is generally avoided.

Some trials have shown that nesiritide reduces kidney function, but complete kidney failure was not seen.

Drug Interactions

Coadministration of nesiritide with angiotensin converting enzyme (ACE) inhibitors (e.g., captopril (Capoten)) may cause unsafe drops in blood pressure.

Nesiritide can react physically with many other drugs that are given by injection. These interactions are characterized by changes in the physical properties of nesiritide or the drug with which it is given. These changes can reduce its effectiveness, or cause toxicity. Drugs that can interact physically with nesiritide include the following:

• bumetanide (Bumex)
• enalaprilat
• ethacrynate (Edecrin)
• furosemide(Lasix)
• hydralazine (Apresoline)
• heparin
• insulin

In general, these drugs are not given at the same time as nesiritide.

History

In 1988, Scios discovered a natural human peptide (protein fragment) called human B-type natriuretic peptide (hBNP) that is normally produced by the heart. Nesiritide, marketed as Natrecor, is a recombinant form of the natural human peptide, hBNP. The introduction of Natrecor in 2001 marked an important advancement in the understanding and treatment of acute heart failure.

Controversy

Off-label use of nesiritide as a chronic treatment for patients not hospitalized was called into question by studies published in 2005 suggesting that the drug could contribute to kidney problems and an increased risk of death.^[3][4] Rapid "de-adoption" of the drug followed,^[5] and Johnson & Johnson’s product marketing practices were investigated by federal authorities.

The appropriate role of nesiritide in clinical practice has been discussed.^[6]

Clinical Trials

This pivotal trial, published in 2000, concluded that nesiritide was useful in the treatment of decompensated CHF.^[7] In this trial, 60%–70% of patients had significantly improved symptoms compared to only 14% of patients treated with a placebo. Check for clinical trials here

Interesting Facts

• The discovery that the heart contained the hormone BNP was the first realization that the heart, so well-known as a muscular pump, also released hormones. Because it releases hormones, the heart is properly regarded as a member of both the endocrine system and the cardiovascular system.^[8]

• Since BNP is normally produced by the heart and released into the circulation, its blood concentration can be measured. Serum levels of BNP are sometimes used in diagnosing cardiovascular diseases.^[9]

References

1. ↑ Nicholls MG, Richards AM; Christchurch Cardioendocrine Research Group. Disease monitoring of patients with chronic heart failure. Heart. 2007 Apr;93(4):519-23. Citation
2. ↑ Prahash A, Lynch T. B-type natriuretic peptide: a diagnostic, prognostic, and therapeutic tool in heart failure. Am J Crit Care. 2004 Jan;13(1):46-53; quiz 54-5. Review. Erratum in: Am J Crit Care. 2004 Mar;13(2):101. Abstract | Full Text | PDF
3. ↑ Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation. 2005 Mar 29;111(12):1487-91. Abstract | Full Text | PDF
4. ↑ Sackner-Bernstein JD, Kowalski M, Fox M, Aaronson K. Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA. 2005 Apr 20;293(15):1900-5. Abstract | Full Text | PDF
5. ↑ Hauptman PJ, Schnitzler MA, Swindle J, Burroughs TE. Use of nesiritide before and after publications suggesting drug-related risks in patients with acute decompensated heart failure. JAMA. 2006 Oct 18;296(15):1877-84. Abstract | Full Text | PDF
6. ↑ Sharp A, Mayet J. The utility of BNP in clinical practice. J Renin Angiotensin Aldosterone Syst. 2004 Jun;5(2):53-8. Abstract | PDF
7. ↑ Colucci WS, Elkayam U, Horton DP, et al. Intravenous nesiritide, a natriuretic peptide, is used in the treatment of decompensated congestive heart failure. Nesiritide Study Group. N Engl J Med. 2000 Jul 27;343(4):246-53. Abstract | Full Text | PDF
8. ↑ Goetze JP. Biochemistry of pro-B-type natriuretic peptide-derived peptides: the endocrine heart revisited. Clin Chem. 2004 Sep;50(9):1503-10. Abstract | Full Text | PDF
9. ↑ Burke MA, Cotts WG. Interpretation of B-type natriuretic peptide in cardiac disease and other comorbid conditions. Heart Fail Rev. 2007 Mar;12(1):23-36. Abstract

External Links

Natrecor.com, the drug's official website

Scios website